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A substrate has or is provided on a surface with a first porosity. A dispersion with low-viscosity liquid is applied to the surface in order to form a ceramic layer with a second porosity having preferably larger and/or more pores than in the first porosity. The liquid has the ability to be sucked by capillary force into the first pore formation and, in a first stage, to retain on the surface material and/or liquid particles which do not penetrate into this first pore formation, and which contribute to the continued construction of the layer. In a second stage, the substrate is subjected to sintering in which the particles finally forming the layer are held together with intermediate spaces which consist of or are included in the second porosity, the spaces being formed either by the fact that material and liquid particles separate from the particles finally forming the layer are driven off during the sintering and/or by the fact that the particles forming the layer are chosen with a particle size which means that the last-mentioned particles are held together after the sintering despite the intermediate spaces. The invention also relates to an arrangement. By means of the invention, a dental product can be provided with excellent porosity which is advantageous in connection with dental installations.
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Sorafenib is the standard of care for the palliative treatment of HCC. The recommended dose of sorafenib in patients with HCC is 400 mg twice daily. Sorafenib dose-limiting toxicities include diarrhea, arterial hypertension and hand-foot syndrome. Owing a large inter-patient variability (near 50%) of sorafenib Area Under the Curve (AUC) over 12h, an over-exposure to sorafenib could explain acute toxicity. On the other hand, a suboptimal exposure could result in an insufficient anti-tumor activity as suggested by a recent study. This inter-patient variability of sorafenib pharmacokinetic is especially relevant in HCC. Indeed, most of HCC are developed on cirrhotic liver with often an impaired liver function, a decrease of albuminemia and sometimes ascitis. All these parameters are likely to impact the sorafenib pharmacokinetic. The aim of this pilot study is to correlate the sorafenib plasma concentration to observed toxicity and to the disease control rate in 100 patients.
The dose of sorafenib will be the recommended dose: 400 mg twice daily. Sorafenib daily doses will be only adjusted by the clinician on adverse event. Values of sorafenib AUC will not be transmitted to clinician.
Patients will be followed during 12 months with 5 visits: Week 4, Week 8, Week 16, Month 6 and Month 12. Adverse event related to sorafenib will be recorded and graded according to the NCI-CTC for Adverse Event during all the study period. Sorafenib plasma concentrations will be assessed at 4, 8 and 16 weeks. An additional dosage could be performed between W1 and W4, before dose modification, if a dose modification is necessary due to adverse events before W4.
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In two randomized placebo-controlled trials of 2 years duration in patients with mild cognitive impairment (MCI), a total of 13 patients on galantamine (n=1026) and 1 patient on placebo (n=1022) died. The deaths were due to various causes which could be expected in an elderly population; about half of the galantamine deaths appeared to result from various vascular causes (myocardial infarction, stroke, and sudden death).
Although the difference in mortality between galantamine- and placebo-treated groups in these two studies was significant, the results are highly discrepant with other studies of galantamine. Specifically, in these two MCI studies, the mortality rate in the placebo-treated patients was markedly lower than the rate in placebo-treated patients in trials of galantamine in Alzheimer’s disease or other dementias (0.7 per 1000 person years compared to 22 to 61 per 1000 person years, respectively). Although the mortality rate in the galantamine-treated MCI patients was also lower than that observed in galantamine-treated patients in Alzheimer’s disease and other dementia trials (10.2 per 1000 person years compared to 23 to 31 per 1000 person years, respectively), the relative difference was much less. When the Alzheimer’s disease and other dementia studies were pooled (n=6000), the mortality rate in the placebo group numerically exceeded that in the galantamine group. Furthermore, in the MCI studies, no patients in the placebo group died after 6 months, a highly unexpected finding in this population.
Individuals with mild cognitive impairment demonstrate isolated memory impairment greater than expected for their age and education, but do not meet current diagnostic criteria for Alzheimer’s disease.
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Disclosed herein is a method and system for real-time health data management and prediction of health trends for patients. The system receives patient data from patients, doctors treating patients and one or more external sources. Upon receiving the patient data, system generates three tables for storing, general information, health information and preference information of patients. Thereafter, the system generates a distributed ledger in real-time for each patient based on details of each patient from three tables. The distributed ledger comprises consolidated health data from all the three tables. The system provides a selectively authorized access to the distributed ledger based on biometric information of the patient. Further, based on the consolidated health data, the system manages health data of each of the one or more patients and predicts health trends of each of the one or more patients using Artificial Intelligence (AI) Machine Learning (ML) techniques.
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The invention relates to a technique of filling an infusion bag with hydrogen and discloses a device for filling a medical infusion bag with hydrogen in a non-contact manner. The device comprises a hydrogen generator (1), a gas and liquid mixer (2), a positive displacement pump (3), a vane pump (4), an open water tank (8), a pressure regulation valve (10), and a sealed water tank (7). By means of the hydrogen generator, the solubility of the hydrogen is improved while any characteristic of water is not changed. The positive displacement pump and the vane pump are used, so the hydrogen is processed into micro-nanometer bubbles, the solubility of the hydrogen in water is greatly improved, and the dissolving time of the hydrogen is shortened. The invention further discloses a method for filling the medical infusion bag with the hydrogen in a non-contact manner. The method comprises the steps of mixing gas and liquid, dissolving the gas under high pressure and releasing the micro-nanometer hydrogen bubbles under low pressure. The solubility of the hydrogen is high, the consumed time is short, the production cost is saved, the purity of the product is improved, the content of impurities is reduced, it is guaranteed that bacteria and heat sources are avoided in the operation process, and accordingly clinical requirements for injection are met.
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BACKGROUND: Sepsis may be linked to oxidative stress and can be controlled by itaconate, an activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Nevertheless, the itaconate impact on sepsis-associated acute kidney injury (SA-AKI) has yet to be definitively established.
METHODS: We employed SA-AKI mouse model through a cecal ligation and puncture (CLP) procedure for the in vivo investigation of the potential nephroprotective effect of itaconate in this study. A plasmid was transfected into RAW264.7 cells to examine the Nrf2 pathway function after itaconate administration. Finally, the immune-responsive gene 1-knockout (IRG1-/-) mice were used to study the itaconate impacts on oxidative stress-induced SA-AKI.
RESULTS: We have shown that 4-octyl itaconate (OI) significantly reduced CD11b-positive macrophage aggregation and activated the Nrf2 pathway in the bone marrow-derived macrophages (BMDM). The impacts of Nrf2 inhibitor ML385 on the anti-inflammatory and antioxidant properties of itaconate were found to be partial. OI inhibited lipopolysaccharide-induced oxidative stress injury in RAW264.7 macrophages and activated Nrf2 in the nucleus to hinder the expression of nuclear factor kappa B p65, thereby suppressing oxidative stress injury in the macrophages. Additionally, the introduction of the transfected plasmid resulted in a partial inhibition of the anti-inflammatory impact of itaconate. The kidney injury caused by sepsis exhibited greater severity in the IRG1-/- mice than in the wild type mice. Exogenous OI partially attenuated the kidney injury induced by sepsis in the IRG1-/- mice and suppressed the oxidative stress injury in macrophages.
CONCLUSIONS: This investigation offers new proof to support the itaconate function in the development and progression of SA-AKI and shows a new possible therapeutic agent for the SA-AKI treatment.
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Immunosuppression increases the risk of nosocomial infection in patients with chronic critical illness. This exploratory study aimed to determine the immunometabolic signature associated with nosocomial infection during chronic critical illness. We prospectively recruited patients who were admitted to the respiratory care center and who had received mechanical ventilator support for more than 10 days in the intensive care unit. The study subjects were followed for the occurrence of nosocomial infection until 6 weeks after admission, hospital discharge, or death. The cytokine levels in the plasma samples were measured. Single-cell immunometabolic regulome profiling by mass cytometry, which analyzed 16 metabolic regulators in 21 immune subsets, was performed to identify immunometabolic features associated with the risk of nosocomial infection. During the study period, 37 patients were enrolled, and 16 patients (43.2%) developed nosocomial infection. Unsupervised immunologic clustering using multidimensional scaling and logistic regression analyses revealed that expression of nuclear respiratory factor 1 (NRF1) and carnitine palmitoyltransferase 1a (CPT1a), key regulators of mitochondrial biogenesis and fatty acid transport, respectively, in natural killer (NK) cells was significantly associated with nosocomial infection. Downregulated NRF1 and upregulated CPT1a were found in all subsets of NK cells from patients who developed a nosocomial infection. The risk of nosocomial infection is significantly correlated with the predictive score developed by selecting NK cell-specific features using an elastic net algorithm. Findings were further examined in an independent cohort of COVID-19-infected patients, and the results confirm that COVID-19-related mortality is significantly associated with mitochondria biogenesis and fatty acid oxidation pathways in NK cells. In conclusion, this study uncovers that NK cell-specific immunometabolic features are significantly associated with the occurrence and fatal outcomes of infection in critically ill population, and provides mechanistic insights into NK cell-specific immunity against microbial invasion in critical illness.
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Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome, and hyperglycemia. Monitor patients for these conditions with chronic use.
Corticosteroids can produce reversible hypothalamic-pituitary adrenal (HPA) axis suppression with the potential for corticosteroid insufficiency after withdrawal of treatment. Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. If the patient is receiving corticosteroids already, dosage may have to be increased.
Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently. Mineralocorticoid supplementation is of particular importance in infancy.
Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid status of the patient may necessitate adjustment in dosage.
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Pneumonia remains a major global health challenge, necessitating the development of effective therapeutic approaches. Recently, necroptosis, a regulated form of cell death, has garnered attention in the fields of pharmacology and immunology for its role in the pathogenesis of pneumonia. Characterized by cell death and inflammatory responses, necroptosis is a key mechanism contributing to tissue damage and immune dysregulation in various diseases, including pneumonia. This review comprehensively analyzes the role of necroptosis in pneumonia and explores potential pharmacological interventions targeting this cell death pathway. Moreover, we highlight the intricate interplay between necroptosis and immune responses in pneumonia, revealing a bidirectional relationship between necrotic cell death and inflammatory signaling. Importantly, we assess current therapeutic strategies modulating necroptosis, encompassing synthetic inhibitors, natural products, and other drugs targeting key components of the programmed necrosis pathway. The article also discusses challenges and future directions in targeting programmed necrosis for pneumonia treatment, proposing novel therapeutic strategies that combine antibiotics with necroptosis inhibitors. This review underscores the importance of understanding necroptosis in pneumonia and highlights the potential of pharmacological interventions to mitigate tissue damage and restore immune homeostasis in this devastating respiratory infection.
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The inventive pharmaceutical composition having thrombolytic anti-inflammatory and cytoprotective properties comprises active proteases attached to a gel or the mixture of gel and a water-soluble polymer. Said attachment is carried out with the aid of radiation, preferably gamma-radiation or accelerated electrons. Said composition also contains proteases which are stable at a temperature up to 70 °C, preferably at a temperature ranging from 30 to 40 °C, such as subtilisin, chymotripsin, papayotin or streptokinase. Polyethylene, dextrane or polyglicane gels are preferably used as a gel. The water-soluble polymer is embodied in the form of polyethylenglicol, polyvinyl alcohol, dextrane or polyglycan. The method for producing and using said composition is also disclosed. The inventive composition can be widely used for cardiology, nephrology, surgery rheumatology, gynecology and gastroenterology.
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FIELD: cosmetic industry. SUBSTANCE: invention relates to agents used for hair decolorization. Powder for hair decolorization has many particles containing peroxygenated salt, dust-removing agent in the amount less 10 wt. % of amount of decolorizing powder and powder-like polytetrafluoroethylene in the amount 1-5 wt.%. Powder increases solubility of decolorizing powder in hydrogen peroxide solution. EFFECT: improved indices of thixotropy and slipping, improved quality of decolorized hair. 7 cl, 7 tbl, 5 ex
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The Control group will be placed on a wait-list and offered services as soon as they complete the study's final 22-week follow-up measures. Control participants will not be assigned a Case Manager and will not receive any comparable services from our agency until they complete their 22-week measures.
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The REVERT-B trial is a multi-center, phase III, randomized 2x2 factorial study designed to test the efficacy of early maternal TDF vs standard duration and neonatal 3TC prophylaxis compared to matching placebo in preventing HBV MTCT. Eligible pregnant women with HBV in prenatal care (n=450) will be randomized 1:1:1:1 to one of four maternal and neonatal prophylaxis combinations (shown as A-D in the figure below). Women will initiate daily oral TDF early (2nd trimester) or at the standard time per WHO guidelines (3rd trimester) and will continue TDF until delivery. The current WHO standard of care in pregnant women with HBV (EAg+) in Cameroon is TDF prophylaxis from 28 weeks until delivery. Newborns will receive liquid 3TC or matching placebo for the first six months of life to provide coverage until the vaccine series is complete. All infants in the study will be offered the 4-dose HBV vaccine series starting at birth.
The 2x2 factorial design allows for two simultaneous studies where we first assess efficacy of early maternal prophylaxis (Aim 1) and secondarily assess efficacy of neonatal prophylaxis (Aim 2). The study endpoint for both aims is the MTCT rate (proportion of infants HBsAg+) at 6-9 months of age. Women and infants will be followed until 6-9 months after delivery and subaims will assess safety and adherence to maternal TDF and neonatal 3TC. Plasma testing will be used to measure medication adherence.
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Participants undergo echocardiograms with contrast done at baseline and at months 2, 4, 6, 12, 18, and 30. Electrocardiogram performed at baseline. Symptom questionnaire completed at baseline and at months 1, 2, 4, 6, 12, 18, and 30. Telephone follow-up by study staff at months 3 and 5.
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OBJECTIVE: Hyperuricaemia and gout are common metabolic disorders. However, the causal relationships between blood metabolites and serum urate levels, as well as gout, remain unclear. A systematic evaluation of the causal connections between blood metabolites, hyperuricemia, and gout could enhance early screening and prevention of hyperuricemia and gout in clinical settings, providing novel insights and approaches for clinical treatment.
METHODS: In this study, we employed a bidirectional two-sample Mendelian randomization analysis utilizing data from a genome-wide association study involving 7,286 participants, encompassing 486 blood metabolites. Serum urate and gout data were sourced from the Chronic Kidney Disease Genetics consortium, including 288,649 participants for serum urate and 9,819 African American and 753,994 European individuals for gout. Initially, LDSC methodology was applied to identify blood metabolites with a genetic relationship to serum urate and gout. Subsequently, inverse-variance weighting was employed as the primary analysis method, with a series of sensitivity and pleiotropy analyses conducted to assess the robustness of the results.
RESULTS: Following LDSC, 133 blood metabolites exhibited a potential genetic relationship with serum urate and gout. In the primary Mendelian randomization analysis using inverse-variance weighting, 19 blood metabolites were recognized as potentially influencing serum urate levels and gout. Subsequently, the IVW p-values of potential metabolites were corrected using the false discovery rate method. We find leucine (IVW P FDR = 0.00004), N-acetylornithine (IVW P FDR = 0.0295), N1-methyl-3-pyridone-4-carboxamide (IVW P FDR = 0.0295), and succinyl carnitine (IVW P FDR = 0.00004) were identified as significant risk factors for elevated serum urate levels. Additionally, 1-oleoylglycerol (IVW P FDR = 0.0007) may lead to a substantial increase in the risk of gout. Succinyl carnitine exhibited acceptable weak heterogeneity, and the results for other blood metabolites remained robust after sensitivity, heterogeneity, and pleiotropy testing. We conducted an enrichment analysis on potential blood metabolites, followed by a metabolic pathway analysis revealing four pathways associated with serum urate levels.
CONCLUSION: The identified causal relationships between these metabolites and serum urate and gout offer a novel perspective, providing new mechanistic insights into serum urate levels and gout.
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Patients receive mosunetuzumab IV over 2-4 hours on days 1, 8, and 15 of cycle 1 and then day 1 of each subsequent cycle. Treatment repeats every 28 days for 8 cycles in patients who achieve a CR or up to 17 cycles for patients with a PR or SD in the absence of disease progression or unacceptable toxicity. Patients also receive polatuzumab vedotin IV over 30-90 minutes on day 1 for 6 cycles and lenalidomide PO on days 1-21 for 8 cycles in patients who achieve CR or up to 17 cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT and blood sample collection throughout the study.
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Disclosed is a nucleic acid construct comprising a murine SOCS-3 promoter sequence having SEQ. ID. NO.: 1, or a non-murine homologue thereof, or an operative fragment or derivative. The construct can also contain, operatively linked to the SOCS-3 promoter, a gene encoding any preselected protein, and optionally contains a reporter gene to facilitate detection and/or selection of successfully transfected cells. Also disclosed are a transgenic vertebrate cell containing the nucleic acid construct and transgenic non-human vertebrates comprising such cells. The nucleic acid construct is useful in methods of treating a growth retardation or growth acceleration disorder in a human subject and in a method of treating an autoimmune disease, immune disease, or inflammatory condition in a human subject. A kit for genetically modifying a vertebrate cell includes a polynucleotide comprising the murine SOCS-3 promoter sequence is also disclosed.
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BACKGROUND: A previous term (≥37 weeks' gestation), full-dilatation cesarean delivery is associated with an increased risk for a subsequent spontaneous preterm birth. The mechanism is unknown. We hypothesized that the cesarean delivery scar characteristics and scar position relative to the internal cervical os may compromise cervical function, thereby leading to shortening of the cervical length and spontaneous preterm birth.
OBJECTIVE: This study aimed to determine the relationship of cesarean delivery scar characteristics and position, assessed by transvaginal ultrasound, in pregnant women with previous full-dilatation cesarean delivery with the risk of shortening cervical length and spontaneous preterm birth.
STUDY DESIGN: This was a single-center, prospective cohort study of singleton pregnant women (14 to 24 weeks' gestation) with a previous term full-dilatation cesarean delivery who attended a high-risk preterm birth surveillance clinic (2017-2021). Women underwent transvaginal ultrasound assessment of cervical length, cesarean delivery scar distance relative to the internal cervical os, and scar niche parameters using a reproducible transvaginal ultrasound technique. Spontaneous preterm birth prophylactic interventions (vaginal cervical cerclage or vaginal progesterone) were offered for short cervical length (≤25 mm) and to women with a history of spontaneous preterm birth or late miscarriage after full-dilatation cesarean delivery. The primary outcome was spontaneous preterm birth; secondary outcomes included short cervical length and a need for prophylactic interventions. A multivariable logistic regression analysis was used to develop multiparameter models that combined cesarean delivery scar parameters, cervical length, history of full-dilatation cesarean delivery, and maternal characteristics. The predictive performance of models was examined using the area under the receiver operating characteristics curve and the detection rate at various fixed false positive rates. The optimal cutoff for cesarean delivery scar distance to best predict a short cervical length and spontaneous preterm birth was analyzed.
RESULTS: Cesarean delivery scars were visualized in 90.5% (220/243) of the included women. The spontaneous preterm birth rate was 4.1% (10/243), and 12.8% (31/243) of women developed a short cervical length. A history- (n=4) or ultrasound-indicated (n=19) cervical cerclage was performed in 23 of 243 (9.5%) women; among those, 2 (8.7%) spontaneously delivered prematurely. A multiparameter model based on absolute scar distance from the internal os best predicted spontaneous preterm birth (area under the receiver operating characteristics curve, 0.73; 95% confidence interval, 0.57-0.89; detection rate of 60% for a fixed 25% false positive rate). Models based on the relative anatomic position of the cesarean delivery scar to the internal os and the cesarean delivery scar position with niche parameters (length, depth, and width) best predicted the development of a short cervical length (area under the receiver operating characteristics curve, 0.79 [95% confidence interval, 0.71-0.87]; and 0.81 [95% confidence interval, 0.73-0.89], respectively; detection rate of 73% at a fixed 25% false positive rate). Spontaneous preterm birth was significantly more likely when the cesarean delivery scar was <5.0 mm above or below the internal os (adjusted odds ratio, 6.87; 95% confidence interval, 1.34-58; P =.035).
CONCLUSION: In pregnancies following a full-dilatation cesarean delivery, cesarean delivery scar characteristics and distance from the internal os identified women who were at risk for spontaneous preterm birth and developing short cervical length. Overall, the spontaneous preterm birth rate was low, but it was significantly increased among women with a scar located <5.0 mm above or below the internal cervical os. Shortening of cervical length was strongly associated with a low scar position. Our novel findings indicate that a low cesarean delivery scar can compromise the functional integrity of the internal cervical os, leading to cervical shortening and/or spontaneous preterm birth. Assessment of the cesarean delivery scar characteristics and position seem to have use in preterm birth clinical surveillance among women with a previous, full-dilatation cesarean delivery and could better identify women who would benefit from prophylactic interventions.
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Elevated Liver Enzymes
CAMRESE LO is contraindicated in females with acute viral hepatitis or severe (decompensated) cirrhosis of the liver [see Contraindications (4)]. Acute liver test abnormalities may necessitate the discontinuation of CAMRESE LO until the liver tests return to normal and CAMRESE LO causation has been excluded. Discontinue CAMRESE LO if jaundice develops.
Liver Tumors
CAMRESE LO is contraindicated in females with benign or malignant liver tumors [see Contraindications (4)]. COCs increase the risk of hepatic adenomas. An estimate of the attributable risk is 3.3 cases/100,000 COC users. Rupture of hepatic adenomas may cause death from abdominal hemorrhage.
Studies have shown an increased risk of developing hepatocellular carcinoma in long-term (> 8 years) COC users. The attributable risk of liver cancers in COC users is less than one case per million users.
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Testosterone esters for use in pharmaceutical hormone preparations (see Group VI) may be produced by conventional methods. For example, testosterone undecylenate is prepared by reacting testosterone with undecylenyl chloride in anhydrous benzene in the presence of anhydrous pyridine. Other esters specified are the valerate and propionate.ALSO:A mixture of testosterone undecylenate, testosterone valerate and testosterone propionate is used in hormone preparations such as solutions (especially oil solutions) for parenteral administration, suspensions, emulsions, implantates, tablets, dragees, salves and creams. Specified carrier materials include vegetable oils, benzyl alcohol, polyethylene glycols, gelatine, lactose, starch, magnesium stearate, talc, petroleum jelly and cholesterol. Additional additives include preserving, stabilizing, wetting or emulsifying agents, buffer substances, local anaesthetics and substances having an effect on the blood vessels. Examples are given of a preparation in sesame oil, a preparation in crystal form and of a tablet.
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PROBLEM TO BE SOLVED: To obtain an expected medical effect by adjusting the dissolved oxygen content and oxidation-reduction potential of the electrolytic water to specified values or less respectively. SOLUTION: The dissolved oxygen content and oxidation-reduction potential of this electrolytic water are adjusted to <=3.0ppm, preferably <=2.0ppm and more desirably <=1.0ppm and to <=-300mV, preferably <=-500mV and more desirably <=-700mV, respectively. As the electrolytic water production equipment, e.g. an equipment in which an electrolytic tank 1 is divided into an electrolytic room 5 and another electrolytic room 6 with a diaphragm 4 placed in the central part of the electrolytic tank 1, is used. Also, a voltage is applied to between two electrode plates 2 and 3 so that the current passing through an electrolyte between the electrode plates 2 and 3 is constant to perform electrolysis. As each of the electrode plates 2 and 3 placed in the electrolytic tank 1, a platinum plated titanium plate is used. Thus, since the dissolved oxygen content in the electrolytic water is remarkably low, drinking water with which the amount of active oxygen that is a by-product of a metabolism utilizing an enzyme can be reduced and any oxidation of genes and cells can be inhibited from occurring, is produced.
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The study will recruit 20 young healthy Asian men of Chinese descent. Subjects will visit our Clinical Nutrition Research Centre (CNRC) on 5 occasions: once for consenting, screening and familiarization with the exercise and testing equipment (screening), and four additional times, interspaced by a minimum of 3 days, to undergo a total of four study conditions. The four study trials combine SIT or rest and low or high GI diet in a 2 x 2 design, and will be assigned in randomized order: (RL) Rest and low GI, (SL) SIT and low GI, (RH) Rest and high GI, and (SH) SIT and high GI. The test conditions will have comparable foods with RL and SL diets comprising local foods of low glycaemic index and RH and SH diets comprising local foods of high glycaemic index. Randomization of study trials will be carried out using an online randomizer (www.randomizer.org/). In the SL and SH trials, subjects will perform a SIT bout consisting of alternating periods of low-resistance cycling (4 ½ minutes) and maximal effort all out cycling (30 sec Wingate test) for a total of 30 min (i.e. a total of 6 Wingate tests)\*, whereas in the RL and RH trials, subjects will rest for the equivalent period of time (i.e. 30 min). For screening, potential subjects will come in the morning after an overnight fast. After obtaining informed consent, a series of screening tests will be conducted, including questionnaires (general health, physical activity and eating behaviour), anthropometry (height, weight, waist and hip circumference), blood pressure, resting heart rate, fasting blood glucose, HbA1c and body composition by air displacement plethysmography (BodPod, Cosmed, Rome, Italy). Following enrolment, subjects will undergo assessment of resting metabolic rate (RMR) for 30 minutes using a ventilated hood system (Quark CPET, Cosmed, Rome, Italy). RMR will be multiplied by a factor of 1.5 to approximate total energy requirement for weight maintenance. This will allow for tailoring the caloric content of the test meals to each subject's energy requirements. Thereafter, subjects will eat a small standardized breakfast and they will perform a 30-min SIT session to get familiarized with the exercise and the equipment. The total time required for screening will be around 2 hours. After the screening, subjects will be provided with a food diary to record all food intake on Day 1 and an activity diary to record all activities on Days 1 and 2 of the actual study trials (see below). Although only sedentary subjects will be recruited (=60 min of moderate-intensity exercise weekly), they will also be instructed to refrain from any vigorous activities during the three days before each study trials and throughout its duration. On Visits 2 to 5 (four experimental trials, in random order): Each of the four study visits will last for approximately 12 hours (spanning over 3 days), during which the following will take place: On Day 1, subjects will come to the Lab at around 4:00 pm to have the continuous glucose monitoring system (CGMS) inserted. CGMS will be used to measure 24 hour blood glucose concentrations. The sensor records interstitial blood glucose concentrations every five minutes. This will involve the insertion of a small sensor under the skin in the abdomen, which will be carried out by using a device that produces minimal pain and discomfort. After insertion, the stabilizing and calibration procedures will take 2 hours after which the subjects will go home with a standardized dinner to eat at around 7:00pm. Subjects will have to refrain from eating after 10:30pm and return to the CNRC the following morning (Day 2).On Day 2, subjects will report to the lab at 8:15 am following an overnight fast for the first of the four study conditions. Upon arrival, an indwelling catheter will be inserted into the antecubital fossa or forearm vein of one arm and will be kept patent. Blood samples will be obtained after the insertion of the catheter at 8:30 am (time = -30 min). Between 8:30 am and 9:00 am, subjects will either rest for 30 minutes or perform the SIT bout which will start with 4 ½ minutes of low-resistance cycling followed by 30 seconds of maximum effort, repeated for a total of 6 times\*. During the SIT, subjects' ratings of perceived exertion (RPE) will be measured periodically using the Borg scale. At 9:00 am, blood samples will be collected (time = 0 min), after which breakfast (low or high GI) will be provided. After finishing breakfast, at 9:15 am, blood samples will be collected every 10 minutes for the first half hour and every 30 minutes for the remaining 3 hours at 15, 25, 35, 45, 75, 105, 135, 165, and 195 minutes. Before lunch is served at 12:45pm (time = 225 min), blood will be collected and again after lunch at 1:00 pm (time = 240 min), followed by blood collection every 10 minutes for the first half hour and every 30 minutes for the remaining 3 hours at 250, 260, 270, 300, 330, 360, 390, 420 and 450 minutes. After the last blood sample is collected at 4:30 pm, the catheter will be removed and the subjects will be discharged from the Lab. Subjects will be provided with the last test meal of the day (dinner) to eat at home at around 7:00pm. Throughout the day and at specific times, subjects will complete computerized visual analogue scales (VAS) on hunger and fullness. Blood samples will be used to measure fasting and postprandial concentrations of glucose and major glucoregulatory hormones like insulin and glucagon. C-peptide concentrations will be used to provide estimates of insulin secretion with mathematical modelling. Blood lactate will be determined before and after exercise to verify maximal exercise effort. On Day 3, subjects will come to the Lab at 8:30 am for final calibration and removal of the CGMS sensor. Subjects will come to the Lab for visits 3, 4, and 5 to perform the other 3 experimental trials, with at least 3 days wash-out in-between visits.
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Belzutifan is an inhibitor of hypoxia-inducible factor 2 alpha (HIF-2α). HIF-2α is a transcription factor that plays a role in oxygen sensing by regulating genes that promote adaptation to hypoxia. Under normal oxygen levels, HIF-2α is targeted for ubiquitin-proteasomal degradation by VHL protein. Lack of functional VHL protein results in stabilization and accumulation of HIF-2α. Upon stabilization, HIF-2α translocates into the nucleus and interacts with hypoxia-inducible factor 1 beta (HIF-1β) to form a transcriptional complex that induces expression of downstream genes, including genes associated with cellular proliferation, angiogenesis, and tumor growth. Belzutifan binds to HIF-2α, and in conditions of hypoxia or impairment of VHL protein function, belzutifan blocks the HIF-2α-HIF-1β interaction, leading to reduced transcription and expression of HIF-2α target genes. In vivo, belzutifan demonstrated anti-tumor activity in mouse xenograft models of renal cell carcinoma.
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<P>PROBLEM TO BE SOLVED: To provide a composition and a method for imaging β-cells in vivo, and a composition and a method for improving diagnosis and treatment of pancreas-associated diseases based on finding the delivery of a pharmaceutical agent having therapeutic value specific to pancreatic β-cells. <P>SOLUTION: The composition for imaging the β-cells includes a chelating agent-antidiabetic agent conjugate and, if needed, a metal to be chelated. The composition for imaging the pancreas including the antidiabetic agent, the chelating agent and a metal ion to be chelated are disclosed. The method for treating the pancreas is also disclosed. The method includes a process for administering the composition including the antidiabetic agent, the chelating agent and the metal ion to be chelated to subjects requiring the treatment of pancreatic diseases. In the composition, the metal ion is a β-ray emitter. <P>COPYRIGHT: (C)2011,JPO&INPIT
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PURPOSE: The percentage of retroperitoneal sarcomas (RPS) among all soft tissue sarcomas ranges from 10 to 15%. Surgery remains the gold standard for RPS. In this study, we analyzed the impact of surgical treatment for primary RPS on recurrence and overall mortality at a Chinese institution and identified and evaluated prognostic variables.
METHODS: Data from patients with RPS who underwent surgical treatment were retrospectively analyzed. The patients were treated at a single center from January 2000 to June 2018. Retrospectively collected demographic, clinicopathological, and surgical factors were examined. Overall survival (OS) and disease-free survival (DSF) were used as the primary endpoints. Predicted 5-year survival rates, encompassing both DFS and OS, were derived from the Sarculator prognostic nomogram.
RESULTS: A total of 110 patients met the inclusion criteria. The median follow-up time after surgery for patients with primary RPS was 5.3 years. During this period, 59 patients died. The 5-year OS and DFS estimates were 63.5% and 35.3%, respectively. In a multivariate analysis, poor OS following surgical treatment of primary RPS was independently correlated with FNCLCC grade (p < 0.001) and surgical margin status (p = 0.016). FNCLCC grade (p = 0.001) and surgical margin status (p = 0.002) were also independently associated with poor DFS. The C-indices for 5-year OS and DFS survival utilizing the Sarculator prognostic nomogram were 0.71 and 0.73 respectively.
CONCLUSION: The overall mortality rate of patients with RPS was considered acceptable. OS and DFS prognostic markers were established for primary RPS. Tumor grade and intraregional margins are other factors that affect survival and recurrence.
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Pathology grading of prostate biopsy follows the rule that the highest International Society of Urological Pathology grade group (GG) is the GG assigned. This rule was developed in the systematic biopsy (SBx) era and makes sense when samples are from very different areas of the prostate. This rule has been kept for multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy (MRI-TBx), for which multiple samples-targeted and systematic-are taken from small areas. In particular, if the results for SBx and MRI-TBx are discordant, the patient is assigned the higher GG. However, the most appropriate grading when MRI-TBx and SBx grades are discordant has never been investigated empirically. A cohort of patients who have undergone SBx and MRI-TBx with long oncological follow-up does not yet exist. To estimate the risk of recurrence for every combination of biopsy and pathological grades, we used the GG on radical prostatectomy (RP) as a surrogate for GG on MRI-TBx GG surrogate. We analyzed data for 12 468 men who underwent SBx and RP at a tertiary referral center and assessed 5-yr biochemical recurrence-free survival (bRFS) for each pairwise combination of biopsy and surgical GG results. We found that for cases with discordant SBx and RP grades, the risk of recurrence was intermediate, irrespective of whether the highest grade was at RP or SBx. For instance, the 5-yr bRFS rate was 57% for men with GG 3 on RP and 60% for men with GG 3 on SBx, but 63% for men with RP GG 3 and SBx GG 2, and 79% for men with RP GG 2 and SBx GG 3. Translating these findings to MRI-TBx casts doubt on current grading practice: when GGs are discordant between SBx and MRI-TBx, the risk of biochemical recurrence risk is not driven by the highest grade but by an intermediate between the two grades. Our findings should motivate studies assessing long-term outcomes for patients undergoing both MRI-TBx and SBx with a view to empirically evaluating current grading practices. PATIENT SUMMARY: Patients with prostate cancer may undergo two biopsy types: (1) systematic biopsy, for which sampling follows a systematic template; and (2) targeted biopsy, for which samples are taken from lesions detected on scans. There may be a difference in prostate cancer grade identified by the two approaches. In such cases, the risk of cancer recurrence seems to be predicted by an intermediate grade between the lower and higher grades.
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Carcinogenesis
Long-term studies to evaluate the carcinogenic potential of hydromorphone hydrochloride were completed in both Han-Wistar rats and Crl:CD1®(ICR) mice. Hydromorphone HCl was administered to Han-Wistar rats (2, 5, and 15 mg/kg/day for males, and 8, 25 and 75 mg/kg/day for females) for 2 years by oral gavage. In female rats, incidences of hibernoma (tumor of brown fat) were increased at 10.5 times the maximum recommended daily exposure based on AUC at the mid dose (2 tumor, 25 mg/kg/day) and 53.7 times the maximum recommended human daily exposure based on AUC at the maximum dose (4 tumors, 75 mg/kg/day). The clinical relevance of this finding to humans has not been established. There was no evidence of carcinogenicity in male rats. The systemic drug exposure (AUC, ng•h/mL) at the 15 mg/kg/day in male rats was 7.6 times greater than the human exposure at a single dose of 32 mg/day of hydromorphone hydrochloride extended-release tablets. There was no evidence of carcinogenic potential in Crl:CD1®(ICR) mice administered hydromorphone HCl at doses up to 15 mg/kg/day for 2 years by oral gavage. The systemic drug exposure (AUC, ng•h/mL) at the 15 mg/kg/day in mice was 1.1 (in males) and 1.2 (in females) times greater than the human exposure at a single dose of 32 mg/day of hydromorphone hydrochloride extended-release tablets.
Mutagenesis
Hydromorphone was not mutagenic in the in vitro bacterial reverse mutation assay (Ames assay). Hydromorphone was not clastogenic in either the in vitro human lymphocyte chromosome aberration assay or the in vivo mouse micronucleus assay.
Impairment of Fertility
Reduced implantation sites and viable fetuses were noted at 2.1 times the human daily dose of 32 mg/day in a study in which female rats were treated orally with 1.75, 3.5, or 7 mg/kg/day hydromorphone hydrochloride (0.7, 1.4, or 2.8 times a human daily dose of 24 mg/day (HDD) based on body surface area) beginning 14 days prior to mating through Gestation Day 7 and male rats were treated with the same hydromorphone hydrochloride doses beginning 28 days prior to and throughout mating.
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Human Experience
In premarketing experience with oral risperidone, there were eight reports of acute risperidone overdosage with estimated doses ranging from 20 to 300 mg and no fatalities. In general, reported signs and symptoms were those resulting from an exaggeration of the drug's known pharmacological effects, i.e., drowsiness and sedation, tachycardia and hypotension, and EPS. In one case, hyponatremia, hypokalemia, prolonged QT, and widened QRS were observed after a patient took an estimated 240 mg of oral risperidone. In another case, a patient had a seizure after taking an estimated 36 mg of oral risperidone.
Postmarketing experience with oral risperidone included reports of acute overdose with estimated doses up to 360 mg. In general, the most frequently reported signs and symptoms were those resulting from an exaggeration of the drug's known pharmacological effects, i.e., drowsiness, sedation, tachycardia, hypotension, and EPS. Other postmarketing adverse reactions related to oral risperidone overdose included prolonged QT interval and convulsions. Torsade de pointes was reported in association with combined overdose of oral risperidone and paroxetine.
Management of Overdosage
In case of acute overdosage, establish and maintain an airway and ensure adequate oxygenation and ventilation. Cardiovascular monitoring should commence immediately and include continuous electrocardiographic monitoring to detect possible arrhythmias. If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine carry a theoretical hazard of QT prolonging effects that might be additive to those of risperidone. Similarly, it is reasonable to expect that the alpha-blocking properties of bretylium might be additive to those of risperidone, resulting in problematic hypotension.
There is no specific antidote to risperidone. Therefore, appropriate supportive measures should be implemented. The possibility of multiple drug involvement should be considered. Hypotension and circulatory collapse should be treated with appropriate measures, such as intravenous fluids and/or sympathomimetic agents (epinephrine and dopamine should not be used, since beta stimulation may worsen hypotension in the setting of risperidone-induced alpha blockade). In cases of severe EPS, anticholinergic medication should be administered. Close medical supervision and monitoring should continue until the patient recovers.
Consider contacting the Poison Help line (1-800-222-1222) or medical toxicologist for additional overdosage management recommendations.
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Background: Complications associated with the use of autologous and homologous costal cartilage for nasal tip stabilizing grafts in septorhinoplasty are not well understood. Objective: The authors review current literature to evaluate complications associated with autologous and irradiated homologous costal cartilage (IHCC) used for septal extension and columellar strut grafts in rhinoplasty. Method: A comprehensive literature search was conducted in PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov. Articles that used autologous or IHCC for either septal extension or columellar strut grafts in patients undergoing septorhinoplasty were included. The primary outcomes analyzed were postoperative complications. Results: A total of 14 studies representing 1358 patients were included. The pooled complication rate was 4.7%. IHCC grafts were associated with a higher incidence of complications (n = 21, 5.0% vs. n = 44, 4.6%, p = 0.01). Resorption was the most common complication in the IHCC group and occurred significantly more frequently than in the autologous costal cartilage (ACC) group (n = 10, 2.4% vs. n = 5, 0.49%, p = 0.002). Deviation/warping was the most common complication in the ACC group (n = 16, 1.7%). Conclusion: Autologous and irradiated homologous costal rhinoplasties remain safe procedures. The increased incidence of resorption associated with IHCC grafts should be considered during preoperative planning.
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Glioblastoma (GBM) is an extremely aggressive tumor associated with a poor prognosis that impacts the central nervous system. Increasing evidence suggests an inherent association between glucose metabolism dysregulation and the aggression of GBM. Polo-like kinase 4 (PLK4), a highly conserved serine/threonine protein kinase, was found to relate to glioma progression and unfavorable prognosis. As revealed by the integration of proteomics and phosphoproteomics, PLK4 was found to be involved in governing metabolic processes and the PI3K/AKT/mTOR pathway. For the first time, this study supports evidence demonstrating that PLK4 activated PI3K/AKT/mTOR signaling through direct binding to AKT1 and subsequent phosphorylating AKT1 at S124, T308, and S473 to promote tumorigenesis and glucose metabolism in glioma. In addition, PLK4-mediated phosphorylation of AKT1 S124 significantly augmented the phosphorylation of AKT1 S473. Therefore, PLK4 exerted an influence on glucose metabolism by stimulating PI3K/AKT/mTOR signaling. Additionally, the expression of PLK4 protein exhibited a positive correlation with AKT1 phosphorylation in glioma patient tissues. These findings highlight the pivotal role of PLK4-mediated phosphorylation of AKT1 in glioma tumorigenesis and dysregulation of glucose metabolism.
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Metastasis accounts for almost 90% of breast cancer-related fatalities, making it frequent malignancy and the main reason of tumor mortality globally among women. LSD1 is a histone demethylase, which plays an important role in breast cancer. In order to explore the effect of LSD1 on invasion and migration of breast cancer, we treated breast cancer cells with MCF7 and T47D exosomes knocked down by LSD1, and the invasion and migration of breast cancer cells were significantly enhanced. This phenomenon indicates that LSD1 can inhibit the invasion and migration of breast cancer cells. miR-1290 expression was downregulated in LSD1 knockdown MCF7 exosomes. By analyzing the database of miR-1290 target gene NAT1, we verified that miR-1290 could regulate the expression of NAT1. These data provide fresh insights into the biology of breast cancer therapy by demonstrating how the epigenetic factor LSD1 stimulates the breast cancer cells' invasion and migration via controlling exosomal miRNA.
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The human brain has been implicated in the pathogenesis of several complex diseases. Taking advantage of single-cell techniques, genome-wide association studies (GWAS) have taken it a step further and revealed brain cell-type-specific functions for disease loci. However, genetic causal associations inferred by Mendelian randomization (MR) studies usually include all instrumental variables from GWAS, which hampers the understanding of cell-specific causality. Here, we developed an analytical framework, Cell-Stratified MR (csMR), to investigate cell-stratified causality through colocalizing GWAS signals with single-cell eQTL from different brain cells. By applying to obesity-related traits, our results demonstrate the cell-type-specific effects of GWAS variants on gene expression, and indicate the benefits of csMR to identify cell-type-specific causal effect that is often hidden from bulk analyses. We also found csMR valuable to reveal distinct causal pathways between different obesity indicators. These findings suggest the value of our approach to prioritize target cells for extending genetic causation studies.
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Participants will receive a equimolar amount of sodium chloride (S9888, MilliporeSigma) mixed with water. The amount of water, lemon juice, and crystal light will be matched to that of the sodium lactate condition.
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The invention provides application of theanine in preparation of a histone deacetylase inhibitor and relates to the technical field of medical treatment. The theanine is a characteristic amino acid of tea, can inhibit cancer cell growth and invasion of a pancreatic cancer, a cervical cancer, a stomach cancer, a breast cancer and other cancers and can significantly inhibit the growth of tumors in a body, and the inhibition effect of the theanine exceeds those of an anti-cancer drug cyclophosphamide and the like. An action mechanism relates to receptors closely relevant with down regulation and inhabiting the growth, invasion and metastasis of the tumors, signal transduction for protein and kinase level regulation and control and nuclear factor and DNA combination, and meanwhile a cancer suppressor protein, cell cycle arrestin and other factors are up-regulated. The theanine can directly inhibit the activity of histone deacetylase and histone transmethylase EZH2 and combination of an inflammatory factor NF-kappa B and DNA. In addition, the theanine can cooperate with 6-fluoride-4-hydroxyl coumarin (X) to manifold improve the inhibition to tumor cell growth and invasion, and the activity of the theanine is greater than those of the cyclophosphamide and the like. The invention provides the theanine and novel application of the theanine in prevention and treatment of tumors, inflammations, heart and cerebral vessels, immunodeficiency and other diseases in coordination with the X.
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This is a non-randomized, non-blinded, prospective, single-arm, single-center pilot study, enrolling up to 15 pediatric subjects in two cohorts (5 subjects age 6-12 and 10 subjects age 13-17) with diabetes mellitus for up to 180 days. Study will evaluate the system at home with comparison to SMBG with clinic check visits and downloading of stored data every 30 days. Subjects will have one Sensor inserted subcutaneous by trained Investigators. The System will be set to provide real-time glucose information, including alarms and alerts in the home settings. The system is for adjunctive use. All diabetes care decisions will be based on SMBG values rather than System CGM results.
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The invention provides siRNA for specifically inhibiting chicken CTGF gene expression and application thereof. The sequences of the sense strand and the antisense strand of the siRNA are respectively shown as SEQ ID NO.1 and SEQ ID NO. 2. The CTGF target sequence of the siRNA interference is shown as SEQ ID NO. 3. The antisense strand of the siRNA molecule can be specifically combined with mRNA for inhibiting chicken CTGF gene to degrade the mRNA, thereby interfering the posttranscriptional translation process and promoting chicken preadipocyte differentiation. The siRNA provided by the invention has the advantages of high interference efficiency and good specificity on transcription level, high sensitivity, simple and convenient operation, short experimental period and low price compared with the gene knockout technology, and provides a direct and effective experimental tool for researching the functions and regulation mechanisms of the avian CTGF genes.
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Cannabis use and availability continue to rise significantly in the US. It is critical to expand our knowledge of the negative and positive effects of cannabis to "catch up" to the current reality of widespread and growing use. Cannabis and tetrahydrocannabinol (THC), its primary psychoactive chemical, have widespread effects on neural glutamate homeostasis, and specifically metabotropic glutamate receptor 5 (mGluR5). mGluR5 regulates transmission of glutamate and plays a critical role in neural plasticity (i.e., long-term potentiation; LTP), memory, learning, mood, and addiction. Specifically, it is thought that mGluR5 activation by glutamate initiates production of endocannabinoids (i.e., 2-AG) that bind retrograde to presynaptic cannabinoid receptor 1. This pathway inhibits further glutamate release and modulates synaptic plasticity diffusely in the brain. However, cannabis use disrupts this normal mechanism of glutamate homeostasis. While the relationship between cannabis use and glutamate regulation has been explored in preclinical models, it has not been well-characterized in humans, and particularly in people with cannabis use disorder (CUD).
The goal is to test the overall hypothesis that mGluR5 availability is higher in people with CUD compared with HC. This study will advance our understanding of cannabis effects on the neural glutamate system in humans and may lead to the development of novel therapeutics and biomarkers to treat people with CUD. Aim 1 will determine differences in mGluR5 availability between people with CUD and HC in the fronto-limbic brain circuit. Aim 2 examines the associations between mGluR5 availability, CUD severity, neural oscillations, and cognitive function in CUD subjects. Aim 3 will determine how prolonged abstinence from chronic cannabis use affects mGluR5 availability, neural oscillations, and cognitive function in CUD subjects.
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(see also PRECAUTIONS, Drug-Drug Interactions)
Multiple metabolic pathways and renal excretion are involved in the elimination of galantamine so no single pathway appears predominant. Based on in vitro studies, CYP2D6 and CYP3A4 were the major enzymes involved in the metabolism of galantamine. CYP2D6 was involved in the formation of O-desmethyl-galantamine, whereas CYP3A4 mediated the formation of galantamine-N-oxide. Galantamine is also glucuronidated and excreted unchanged in urine.
(A) Effect of Other Drugs on the Metabolism of Galantamine Hydrobromide:
Drugs that are potent inhibitors for CYP2D6 or CYP3A4 may increase the AUC of galantamine. Multiple dose pharmacokinetic studies demonstrated that the AUC of galantamine increased 30% and 40%, respectively, during coadministration of ketoconazole and paroxetine. As co-administered with erythromycin, another CYP3A4 inhibitor, the galantamine AUC increased only 10%. Population PK analysis with a database of 852 patients with Alzheimer’s disease showed that the clearance of galantamine was decreased about 25-33% by concurrent administration of amitriptyline (n = 17), fluoxetine (n = 48), fluvoxamine (n = 14), and quinidine (n = 7), known inhibitors of CYP2D6.
Concurrent administration of H2-antagonists demonstrated that ranitidine did not affect the pharmacokinetics of galantamine, and cimetidine increased the galantamine AUC by approximately 16%.
A multiple dose pharmacokinetic study with concurrent administration of memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, demonstrated that co-administration of memantine in a dose of 10 mg BID did not affect the pharmacokinetic profile of galantamine (16 mg daily) at steady state.
(B) Effect of Galantamine Hydrobromide on the Metabolism of Other Drugs:
In vitro studies show that galantamine did not inhibit the metabolic pathways catalyzed by CYP1A2, CYP2A6, CYP3A4, CYP4A, CYP2C, CYP2D6 and CYP2E1. This indicated that the inhibitory potential of galantamine towards the major forms of cytochrome P450 is very low. Multiple doses of galantamine (24 mg/day) had no effect on the pharmacokinetics of digoxin and warfarin (R- and S- forms). Galantamine had no effect on the increased prothrombin time induced by warfarin.
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Currently, there is little information about which is the safest modality in the first session of intermittent hemodialysis. Other than dialysis-associated imbalance syndrome, there is no evidence exploring the neurocognitive effects of the first hemodialysis session. Cognitive impairment is defined as a new deficit in two or more areas of cognitive function and its progression is associated with impaired kidney function. Most of the dysfunctions reported are in the domains of orientation, attention and executive functions. Therefore, the recognition of cognitive impairment can be done with tools such as the Minimental State Examination (MMSE) and the Montreal Cognitive Assessment (MOCA) test. Brain magnetic resonance imaging (MRI) can identify brain lesions such as 'silent' infarcts, microbleeds and white matter abnormalities in patients with CKD with and without RRT. Diffusion-weighted MRI before and after HD has shown brain edema in rats with dialysis-associated imbalance syndrome. In fact, there is evidence from brain MRI that before first HD session patients have interstitial cerebral edema, which worsens after the first HD treatment.
Because there is no clear evidence to support the choice of the modality in the first session and the prescription is still based on personal experiences and shared views. Therefore, we conducted a pilot study to determine the safest hemodialysis modality with the lowest risks and neurocognitive effects for patients with CKD and first HD treatment.
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The broad objective is to establish a Center of Excellence for Research on Obesity at The Children's Hospital of Philadelphia (CHOP) that will create a statewide, collaborative research network to develop and test effective treatments for reducing adolescent obesity and related medical co-morbidities in underserved populations. Collaborating institutions include Lincoln University (LU), Geisinger Health System (GHS), and the University of Pennsylvania (UPenn). Given the locations of these institutions, we will focus on urban African Americans and Latinos and rural Caucasian adolescents. The novelty of this program will be the use of a family-based, lifestyle modification program within the pediatric primary care setting with interdisciplinary teams trained to treat obese adolescents. Specific aims are to: a) design, implement, and evaluate improved treatments for obese teenagers, b) conduct focus groups and treatment development projects to better understand the needs of these populations and c) train, minority students and faculty to become healthcare research professionals. The primary research project will be a randomized clinical trial occurring at two sites: CHOP and GHS. In a four-year study, 156 adolescents (ages 12-16) will be randomized to either a one-year, 23 session, multi-family, group based Lifestyle Modification Program known as the Group Condition, or to a one-year, six-session Self-Guided Condition. Both Group and Self-Guided will be tested as possible treatment protocols for primary care pediatric practice.
The primary aim is to compare the effectiveness of these two treatments in reducing body mass index (BMI) at 12 months. Secondary aims will compare impact of the treatments on reduction of risk factors related to cardiovascular disease and diabetes, including lipids, glucose and insulin, waist circumference, blood pressure, and measures of appetite. Further, the effectiveness of these two treatments in reducing BMI at 15 and 18 months will also be analyzed. Training aims will be met through collaboration with Lincoln University to set up undergraduate summer internships, graduate assistantships, and faculty development. Other methods for achieving the objectives of the Center include: a) establishing a multidisciplinary advisory board consisting of parents, providers, and researchers; b) providing clinical training in obesity treatment for doctors, nurses, dieticians, and behavioral interventionists at our collaborating institutions (CHOP and GHS); c) making all protocols and materials culturally sensitive to the populations they serve; and d) carrying out treatment development activities to tailor the manuals for Latino youth and their families.
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Each tablet, for oral administration, contains oxycodone hydrochloride and acetaminophen in the following strengths:
Oxycodone Hydrochloride USP ..........................................................................5 mg* Acetaminophen USP ........................................................................................325 mg *5 mg oxycodone HCl is equivalent to 4.4815 mg of oxycodone. Oxycodone Hydrochloride USP .......................................................................7.5 mg* Acetaminophen USP ........................................................................................325 mg *7.5 mg oxycodone HCl is equivalent to 6.7228 mg of oxycodone. Oxycodone Hydrochloride USP .......................................................................7.5 mg* Acetaminophen USP ........................................................................................500 mg *7.5 mg oxycodone HCl is equivalent to 6.7228 mg of oxycodone. Oxycodone Hydrochloride USP .........................................................................10 mg* Acetaminophen USP .........................................................................................325 mg *10 mg oxycodone HCl is equivalent to 8.9637 mg of oxycodone.
All strengths of oxycodone and acetaminophen tablets USP also contain the following inactive ingredients: crospovidone, microcrystalline cellulose, povidone, pregelatinized starch, silicon dioxide and stearic acid.
Oxycodone, 4,5α-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one hydrochloride, is a semisynthetic opioid analgesic which occurs as a white, odorless, crystalline powder having a saline, bitter taste. It is derived from the opium alkaloid thebaine. Oxycodone hydrochloride may be represented by the following structural formula:
Acetaminophen, 4'-hydroxyacetanilide, is a non-opiate, non-salicylate analgesic and antipyretic which occurs as a white, odorless, crystalline powder, possessing a slightly bitter taste. It may be represented by the following structural formula:
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The present invention relates to methods for improving the overall survival of a patient suffering from a malignant disease or a disease involving physiological and pathological angiogenesis by treatment with an angiogenesis inhibitor, such as bevacizumab, by determining the presence of one or more variant alleles of the vascular endothelial growth factor receptor 1 (VEGFR-1) gene. The present invention further provides methods for improving the progression-free survival of a patient suffering from a malignant disease or a disease involving physiological and pathological angiogenesis by treatment with an angiogenesis inhibitor, such as bevacizumab, by determining the presence of one or more variant alleles of the VEGFR-1 gene. The present invention also provides for methods for assessing the responsiveness of a patient to an angiogenesis inhibitor by determining the presence of one or more variant alleles of the VEGFR-1 gene. The present invention relates to methods for improving the overall survival of a patient suffering from a malignant disease or a disease involving physiological and pathological angiogenesis by treatment with an angiogenesis inhibitor, such as bevacizumab, by determining the presence of one or more variant alleles of the vascular endothelial growth factor receptor 1 (VEGFR-1) gene. The present invention further provides methods for improving the progression-free survival of a patient suffering from a malignant disease or a disease involving physiological and pathological angiogenesis by treatment with an angiogenesis inhibitor, such as bevacizumab, by determining the presence of one or more variant alleles of the VEGFR-1 gene. The present invention also provides for methods for assessing the responsiveness of a patient to an angiogenesis inhibitor by determining the presence of one or more variant alleles of the VEGFR-1 gene. The invention relates to a method for determining the clamping force on a mechanical joint connection connecting at least two components by coupling sound waves into the joint connection. The invention is characterized by the combination of the following method steps: exciting the mechanical joint connection in order to generate oscillation, capturing the oscillations made by the joint connection due to the excitement, and analyzing the oscillations of the joint connection on the basis of reference oscillation patterns stored in a reference dataset, a known clamping force prevailing in the joint connection to be tested being associated with each pattern.
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Fracture risk assessment in patients with chronic kidney disease (CKD) has been included in the CKD-MBD ("Chronic Kidney Disease-Mineral and Bone Disorders") complex in international and national nephrology guidelines, suggesting for the first time the assessment of bone mineral density (BMD) if the results can influence therapeutic decision-making. However, there is very little information on actual clinical practice in this population. The main objective of the ERCOS (ERC-Osteoporosis) study is to describe the profile of patients with CKD G3-5D with osteoporosis (OP) and/or fragility fractures treated in specialized nephrology, rheumatology and internal medicine clinics in Spain. Fifteen centers participated and 162 patients (mostly women [71.2%] postmenopausal [98.3%]) with a median age of 77 years were included. Mean estimated glomerular filtration rate (eGFR) was 36 mL/min/1.73 m2 and 38% of the included patients were on dialysis. We highlight the high frequency of prevalent fragility fractures [37.7%), mainly vertebral (52.5%) and hip (24.6%)], the disproportionate history of patients with glomerular disease compared to purely nephrological series (corticosteroids) and undertreatment for fracture prevention, especially in nephrology consultations. This study is an immediate call to action with the dissemination of the new, more proactive, clinical guidelines, and underlines the need to standardize a coordinated and multidisciplinary care/therapeutic approach to these patients in an efficient way to avoid current discrepancies and therapeutic nihilism.
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Respiratory depression is the primary risk of mu-opioid agonists. Respiratory depression occurs more frequently in elderly or debilitated patients and in those suffering from conditions accompanied by hypoxia, hypercapnia, or upper airway obstruction, in whom even moderate therapeutic doses may significantly decrease pulmonary ventilation.
NUCYNTA™ should be administered with caution to patients with conditions accompanied by hypoxia, hypercapnia or decreased respiratory reserve such as: asthma, chronic obstructive pulmonary disease or cor pulmonale, severe obesity, sleep apnea syndrome, myxedema, kyphoscoliosis, central nervous system (CNS) depression, or coma. In such patients, even usual therapeutic doses of NUCYNTA™ may increase airway resistance and decrease respiratory drive to the point of apnea. Alternative non-mu-opioid agonist analgesics should be considered and NUCYNTA™ should be employed only under careful medical supervision at the lowest effective dose in such patients. If respiratory depression occurs, it should be treated as any mu-opioid agonist-induced respiratory depression [see Overdosage (10.2)].
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This is a prospective study from a single center. Patients will be evaluated and operated on by one of five surgeons with a subspeciality in hepato-biliary and pancreatic surgery. After thorough assessment for resectability, patients with PDAC considered resectable based on CT, but at high-risk for peritoneal disease, will be prospectively included in the study and assessed with WB-DWI/MRI within 4 weeks of the planned surgery, with the standard protocol including the following sequences: Patients will drink 1L of pineapple juice one hour prior to the examination in order to provide a negative intraluminal contrast. Patients will receive 20 mg of intravenous hyoscine butylbromide at the beginning of the MR exam in order to reduce bowel peristalsis. Sequences will include Axial et Coronal T2WI of the abdomen and pelvis, axial DWI with b values of 0, 50 and 1000 of the abdomen and pelvis, as well as Pre and post gadolinium-based contrast Axial and Coronal 3D T1WGRE. Patients with no evidence of PM on WB-DWI/MRI will be operated on and undergo pancreatic resection following the usual exploration of the peritoneal cavity in case of occult metastatic disease. Patients with suspicion of PM on WB-DWI/MRI will be approached with a diagnostic laparoscopy first, then undergo pancreatic resection if no evidence of PM is found. Each case will be followed for at least 6 months.
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Participants underwent a single CoolSculpting® treatment session on Day 1 that was comprised of timed segments of cooling followed by 2 minutes of manual massage. Each treated arm had up to two timed segments (or cycles) in the treatment session, each treated thigh had one timed segment (or cycle) in the treatment session.
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This is a prospective, paired study. Study subjects who are scheduled to undergo EUS at Mayo Clinic will be identified through Epic. Chart review will be performed including review of prior imaging, medical history, and laboratory results as available in Epic to determine study eligibility. Subjects without history of chronic liver disease (screened by low FIB-4 score) and those with known advanced fibrosis/cirrhosis will be eligible for the study. Eligible study subjects will then be contacted either before, or at the time of their endoscopy procedure to discuss study participation. All subjects will then receive standard clinical care based on the indication for the EUS procedure. During the EUS procedure, study subjects with undergo shear wave measurements obtained in a non-invasive manner as part of the endosonographic evaluation of the liver. 10 measurements (including shear wave velocity (Vs), elastic modulus (E)) will be obtained for point SWE (pSWE). Measurements will be obtained from both left and right lobes of liver unless technically infeasible to do so. Study subjects will then undergo a paired MR elastography (same day or at later date) after completion of EUS and only if consistent and reliable shear wave measurements were obtained (e.g., VsN \> 70%(reliability index of each measurement expressed in percentages), IQR/M (interquartile range/ Median) is \<15% for Vs and \<30% for E). Enrolled study subjects who had undergone a previous MRE (within 6 months of enrollment) would be eligible for the study, without the need to undergo further research MRE. After completion of MR elastography, the subjects will then continue through their routine clinical care and will not be followed up by research staff. The expected duration of subject participation is anticipated to begin at the time of study enrollment and terminate after completion of MR elastography. There will be no additional follow up.
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Each year, an estimated 69 million people suffer from traumatic brain injury/concussion worldwide. In most patients with concussion, symptoms improve within 3 months. However, in some persons, symptoms persist. The cause(s) of post-traumatic headache are not entirely clear, which limits treatment options. Sometimes, these headaches are caused by irritation to the greater occipital nerve, and pain originating from this area is called "greater occipital neuralgia". These headaches are often treated with steroid injections to the affected nerve. However, the effect of the injection is usually short lasting and may not provide adequate pain relief.
Therefore, other methods of treatment have been sought out. Platelet Rich Plasma (PRP) is an emerging biologic treatment. PRP contains high concentrations of platelets, growth factors, and anti-inflammatory molecules. PRP acts to reduce inflammation and encourage tissue repair at the site of injection. PRP is created by collecting a person's own blood, centrifuging it, and extracting the platelet-rich layer of plasma. This platelet rich mixture is then re-injected into the affected area. PRP is used as a safe and effective treatment in many fields, and is most commonly used in arthritis. PRP has recently been studied as a potential treatment for peripheral nerve disorders, such as carpal tunnel syndrome.
Post-injection, a daily headache diary provided via mobile application (Secure RedCap) available in iPhone or android device will be provided to record daily records of numeric pain rating scale, headache frequency and medication-use.
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Tamoxifen has been reported to inhibit lactation. Two placebo-controlled studies in over 150 women have shown that tamoxifen significantly inhibits early postpartum milk production. In both studies tamoxifen was administered within 24 hours of delivery for between 5 and 18 days. The effect of tamoxifen on established milk production is not known.
There are no data that address whether tamoxifen is excreted into human milk. If excreted, there are no data regarding the effects of tamoxifen in breast milk on the breastfed infant or breastfed animals. However, direct neonatal exposure of tamoxifen to mice and rats (not via breast milk) produced 1) reproductive tract lesions in female rodents (similar to those seen in humans after intrauterine exposure to diethylstilbestrol) and 2) functional defects of the reproductive tract in male rodents such as testicular atrophy and arrest of spermatogenesis.
It is not known if tamoxifen citrate is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from tamoxifen, women taking tamoxifen should not breast feed.
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FIELD: cosmetic industry; may be used as creams for skin care (day and night) and cosmetic masks. SUBSTANCE: cosmetic maricream includes gel-forming base, sodium salt of desoxyribonucleic acid prepared from fish milt, biologically active substances of vegetable and animal origin. Used as sodium salt of desoxyribonucleic acid is fragmentated acid prepared from milt of salmon family fish with average mol.m. not less 0.1MD. Composition has the following ratio of components, mas.%: sodium salt of desoxyribonucleic acid received from milt of salmon family fish with mol.m. not less 0.1MD, 0.05-0.3; base with biologically active substances of vegetable and animal origin, up to 100%. EFFECT: higher absorption through epiderma. 3 cl, 1 tbl
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Hemorrhage is the chief complication that may result from heparin therapy (see WARNINGS). An overly prolonged clotting time or minor bleeding during therapy can usually be controlled by withdrawing the drug (see OVERDOSAGE). It should be appreciated that gastrointestinal or urinary tract bleeding during anticoagulant therapy may indicate the presence of an underlying occult lesion. Bleeding can occur at any site but certain specific hemorrhagic complications may be difficult to detect:
(a) Adrenal hemorrhage, with resultant acute adrenal insufficiency, has occurred during anticoagulant therapy. Therefore, such treatment should be discontinued in patients who develop signs and symptoms of acute adrenal hemorrhage and insufficiency. Initiation of corrective therapy should not depend on laboratory confirmation of the diagnosis, since any delay in an acute situation may result in the patient’s death.
(b) Ovarian (corpus luteum) hemorrhage developed in a number of women of reproductive age receiving short- or long-term anticoagulant therapy. This complication, if unrecognized, may be fatal.
(c) Retroperitoneal hemorrhage.
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Leukocyte disorders are predominantly genetic diseases in which phagocytes fail to function normally resulting in recurrent infections. Children with these disorders are subject to recurrent, severe, often life-threatening infections and are hospitalized more frequently than their peers. Frequent hospitalization and chronic illness can affect growth, development, socialization, and educational opportunities.
Specifically, chronic granulomatous disease (CGD) is an inherited disorder in which phagocytes fail to generate an oxidative burst. In 26 patients followed at the NIH tested for behavioral problems at the request of a parent or staff member, we have observed a 23% rate of mild mental retardation. However, it is not clear whether this is due to CGD per se or the recurrent infections and hospitalizations. We seek to determine the prevalence of cognitive disabilities in children with CGD and other leukocyte disorders. We seek to determine whether abnormal leukocyte functioning may be related to specific behavioral phenotypes or impaired cognitive functioning. We also seek to clarify whether impaired cognitive functioning is related to the effects of frequent and prolonged hospitalization or other variables such as severity of illness in this population.
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Subjects aged 60 years or older at the time of the vaccination who received 1 dose of Fluarix vaccine. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
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Myelodysplastic syndrome (MDS) is a group of heterogeneous clonal disorders originating from hematopoietic stem cells, characterized by hemocytopenia and a high risk of transformation to acute myeloid leukemia (AML). The expected survival time of MDS patients varies widely, and accurate prognostic assessment is particularly important. Currently, patients with MDS are usually classified into a higher-risk group (HR-MDS) and a lower-risk group (LR-MDS) based on clinical prognostic scoring systems, but these scoring systems have certain limitations. Patients with LR-MDS account for 2/3 of MDS patients, with a lower risk of disease progression and a better prognosis, and their treatment mainly relies on erythropoiesis-stimulating agents, immunosuppressants and component transfusion. However, some LR-MDS patients still have poor prognosis, and the existing prognostic scoring systems cannot accurately evaluate their prognosis. In this review, the potential factors that may influence the prognosis of MDS patients beyond the existing assessment criteria were briefly summarized, with the aim of providing reference for the prognosis evaluation and treatment of LR-MDS patients.
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For patients who were not intubated, dexmedetomidine was infused at a rate of 0.1 microgram/kg per hour from study recruitment on the day of surgery until 8:00 am on the first day after surgery. For patients who were intubated and mechanically ventilated, dexmedetomidine infusion was started after the Richmond Agitation Sedation Scale was -2 or higher after intensive care unit admission until 8:00 am on the first day after surgery.
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SLE is a chronic, inflammatory autoimmune disorder that may affect many organ systems, including the skin, joints, and internal organs. RG2077 has been studied for use in multiple sclerosis, another autoimmune disorder. This study will evaluate the safety and efficacy of RG2077 in SLE patients who are currently receiving cyclophosphamide.
This trial is composed of two parts. The first part is a dose-escalation study in which participants will receive one of two doses of RG2077 (0.2 mg/kg or 2 mg/kg); this part of the study will last 60 days. At screening, patients will have an IV catheter inserted into their arms for administration of cyclophosphamide and RG2077. Patients will also have medical and medication history assessments, a comprehensive physical exam, and blood and urine tests. There are 5 study visits for the first part of the trial; these will occur at screening, at study entry, and Days 1, 14, and 28. Selected visits will include physical exam, vital signs measurement, blood and urine tests, and disease activity assessment. At Days 7 and 60, patients will be contacted by phone to report their medication history and any adverse effects they have experienced.
The second part of the study will evaluate a single 10 mg/kg dose of RG2077; this part of the study will last 90 days. In the study, participants will be randomly assigned to one of two groups. At the start of the study, Group 1 participants will receive RG2077 and cyclophosphamide and Group 2 participants will receive cyclophosphamide only. There will be 9 study visits; these will occur at study screening, study entry, and Days 1, 4, 7, 14, 28, and 60. At selected visits, patients will undergo physical exam, vital signs measurement, blood tests and urine tests, and disease activity assessment.
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Patients receive cyclosporine PO BID on days 1-5, verapamil hydrochloride PO QID on days 1-5, and brentuximab vedotin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
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This is a Phase 4, multi-center, open-label, randomized pragmatic superiority clinical trial comparing two strategies for initial or step-down oral therapy for complicated urinary tract infections (cUTI) without bacteremia with a uropathogen after 0-48 hours of parenteral antibiotic therapy. The trial will evaluate the success and safety of a strategy of initial or step-down fosfomycin, administered at a dose of 3 g once daily, vs. a strategy of initial or step-down levofloxacin administered at a dose of 750 mg once daily. Investigator-directed adjustment to another adequate oral therapy is allowed 1) if the causative pathogen is not susceptible in vitro to quinolone initial or step-down therapy in a subject randomized to the levofloxacin strategy, OR 2) if the subject develops an intolerance or allergy to the initial step-down oral therapy and at the investigator's discretion, OR 3) the subject has an underlying condition posing increasing risk for adverse events from quinolone therapy. The duration of oral therapy (initial + subsequent if indicated) in each strategy is 5-7 days of any per protocol antibiotic to which the pathogen is susceptible. The dosing of oral therapy depends on creatinine clearance (CrCl). The trial will enroll approximately 634 patients that are either male or female aged 18 or older with cUTI from outpatient and inpatient settings. The study will take place over 25 months in up to 15 US sites. The primary objective is to compare Strategy 1 and Strategy 2 in terms of treatment success rates at Test of Cure (TOC). The secondary objectives are: 1) to assess the safety of Fosfomycin; 2) to compare Strategy 1 and Strategy 2 in terms of solicited adverse events; 3) to compare Strategy 1 and Strategy 2 in terms of treatment success rates at End of Therapy (EOT).
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This project will build and validate a tool designed to optimize the use of magnetic resonance (MR) contrast agents for contrast-enhanced magnetic resonance angiography (CE-MRA). As with most angiography methods, contrast agents selectively highlight a patient's arteries as compared to surrounding tissue. In CE-MRA the contrast agent is injected into an arm vein using a programmable injector and transported by the body's circulation to the arteries of interest, at which point a MR acquisition depicts the arteries distinctly from surrounding soft tissue.
At present, the clinically accepted method of injecting the contrast agent is essentially the same for every patient, and has not been systematically evaluated or optimized. For most chest and abdominal CE-MRA studies contrast is injected over 5-15 seconds, and the resultant concentration of contrast agent in the arteries over the duration of the MR acquisition is not well known. What this concentration is and how it varies over time, however, has a large impact on the quality and clarity of the resulting images. This project is designed to optimize the concentration of contrast agent in the arteries during the MR scan by using the predictive results of a small "test bolus" injection to tailor the actual contrast injection for each individual patient such that concentration remains as high and as constant as possible during the time of MR acquisition. This will be accomplished by developing algorithms and software tools to tailor the optimal, patient-specific injection parameters. The method will be validated in a preliminary clinical study.
We propose that we can predict what the contrast bolus will look like (i.e., its "concentration vs. time") by first administering a small (1cc) test bolus, taking pictures as the contrast passes through the blood vessels, and analyzing the results. Using this information, we believe that an individually patient-tailored injection given in multiple phases (i.e., a "multi-phasic" injection) can create constant contrast concentration (and therefore constant signal intensity) throughout the scan, eliminating this source of image blurring, and improving the sharpness and likely the diagnostic quality of first-pass CE-MRA. Moreover, by tailoring the contrast to the duration of the scan, the contrast agent is used most efficiently and not wasted outside the acquisition duration, potentially recouping any contrast-to-noise ratio (CNR) loss. It is important to note the results of this study are generalizable to CT Angiography (CTA) as well, where similar efficient use of the contrast will reduce cost and excessive patient exposure to iodinated contrast. We plan to compare an "optimized" multiphasic contrast administration to a standard single phase contrast administration.
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Patients with benign prostatic hypertrophy may develop acute urethral obstruction. Priapism or excessive sexual stimulation may develop. Oligospermia may occur after prolonged administration or excessive dosage. If any of these effects appear, the androgen should be stopped and if restarted, a lower dosage should be utilized.
Testosterone cypionate should not be used interchangeably with testosterone propionate because of differences in duration of action.
Testosterone cypionate is not for intravenous use.
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The following discussion refers to the overall safety database of 812 patients with solid tumors treated with single-agent paclitaxel in clinical studies. Toxicities that occurred with greater severity or frequency in previously untreated patients with ovarian carcinoma or NSCLC who received paclitaxel in combination with cisplatin or in patients with breast cancer who received paclitaxel after doxorubicin/cyclophosphamide in the adjuvant setting and that occurred with a difference that was clinically significant in these populations are also described.
The frequency and severity of important adverse events for the Phase 3 ovarian carcinoma, breast carcinoma, NSCLC, and the Phase 2 Kaposi's sarcoma carcinoma studies are presented above in tabular form by treatment arm. In addition, rare events have been reported from postmarketing experience or from other clinical studies. The frequency and severity of adverse events have been generally similar for patients receiving paclitaxel for the treatment of ovarian, breast, or lung carcinoma or Kaposi's sarcoma, but patients with AIDS-related Kaposi's sarcoma may have more frequent and severe hematologic toxicity, infections (including opportunistic infections, see Table 16), and febrile neutropenia. These patients require a lower dose intensity and supportive care. (See CLINICAL STUDIES: AIDS-Related Kaposi's Sarcoma.) Toxicities that were observed only in or were noted to have occurred with greater severity in the population with Kaposi's sarcoma and that occurred with a difference that was clinically significant in this population are described. Elevated liver function tests and renal toxicity have a higher incidence in KS patients as compared to patients with solid tumors.
Hematologic: Bone marrow suppression was the major dose-limiting toxicity of paclitaxel. Neutropenia, the most important hematologic toxicity, was dose and schedule dependent and was generally rapidly reversible. Among patients treated in the Phase 3 second line ovarian study with a 3-hour infusion, neutrophil counts declined below 500 cells/mm3 in 14% of the patients treated with a dose of 135 mg/m2 compared to 27% at a dose of 175 mg/m2 (p=0.05). In the same study, severe neutropenia (<500 cells/mm3) was more frequent with the 24-hour than with the 3-hour infusion; infusion duration had a greater impact on myelosuppression than dose. Neutropenia did not appear to increase with cumulative exposure and did not appear to be more frequent nor more severe for patients previously treated with radiation therapy.
In the study where paclitaxel was administered to patients with ovarian carcinoma at a dose of 135 mg/m2/24 hours in combination with cisplatin versus the control arm of cyclophosphamide plus cisplatin, the incidences of grade IV neutropenia and of febrile neutropenia were significantly greater in the paclitaxel plus cisplatin arm than in the control arm. Grade IV neutropenia occurred in 81% on the paclitaxel plus cisplatin arm versus 58% on the cyclophosphamide plus cisplatin arm, and febrile neutropenia occurred in 15% and 4% respectively. On the paclitaxel/cisplatin arm, there were 35/1074 (3%) courses with fever in which Grade IV neutropenia was reported at some time during the course. When paclitaxel followed by cisplatin was administered to patients with advanced NSCLC in the ECOG study, the incidences of Grade IV neutropenia were 74% (paclitaxel 135 mg/m2/24 hours followed by cisplatin) and 65% (paclitaxel 250 mg/m2/24 hours followed by cisplatin and G-CSF) compared with 55% in patients who received cisplatin/etoposide.
Fever was frequent (12% of all treatment courses). Infectious episodes occurred in 30% of all patients and 9% of all courses; these episodes were fatal in 1% of all patients, and included sepsis, pneumonia and peritonitis. In the Phase 3 second-line ovarian study, infectious episodes were reported in 20% and 26% of the patients treated with a dose of 135 mg/m2 or 175 mg/m2 given as a 3-hour infusion respectively. Urinary tract infections and upper respiratory tract infections were the most frequently reported infectious complications. In the immunosuppressed patient population with advanced HIV disease and poor-risk AIDS-related Kaposi's sarcoma, 61% of the patients reported at least one opportunistic infection. (See CLINICAL STUDIES: AIDS-Related Kaposi's Sarcoma.) The use of supportive therapy, including G-CSF, is recommended for patients who have experienced severe neutropenia. (See DOSAGE AND ADMINISTRATION.)
Thrombocytopenia was reported. Twenty percent of the patients experienced a drop in their platelet count below 100,000 cells/mm3 at least once while on treatment; 7% had a platelet count <50,000 cells/mm3 at the time of their worst nadir. Bleeding episodes were reported in 4% of all courses and by 14% of all patients but most of the hemorrhagic episodes were localized and the frequency of these events was unrelated to the Paclitaxel Injection, USP dose and schedule. In the Phase 3 second-line ovarian study, bleeding episodes were reported in 10% of the patients; no patients treated with the 3-hour infusion received platelet transfusions. In the adjuvant breast carcinoma trial, the incidence of severe thrombocytopenia and platelet transfusions increased with higher doses of doxorubicin.
Anemia (Hb <11 g/dL) was observed in 78% of all patients and was severe (Hb <8 g/dL) in 16% of the cases. No consistent relationship between dose or schedule and the frequency of anemia was observed. Among all patients with normal baseline hemoglobin, 69% became anemic on study but only 7% had severe anemia. Red cell transfusions were required in 25% of all patients and in 12% of those with normal baseline hemoglobin levels.
Hypersensitivity Reactions (HSRs): All patients received premedication prior to paclitaxel (see WARNINGS and PRECAUTIONS: Hypersensitivity Reactions sections). The frequency and severity of HSRs were not affected by the dose or schedule of paclitaxel administration. In the Phase 3 second-line ovarian study, the 3-hour infusion was not associated with a greater increase in HSRs when compared to the 24-hour infusion. Hypersensitivity reactions were observed in 20% of all courses and in 41% of all patients. These reactions were severe in less than 2% of the patients and 1% of the courses. No severe reactions were observed after course 3 and severe symptoms occurred generally within the first hour of paclitaxel infusion. The most frequent symptoms observed during these severe reactions were dyspnea, flushing, chest pain, and tachycardia. Abdominal pain, pain in the extremities, diaphoresis, and hypertension were also noted.
The minor hypersensitivity reactions consisted mostly of flushing (28%), rash (12%), hypotension (4%), dyspnea (2%), tachycardia (2%), and hypertension (1%). The frequency of hypersensitivity reactions remained relatively stable during the entire treatment period.
Chills, shock, and back pain in association with hypersensitivity reactions have been reported.
Cardiovascular: Hypotension, during the first 3 hours of infusion, occurred in 12% of all patients and 3% of all courses administered. Bradycardia, during the first 3 hours of infusion, occurred in 3% of all patients and 1% of all courses. In the Phase 3 second-line ovarian study, neither dose nor schedule had an effect on the frequency of hypotension and bradycardia. These vital sign changes most often caused no symptoms and required neither specific therapy nor treatment discontinuation. The frequency of hypotension and bradycardia were not influenced by prior anthracycline therapy.
Significant cardiovascular events possibly related to single-agent paclitaxel occurred in approximately 1% of all patients. These events included syncope, rhythm abnormalities, hypertension and venous thrombosis. One of the patients with syncope treated with paclitaxel at 175 mg/m2 over 24 hours had progressive hypotension and died. The arrhythmias included asymptomatic ventricular tachycardia, bigeminy and complete AV block requiring pacemaker placement. Among patients with NSCLC treated with paclitaxel in combination with cisplatin in the Phase 3 study, significant cardiovascular events occurred in 12% to 13%. This apparent increase in cardiovascular events is possibly due to an increase in cardiovascular risk factors in patients with lung cancer.
Electrocardiogram (ECG) abnormalities were common among patients at baseline. ECG abnormalities on study did not usually result in symptoms, were not dose-limiting, and required no intervention. ECG abnormalities were noted in 23% of all patients. Among patients with a normal ECG prior to study entry, 14% of all patients developed an abnormal tracing while on study. The most frequently reported ECG modifications were non-specific repolarization abnormalities, sinus bradycardia, sinus tachycardia, and premature beats. Among patients with normal ECGs at baseline, prior therapy with anthracyclines did not influence the frequency of ECG abnormalities.
Cases of myocardial infarction have been reported. Congestive heart failure, including cardiac dysfunction and reduction of left ventricular ejection fraction or ventricular failure, has been reported typically in patients who have received other chemotherapy, notably anthracyclines. (See PRECAUTIONS: Drug Interactions section.)
Atrial fibrillation and supraventricular tachycardia have been reported.
Respiratory: Interstitial pneumonia, lung fibrosis, and pulmonary embolism have been reported. Radiation pneumonitis has been reported in patients receiving concurrent radiotherapy.
Pleural effusion and respiratory failure have been reported.
Neurologic: The assessment of neurologic toxicity was conducted differently among the studies as evident from the data reported in each individual study (see Tables 10 to 16). Moreover, the frequency and severity of neurologic manifestations were influenced by prior and/or concomitant therapy with neurotoxic agents.
In general, the frequency and severity of neurologic manifestations were dose-dependent in patients receiving single-agency paclitaxel. Peripheral neuropathy was observed in 60% of all patients (3% severe) and in 52% (2% severe) of the patients without pre-existing neuropathy. The frequency of peripheral neuropathy increased with cumulative dose. Paresthesia commonly occurs in the form of hyperesthesia. Neurologic symptoms were observed in 27% of the patients after the first course of treatment and in 34% to 51% from course 2 to 10. Peripheral neuropathy was the cause of paclitaxel discontinuation in 1% of all patients. Sensory symptoms have usually improved or resolved within several months of paclitaxel discontinuation. Pre-existing neuropathies resulting from prior therapies are not a contraindication for paclitaxel therapy.
In the Intergroup first-line ovarian carcinoma study (see Table 11), neurotoxicity included reports of neuromotor and neurosensory events. The regimen with paclitaxel 175 mg/m2 given by 3-hour infusion plus cisplatin 75 mg/m2 resulted in greater incidence and severity of neurotoxicity than the regimen containing cyclophosphamide and cisplatin, 87% (21% severe) versus 52% (2% severe), respectively. The duration of grade III or IV neurotoxicity cannot be determined with precision for the Intergroup study since the resolution dates of adverse events were not collected in the case report forms for this trial and complete follow-up documentation was available only in a minority of these patients. In the GOG first-line ovarian carcinoma study, neurotoxicity was reported as peripheral neuropathy. The regimen with paclitaxel 135 mg/m2 given by 24-hour infusion plus cisplatin 75 mg/m2 resulted in an incidence of neurotoxicity that was similar to the regimen containing cyclophosphamide plus cisplatin, 25% (3% severe) versus 20% (0% severe), respectively. Cross-study comparison of neurotoxicity in the Intergroup and GOG trials suggests that when paclitaxel is given in combination with cisplatin 75 mg/m2, the incidence of severe neurotoxicity is more common at a paclitaxel dose of 175 mg/m2 given by 3-hour infusion (21%) than at a dose of 135 mg/m2 given by 24-hour infusion (3%).
In patients with NSCLC, administration of paclitaxel followed by cisplatin resulted in a greater incidence of severe neurotoxicity compared to the incidence in patients with ovarian or breast cancer treated with single-agent paclitaxel. Severe neurosensory symptoms were noted in 13% of NSCLC patients receiving paclitaxel 135 mg/m2 by 24-hour infusion followed by cisplatin 75 mg/m2 and 8% of NSCLC patients receiving cisplatin/etoposide (see Table 15).
Other than peripheral neuropathy, serious neurologic events following paclitaxel administration have been rare (<1%) and have included grand mal seizures, syncope, ataxia, and neuroencephalopathy.
Autonomic neuropathy resulting in paralytic ileus have been reported. Optic nerve and/or visual disturbances (scintillating scotomata) have also been reported, particularly in patients who have received higher doses than those recommended. These effects generally have been reversible. However, rare reports in the literature of abnormal visual evoked potentials in patients have suggested persistent optic nerve damage. Postmarketing reports of ototoxicity (hearing loss and tinnitus) have also been received.
Convulsions, dizziness, and headache have been reported.
Arthralgia/Myalgia: There was no consistent relationship between dose or schedule of paclitaxel and the frequency or severity of arthralgia/myalgia. Sixty percent of all patients treated experienced arthralgia/myalgia; 8% experienced severe symptoms. The symptoms were usually transient, occurred two or three days after paclitaxel administration, and resolved within a few days. The frequency and severity of musculoskeletal symptoms remained unchanged throughout the treatment period.
Hepatic: No relationship was observed between liver function abnormalities and either dose or schedule of paclitaxel administration. Among patients with normal baseline liver function 7%, 22%, and 19% had elevations in bilirubin, alkaline phosphatase, and AST (SGOT), respectively. Prolonged exposure to paclitaxel was not associated with cumulative hepatic toxicity.
Hepatic necrosis and hepatic encephalopathy leading to death have reported.
Renal: Among the patients treated for Kaposi's sarcoma with paclitaxel, 5 patients had renal toxicity of grade III or IV severity. One patient with suspected HIV nephropathy of grade IV severity had to discontinue therapy. The other 4 patients had renal insufficiency with reversible elevations of serum creatinine.
Patients with gynecological cancers treated with paclitaxel and cisplatin may have an increased risk of renal failure with the combination therapy of paclitaxel and cisplatin in gynecological cancers as compared to cisplatin alone.
Gastrointestinal (GI): Nausea/vomiting, diarrhea, and mucositis were reported by 52%, 38%, and 31% of all patients, respectively. These manifestations were usually mild to moderate. Mucositis was schedule dependent and occurred more frequently with the 24-hour than with the 3-hour infusion.
In patients with poor-risk AIDS-related Kaposi's sarcoma, nausea/vomiting, diarrhea, and mucositis were reported by 69%, 79%, and 28% of patients, respectively. One-third of 43 patients with Kaposi's sarcoma complained of diarrhea prior to study start. (See CLINICAL STUDIES: AIDS-Related Kaposi's Sarcoma.)
In the first-line Phase 3 ovarian carcinoma studies, the incidence of nausea and vomiting when paclitaxel was administered in combination with cisplatin appeared to be greater compared with the database for single-agent paclitaxel in ovarian and breast carcinoma. In addition, diarrhea of any grade was reported more frequently compared to the control arm, but there was no difference for severe diarrhea in these studies.
Intestinal obstruction, intestinal perforation, pancreatitis, ischemic colitis, and dehydration have been reported. Neutropenic enterocolitis (typhlitis), despite the coadministration of G-CSF, were observed in patients treated with paclitaxel alone and in combination with other chemotherapeutic agents.
Injection Site Reaction: Injection site reactions, including reactions secondary to extravasation, were usually mild and consisted of erythema, tenderness, skin discoloration, or swelling at the injection site. These reactions have been observed more frequently with the 24-hour infusion than with the 3-hour infusion. Recurrence of skin reactions at a site of previous extravasation following administration of paclitaxel at a different site, i.e., “recall”, has been reported.
More severe events such as phlebitis, cellulitis, induration, skin exfoliation, necrosis, and fibrosis have been reported. In some cases the onset of the injection site reaction either occurred during a prolonged infusion or was delayed by a week to ten days.
A specific treatment for extravasation reactions is unknown at this time. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration.
Other Clinical Events: Alopecia was observed in almost all (87%) of the patients. Transient skin changes due to Paclitaxel Injection, USP-related hypersensitivity reactions have been observed, but no other skin toxicities were significantly associated with paclitaxel administration. Nail changes (changes in pigmentation or discoloration of nail bed) were uncommon (2%). Edema was reported in 21% of all patients (17% of those without baseline edema); only 1% had severe edema and none of these patients required treatment discontinuation. Edema was most commonly focal and disease-related. Edema was observed in 5% of all courses for patients with normal baseline and did not increase with time on study.
Skin abnormalities related to radiation recall as well as reports of maculopapular rash, pruritus, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported. In postmarketing experience, diffuse edema, thickening, and sclerosing of the skin have been reported following paclitaxel administration. Paclitaxel has been reported to exacerbate signs and symptoms of scleroderma.
Reports of asthenia and malaise have been received as part of the continuing surveillance of paclitaxel safety. In the Phase 3 trial of paclitaxel 135 mg/m2 over 24 hours in combination with cisplatin as first-line therapy of ovarian cancer, asthenia was reported in 17% of the patients, significantly greater than the 10% incidence observed in the control arm of cyclophosphamide/cisplatin.
Conjunctivitis, increased lacrimation, anorexia, confusional state, photopsia, visual floaters, vertigo, and increase in blood creatinine have been reported.
Accidental Exposure: Upon inhalation, dyspnea, chest pain, burning eyes, sore throat, and nausea have been reported. Following topical exposure, events have included tingling, burning, and redness.
To report SUSPECTED ADVERSE REACTIONS, contact Sagent Pharmaceuticals at 1-866-625-1618 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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The present invention discloses a compound of an chlorhexidine acetate local membrane forming gel, which comprises the components of the following weight percentages comprising 0.5 percentage to 7 percentage of alkyl cellulose, 1 percentage to 10 percentage of etherifying agent, 0.5 percentage to 5 percentage of cross linking agent,75 percentage to 90 percentage of dissolvent, 0.01 percentage to 3 percentage of chlorhexidine acetate. The cross linking agent is the saturated fat or the alcoholic acid, the chemical general formula of which is C<SUB>n</SUB>H<SUB>2n+2-m-l</SUB>(OH)<SUB>m</SUB>(COOH)<SUB>l</SUB>. Among the formula, m or n or 1 is the integer and the n is no less than m, which is no less than 2. 1 is no less than 0 and the result of m plus 1 is 4 to 8. The result of n plus 1 is 4 to 8. In the present invention, the compound of the chlorhexidine acetate local membrane forming gel is applied in the treatment of the local infection in the mucosa or the skin. A water drain protective membrane with smooth property, firm property, wear-resisting property and duration property is formed on the surface of the ulcer when the present invention is applied. Compared with all kinds of local formulation of the chlorhexidine acetate, the membrane formed by the gel compound is not likely to experience fracture, dissolution or corrosion. The membrane has properties of long maintenance time and slow releasing of the medicine. The membrane can be effectively maintained in the skin surface for over 8 hours and the membrane can be effectively maintained on the mouth mucosa surface for over 5 hours.
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The present invention provides a vector which can make nucleic acids to be an aggregate and locate a vector containing a cationic polymer to surround the aggregate so as to protect the nucleic acids from the enzyme. The vector comprises a polymer having branched chain(s). Preferably, 3, 4, or 6 branched chains are bonded to benzene ring. It is preferable that the number of the branched chains is higher. As the branched chain(s), a vinyl-series acrylic polymer is preferable. The vector is synthesized by reacting a dithiocarbamate compound with an acrylamide monomer for the branched chain(s).
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The present invention belongs to the technical field of medicinal preparation. The present invention provides an optical pure S-(-)-and R-(+)-omeprazole preparation and a preparation method. Proper amount of alkaline substances are added in the prepration of the present invention, such as sodium hydroxide, magnesium hydroxide, sodium phosphate, sodium carbonate, etc. so as to keep the pH value larger than 9. A certain amount of stabilizing agent is added, such as sodium sulfite, sodium thiosulfate, etc. By specific preparation methods, such as inert gas granulation, coating, drying, etc., the preparation maintains corresponding stable appearance characteristics and stable optical purity in the process of processing, storage and transportation. The preparations prepared by the present invention, such as tablets, capsule, injection, etc., are more suitable for oral application and non-intestinal tract administration so as to attain the purpose of active component treatment. The present invention has the advantages of simple process, good product stability and high finished product rate, and the solvent used in the method has no toxicity and is suitable for industrial production.
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The investigators propose a novel technology to be used at the bedside or in the field: an FDA approved diagnostic skin patch which harvests, concentrates, and stabilizes a panel of protein fragments derived from skin transudate or sweat. While drug delivery patches are routinely used, the technology proposed here has exactly the opposite function: the harvesting of diagnostic markers using novel affinity bait nanoparticles, bound within an adhesive skin patch. The proposed technology may overcome all major physiological barriers that have prevented the use of this biologic fluid for diagnostic testing. Sweat disease protein fragments are subject to rapid degradation due to proteases present in sweat and normal skin bacterial flora, and exist in extremely low abundance, far below the detection sensitivity of standard analysis platforms. Harvesting hydrogel nanoparticles are engineered with chemical high affinity baits so that they sequester the low abundance target analytes, and protect them from degradation indefinitely. Once applied to the skin, the nanoparticles in the patch harvest minute by minute, and protect from degradation, all candidate analytes in the sweat underneath the patch. The core shell bait nanoparticles are a completely novel technology that can amplify the sensitivity of protein fragment detection by 100 fold. No other technology exists that has a similar yield, concentration ability, and stabilization function. Once the collection is complete, the patch will be mailed to the diagnostic lab at room temperature. Upon receipt, the nanoparticle-captured analytes of interest can be eluted from the patch for routine measurement using any platform. Feasibility studies have demonstrated virtually 100 percent capture and 100 percent elution yield of low abundance interleukins in model sweat solutions. The investigators will collect sweat from healthy volunteers under Institutional Review Board approval. Mass spectrometry will be used to discover novel sweat protein fragments that have been concentrated and preserved in the patch. Low abundance labile protein fragments harvested from the nanoparticles will be measured by clinical immunoassays to verify sensitivity and precision. Data gathered from this study will be used to develop a foundation for sweat protein fragment testing of cutaneous disease.
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Approximately 50% of serum cefuroxime is bound to protein. Serum pharmacokinetic parameters for cefuroxime axetil tablets are shown in Table 1.
Comparative Pharmacokinetic Properties: Cefuroxime axetil for oral suspension was not bioequivalent to cefuroxime axetil tablets when tested in healthy adults. The tablet and powder for oral suspension formulations are NOT substitutable on a milligram-per-milligram basis. The area under the curve for the suspension averaged 91% of that for the tablet, and the peak plasma concentration for the suspension averaged 71% of the peak plasma concentration of the tablets. Therefore, the safety and effectiveness of both the tablet and oral suspension formulations had to be established in separate clinical trials.
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We investigated whether pediatric patients with overweight and obesity are more likely to have dyspnea compared with those who are non-overweight. We collected de-identified data from TriNetX, a global federated multicenter research database, using both the UT Southwestern Medical Center and multinational Research Networks. Our analysis focused on patients aged 8-12 years. We identified overweight and obesity using ICD-10-CM codes E66 and dyspnea using code R06.0. Patients with overweight and obesity had a significantly higher risk of dyspnea compared with those who were non-overweight. This association was observed in both the UT Southwestern Network (risk ratio: 1.81, p < 0.001) and the Research Network (risk ratio: 2.70, p < 0.001). Furthermore, within the UT Southwestern Network, the risk was found to be higher in females compared with males (risk ratio: 2.17 vs. 1.67). These results have significant clinical implications, suggesting that clinicians should consider overweight and obesity as independent risk factors for dyspnea in pediatric patients after excluding other possible contributing factors.
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The trial will be conducted in 2 consecutive stages, an exploratory (investigative) stage (Stage 1) and a proof of effectiveness stage (Stage 2). During Stage 1, a panel of 50 participants will be randomized (participants are assigned different treatments based on chance) to receive either TMC207 or placebo for 8 weeks on top of a BR. In Stage 2, another panel of 150 participants will be randomized to receive either TMC207 or placebo for 24 weeks on top of a BR. TMC207 will be dosed as 400 mg every day for the first 2 weeks, and as 200 mg 3 times/week for the following 6 or 22 weeks during Stages 1 and 2, respectively. When the participants in Stage 1 have completed 8 weeks double-blind (neither theparticipant nor the physician knows whether drug or placebo is being taken, or at what dosage) treatment with TMC207 or placebo (or have discontinued earlier), the primary Stage 1 analysis will be performed on all data of the first 8 weeks of treatment. Following this Stage 1 analysis, Stage 2 will be initiated and a panel of 150 new participants will be enrolled. After the double-blind treatment phase in both Stage 1 and Stage 2, participants will continue to receive MDR-TB treatment as per national treatment guidelines. They will be followed for safety, tolerability, pharmacokinetics, and microbiological efficacy for 96 weeks after receiving their last dose of TMC207 or placebo. The Data Safety Monitoring Board Committee will review these data on a regular basis. The DSMB/DSMC is a group of experts in tuberculosis and clinical trial conduct who have no commercial interests in the development of TMC207 and the company (Tibotec, BVBA) that is developing the new TB drug.
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Cortical thinning is an important hallmark of the maturation of brain morphology during childhood and adolescence. However, the connectome-based wiring mechanism that underlies cortical maturation remains unclear. Here, we show cortical thinning patterns primarily located in the lateral frontal and parietal heteromodal nodes during childhood and adolescence, which are structurally constrained by white matter network architecture and are particularly represented using a network-based diffusion model. Furthermore, connectome-based constraints are regionally heterogeneous, with the largest constraints residing in frontoparietal nodes, and are associated with gene expression signatures of microstructural neurodevelopmental events. These results are highly reproducible in another independent dataset. These findings advance our understanding of network-level mechanisms and the associated genetic basis that underlies the maturational process of cortical morphology during childhood and adolescence.
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Impairments in cognitive processes and their associations with dimensional measures of inattention, hyperactivity-impulsivity and anxiety were examined in children at risk of Attention-Deficit Hyperactivity Disorder. Children referred by teachers for exhibiting ADHD-type problems (n = 116; 43 meeting full diagnostic criteria for ADHD; 4-8 years) completed computerized tasks measuring episodic memory, response inhibition, visuomotor control and sustained attention, while parents were interviewed (DAWBA) to assess ADHD and anxiety symptoms. Of the 116 children assessed, 72% exhibited impaired cognitive processes; 47% had impaired visuomotor control, 37% impaired response inhibition, and 35% had impaired episodic memory. Correlational and hierarchical regression analyses using our final analytic sample (i.e., children who completed all cognitive tasks and a vocabulary assessment, n = 114) showed that poorer task performance and greater within-subject variability were significantly associated with more severe inattention symptoms but not with hyperactivity-impulsivity severity. Symptoms of separation anxiety, which were reported in over half of the sample, moderated associations between inattention and episodic memory, and between inattention and inhibition. Only children without separation anxiety showed significant correlations between ADHD symptoms and poor performance. However, separation anxiety had no moderating effect on associations between inattention and visuomotor control or sustaining attention. Children exhibiting signs of ADHD show impairments across a range of cognitive tasks. Further research to improve our understanding of these processes may be useful in the development of early interventions. Our results suggest that separation anxiety should be taken into account when considering interventions to address emerging neuropsychological deficits associated with this disorder.
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The sedation group (Group S, n=30), received 1 mg/kg ketamine and 1 mg/kg propofol as a bolus for induction. The patients then received an infusion of 100-150 mcg/kg/min propofol and 0.25mg/kg/h of ketamine for maintenance.
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Patients undergo NaF PET/CT or MDP scan within 45 days prior to cycle 1 day 1. Patients then receive standard of care Ra-223 IV on day 1 of each cycle. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo PSMA PET/CT over 45-60 minutes between 30-60 days after the last dose of Ra-223. Patients also undergo collection of blood samples during screening, on day 1 of every Ra-223 cycle, and at 30 days after the last dose of Ra-223. Patients may also undergo NaF PET/CT or MDP scans during Ra-223 treatment as clinically indicated, and/or CT scans during screening and Ra-223 treatment as clinically indicated.
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VYVGART may increase the risk of infection. The most common infections observed in Study 1 were urinary tract infection (10% of VYVGART-treated patients compared to 5% of placebo-treated patients) and respiratory tract infections (33% of VYVGART-treated patients compared to 29% of placebo-treated patients) [see Adverse Reactions (6.1) and Clinical Studies (14)]. A higher frequency of patients who received VYVGART compared to placebo were observed to have below normal levels for white blood cell counts (12% versus 5%, respectively), lymphocyte counts (28% versus 19%, respectively), and neutrophil counts (13% versus 6%, respectively). The majority of infections and hematologic abnormalities were mild to moderate in severity. Delay VYVGART administration in patients with an active infection until the infection is resolved. During treatment with VYVGART, monitor for clinical signs and symptoms of infections. If serious infection occurs, administer appropriate treatment and consider withholding VYVGART until the infection has resolved.
Immunization
Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of a new treatment cycle with VYVGART. The safety of immunization with live vaccines and the immune response to vaccination during treatment with VYVGART are unknown. Because VYVGART causes a reduction in IgG levels, vaccination with live vaccines is not recommended during treatment with VYVGART.
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Anticancer compsns. contain N-(2-ethylhexyl)-3-hydroxybutyramide (I) or its dicarboxylic acid half ester as the active ingredient together with a carrier. Synergistic anticancer compsns. contain (I) or its dicarboxylic acid half ester and adrenalin or noradrenalin. The compsns. have a positive cancer inhibiting effect at relatively low concns. and are essentially free from side effects esp. on the haematogenic and digestive organs. After prolonged treatment there is no sign of leukopenia, no loss of appetite, no nausea, no vomiting and no other adverse symptoms. LD50 of (I) = 5450 mg/kg (male mice p.o).
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The dose of verapamil hydrochloride extended-release tablets should be individualized by titration and the drug should be administered with food. Initiate therapy with 180 mg of sustained-release verapamil HCl, verapamil hydrochloride extended-release tablets, given in the morning. Lower initial doses of 120 mg a day may be warranted in patients who may have an increased response to verapamil (e.g., the elderly or small people). Upward titration should be based on therapeutic efficacy and safety evaluated weekly and approximately 24 hours after the previous dose. The antihypertensive effects of verapamil hydrochloride extended-release tablets are evident within the first week of therapy.
If adequate response is not obtained with 180 mg of verapamil hydrochloride extended-release tablets, the dose may be titrated upward in the following manner:
1. 240 mg each morning,
2. 180 mg each morning plus 180 mg each evening; or 240 mg each morning plus 120 mg each evening,
3. 240 mg every 12 hours.
When switching from immediate-release verapamil hydrochloride tablets to verapamil hydrochloride extended-release tablets, the total daily dose in milligrams may remain the same.
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This is a ambispective, multi-surgeon, single site, consecutive case series. Data collection will occur in two phases. Retrospective data collection will occur upon subject identification, and data will be collected from the site's medical records for minimum of 50 subjects who have undergone soft tissue to bone fixation with the Grappler® Interference Screw System. Data will be collected from the subjects' pre-op visits, intra-op visits, 7 week post-op follow-up visits (± 4 weeks), and 6 month post-op follow-up visits (± 4 weeks). The subject must have adequate radiographic and medical records for the minimum follow up requirement of 6 months. Prospective data collection will occur upon subject's provision of written informed consent, and data will be collected from patient reported outcomes (PRO's).
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The Sponsor provided each 170 mg dose of strontium as strontium L-lactate dry powder packaged in individual vials. The powder was prepared for consumption by adding 10 mL of distilled water to the vial and stirring until dissolution was complete. This liquid was then poured into an administration cup. An additional 10 mL of distilled water was used to rinse the remaining SrLac into the administration cup. Then 80 mL of distilled water was added directly into the administration cup. Following consumption of the 100 mL solution of SrLac, another 100 mL of distilled water was added into the administration cup, swirled, and consumed by the subject.
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It is well recognized that overall obesity increases fall risk. However, it remains unknown if the obesity-induced increase in the fall risk depends upon the adipose distribution (or obesity type: android vs. gynoid). This pilot study examined the effects of fat deposition region on fall risk following a standing-slip trial in young adults with simulated android or gynoid adiposity. Appropriate external weights were attached to two groups of healthy young lean adults at either the abdomen or upper thigh region to simulate android or gynoid adiposity, respectively, with a targeted body mass index of 32 kg/m2. Under the protection of a safety harness, both groups were exposed to an identical standing-slip on a treadmill with a maximum slip distance of 0.36 m. The primary (dynamic gait stability) and secondary (latency, length, duration, and speed of the recovery step, slip distance, and trunk velocity) outcome variables on the slip trial were compared between groups. The results revealed that the android group was more unstable with a longer slip distance and a slower trunk flexion velocity than the gynoid group at the recovery foot liftoff after the slip onset. The android group initiated the recovery step later but executed the step faster than the gynoid group. Biomechanically, the android adipose tissue may be associated with a higher fall risk than the gynoid fat tissue. Our findings could provide preliminary evidence for considering fat distribution as an additional fall risk factor to identify older adults with obesity at a high fall risk.
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Population genetics continues to identify genetic variants associated with diseases of the immune system and offers a unique opportunity to discover mechanisms of immune regulation. Multiple genetic variants linked to severe fungal infections and autoimmunity are associated with caspase recruitment domain-containing protein 9 (CARD9). We leverage the CARD9 R101C missense variant to uncover a biochemical mechanism of CARD9 activation essential for antifungal responses. We demonstrate that R101C disrupts a critical signaling switch whereby phosphorylation of S104 releases CARD9 from an autoinhibited state to promote inflammatory responses in myeloid cells. Furthermore, we show that CARD9 R101C exerts dynamic effects on the skin cellular contexture during fungal infection, corrupting inflammatory signaling and cell-cell communication circuits. Card9 R101C mice fail to control dermatophyte infection in the skin, resulting in high fungal burden, yet show minimal signs of inflammation. Together, we demonstrate how translational genetics reveals molecular and cellular mechanisms of innate immune regulation.
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Stroke is a leading cause of long-term disability, and most stroke survivors have chronic upper limb dysfunction, which affects participation in activities of daily living. In addition to conventional rehabilitation training, robot-assisted training has been advocated as a contemporary approach of hand function training. Robotic devices can be categorized into exoskeleton and end-effector types based on their mechanical design. However, previous studies did not reach an agreement on the effectiveness of two types of robot-assisted training. The study firstly proposes a hybrid robot-assisted training program, which combines two types of robotic systems, to enhance the effectiveness of robot-assisted training and provide a new approach for motor training of upper limb in stroke patients. Secondly, the relative effects of the two types of robot-assisted training will be compared. The purpose of this study is to examine the immediate and long-term effects of hybrid robot-assisted training , exoskeleton robot-assisted training , end-effector robot-assisted training , and conventional training on stroke patients' motor performance, daily life functions, quality of life, and self-efficacy. The study will recruit stroke patients and randomly assign them to the hybrid robot-assisted training, exoskeleton robot-assisted training, end-effector robot-assisted training, and conventional training groups. Each participant will receive training 3 sessions a week for 6 consecutive weeks. Participants will be assessed at baseline, after the intervention, and at 3-month follow-up. Repeated measures of analysis of variance will be used to evaluate the changes within each intervention group at three evaluation times and to compare the differences between the four intervention groups. In order to understand the motor learning effects after receiving different interventions, the investigator use kinematic analysis to investigate the movement control mechanism of upper limb movements. The findings of this study will build the evidence-based foundation for bridging the gap between basic science and clinical application.
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Fatty liver plays a pivotal role in the pathogenesis of the metabolic syndrome and type 2 diabetes. According to an updated classification, any individual with liver steatosis and one or more features of the metabolic syndrome, without excess alcohol consumption or other known causes of steatosis, has metabolic dysfunction-associated steatotic liver disease (MASLD). Up to 60-70% of all individuals with type 2 diabetes have MASLD. However, the prevalence of advanced liver fibrosis in type 2 diabetes remains uncertain, with reported estimates of 10-20% relying on imaging tests and likely overestimating the true prevalence. All stages of MASLD impact prognosis but fibrosis is the best predictor of all-cause and liver-related mortality risk. People with type 2 diabetes face a two- to threefold increase in the risk of liver-related death and hepatocellular carcinoma, with 1.3% progressing to severe liver disease over 7.7 years. Because reliable methods for detecting steatosis are lacking, MASLD mostly remains an incidental finding on imaging. Regardless, several medical societies advocate for universal screening of individuals with type 2 diabetes for advanced fibrosis. Proposed screening pathways involve annual calculation of the Fibrosis-4 (FIB-4) index, followed by a secondary test such as transient elastography (TE) for intermediate-to-high-risk individuals. However, owing to unsatisfactory biomarker specificity, these pathways are expected to channel approximately 40% of all individuals with type 2 diabetes to TE and 20% to tertiary care, with a false discovery rate of up to 80%, raising concerns about feasibility. There is thus an urgent need to develop more effective strategies for surveying the liver in type 2 diabetes. Nonetheless, weight loss through lifestyle changes, pharmacotherapy or bariatric surgery remains the cornerstone of management, proving highly effective not only for metabolic comorbidities but also for MASLD. Emerging evidence suggests that fibrosis biomarkers may serve as tools for risk-based targeting of weight-loss interventions and potentially for monitoring response to therapy.
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Effervescent compositions are disclosed, particularly effervescent compositions useful in toilet bowls. The effervescent composition may include at least one liquid or solid hydrogen peroxide source and at least one catalyst capable of catalyzing an oxidation of the hydrogen peroxide source in the presence of a liquid, such as water. Accordingly, the effervescent composition is capable of effervescence in the presence of a liquid. The effervescent composition may also include a non-hygroscopic solvent. The presence of the non-hygroscopic solvent may assist the effervescent composition in substantially avoiding effervescence until the composition contacts the liquid. Optionally, the ratio of the hydrogen peroxide source and catalyst to the non-hygroscopic solvent is not less than 9:1.
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Infertility
The effect of methadone hydrochloride on fertility is unknown. Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see Adverse Reactions (6), Clinical Pharmacology (12.2), Nonclinical Pharmacology (13.1)]. Reproductive function in human males may be decreased by methadone treatment. Reductions in ejaculate volume and seminal vesicle and prostate secretions have been reported in methadone-treated individuals. In addition, reductions in serum testosterone levels and sperm motility, and abnormalities in sperm morphology have been reported.
In published animal studies, methadone produces a significant regression of sex accessory organs and testes of male mice and rats and administration of methadone to pregnant rats reduced fetal blood testosterone and androstenedione in male offspring [see Nonclinical Toxicology (13)].
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MOTIVATION: Genome-wide association studies (GWAS) have enabled large-scale analysis of the role of genetic variants in human disease. Despite impressive methodological advances, subsequent clinical interpretation and application remains challenging when GWAS suffer from a lack of statistical power. In recent years, however, the use of information diffusion algorithms with molecular networks has led to fruitful insights on disease genes.
RESULTS: We present an overview of the design choices and pitfalls that prove crucial in the application of network propagation methods to GWAS summary statistics. We highlight general trends from the literature, and present benchmark experiments to expand on these insights selecting as case study three diseases and five molecular networks. We verify that the use of gene-level scores based on GWAS P-values offers advantages over the selection of a set of 'seed' disease genes not weighted by the associated P-values if the GWAS summary statistics are of sufficient quality. Beyond that, the size and the density of the networks prove to be important factors for consideration. Finally, we explore several ensemble methods and show that combining multiple networks may improve the network propagation approach.
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1,152,645. Rubella vaccine. MERCK & CO. Inc. 14 July, 1967 [22 May, 1967], No. 32603/67. Heading A5B. A rubella vaccine is prepared by isolating rubella virus from clinical material by inoculation of chick embryo or grivet monkey tissue culture and incubating at 30-38‹C.; successively passing the virus through culture media to attenuate the virus at least one of such passages being in media comprising minced and trypsinised 9-11 day old decapitated and amputated chick embryo culture in a cell growth medium at 30-38‹C., each passage being followed by infectivity titrations on sample harvests taken at 2-14 day intervals, the harvests being frozen until tested and re-inoculated in a culture medium if too virulent. The serial passages may include incubations in grivet monkey kidney cultures, embryonated hen's eggs or duck embryo tissue cultures.
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Intermittent fasting has become of interest for its possible metabolic benefits and reduction of inflammation and oxidative damage, all of which play a role in the pathophysiology of diabetic nephropathy. We tested in a streptozotocin (60 mg/kg)-induced diabetic apolipoprotein E knockout mouse model whether repeated fasting mimicking diet (FMD) prevents glomerular damage. Diabetic mice received 5 FMD cycles in 10 wk, and during cycles 1 and 5 caloric measurements were performed. After 10 wk, glomerular endothelial morphology was determined together with albuminuria, urinary heparanase-1 activity, and spatial mass spectrometry imaging to identify specific glomerular metabolic dysregulation. During FMD cycles, blood glucose levels dropped while a temporal metabolic switch was observed to increase fatty acid oxidation. Overall body weight at the end of the study was reduced together with albuminuria, although urine production was dramatically increased without affecting urinary heparanase-1 activity. Weight loss was found to be due to lean mass and water, not fat mass. Although capillary loop morphology and endothelial glycocalyx heparan sulfate contents were preserved, hyaluronan surface expression was reduced together with the presence of UDP-glucuronic acid. Mass spectrometry imaging further revealed reduced protein catabolic breakdown products and increased oxidative stress, not different from diabetic mice. In conclusion, although FMD preserves partially glomerular endothelial glycocalyx, loss of lean mass and increased glomerular oxidative stress argue whether such diet regimes are safe in patients with diabetes.NEW & NOTEWORTHY Repeated fasting mimicking diet (FMD) partially prevents glomerular damage in a diabetic mouse model; however, although endothelial glycocalyx heparan sulfate contents were preserved, hyaluronan surface expression was reduced in the presence of UDP-glucuronic acid. The weight loss observed was of lean mass, not fat mass, and increased glomerular oxidative stress argue whether such a diet is safe in patients with diabetes.
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Firefighters are occupational groups that work in difficult conditions both in their professional lives and during their education. These difficult conditions can lead to some negative situations on the physical and mental health of firefighters. Exposure of firefighters to smoke or chemicals during operation and training can be given as an example of their negative effects. Exposure to chemical substances also causes respiratory problems in people. The effect of the active period of firefighters on respiratory functions should be examined. This issue was emphasized while creating the study objectives. Physical performance is also extremely important for firefighters.
The assessment of physical performance will focus on training and stair climbing activity, which also provides a measure of endurance capacity in operation. In the study, the effect of the active period of firefighters on respiratory functions and stair climbing performance will be examined. In the evaluation of the effect of the active period in the profession, measurement, survey studies and some tests will be carried out in a group of volunteer firefighters. The data to be obtained from the research will be associated with the age groups of the firefighters participating in the study and the active period they spent in the profession. The effect of occupational exposure on respiratory functions and stair climbing performance will thus be determined.
Individuals who signed the Informed Consent Form will be included in the study in accordance with the inclusion and exclusion criteria from among the firefighters. The sociodemographic characteristics of the firefighters participating in the study will be questioned by using the Demographic Data Form. Pulmonary function test and respiratory muscle strength measurement will be performed with the Pony Fx pulmonary function test device. The Cornell Musculoskeletal Disorders Questionnaire will be used to evaluate musculoskeletal disorders. The 6 Minute Walk Test will be performed to evaluate exercise capacity. Stair Climbing Test will be applied to evaluate stair climbing performance.
In this study, the effect of the active period of firefighters on respiratory functions and stair climbing performance will be examined. Through the examination, its relationship with physical performance and endurance will be determined. According to the results, it is expected to determine preventive approaches to prevent problems that may occur due to the length of the active period. With this study, it is anticipated that the researchers will gain practical skills and experience related to the targeted methodologies. At the same time, it is among our goals to present the results of the study as a paper in national and international scientific congresses and to publish them as articles in scientific journals.
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We enrolled 139 internal medicine residents at 2 VA hospitals, Jesse Brown and Hines, in a randomized controlled design. Half participated in a 4 hour seminar series integrated into their ambulatory curriculum. Each month a total of 8 residents participated. Following the intervention there were 3 levels of assessment: (1) All participants, intervention and control, participated in a brief exercise interviewing 4 standardized patients (SPs). Note that we separately enlisted the assistance of 8 attending physicians to assist with case development for these SPs. (2) The research team subsequently enrolled 3 real patients from each physician's practice with "red flags" such as poor adherence, or missed visits, suggestive of contextual issues that need to be addressed. Physicians were scored on their performance at identifying the underlying contextual factors that account for these red flags and on formulating an appropriate plan of care. (3) The coders prospectively defined successful vs. unsuccessful outcomes for each case. At the follow up visit data was collected on whether the desired outcome was achieved. The analysis compared the skills, performance and outcomes of the intervention compared with the control group to determine the efficacy of training residents to individualize care.
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In this study, the toxicity of the pesticide cypermethrin and the protective properties of royal jelly against this toxicity were investigated using Allium cepa L., a model organism. Toxicity was evaluated using 6 mg/L cypermethrin, while royal jelly (250 mg/L and 500 mg/L) was used in combination with cypermethrin to test the protective effect. To comprehend toxicity and protective impact, growth, genotoxicity, biochemical, comet assay and anatomical parameters were employed. Royal jelly had no harmful effects when applied alone. On the other hand, following exposure to cypermethrin, there was a reduction in weight increase, root elongation, rooting percentage, mitotic index (MI), and chlorophyll a and b. Cypermethrin elevated the frequencies of micronucleus (MN) and chromosomal aberrations (CAs), levels of proline and malondialdehyde (MDA), and the activity rates of the enzymes catalase (CAT) and superoxide dismutase (SOD). A spectral change in the DNA spectrum indicated that the interaction of cypermethrin with DNA was one of the reasons for its genotoxicity, and molecular docking investigations suggested that tubulins, histones, and topoisomerases might also interact with this pesticide. Cypermethrin also triggered some critical meristematic cell damage in the root tissue. At the same time, DNA tail results obtained from the comet assay revealed that cypermethrin caused DNA fragmentation. When royal jelly was applied together with cypermethrin, all negatively affected parameters due to the toxicity of cypermethrin were substantially restored. However, even at the maximum studied dose of 500 mg/L of royal jelly, this restoration did not reach the levels of the control group. Thus, the toxicity of cypermethrin and the protective function of royal jelly against this toxicity in A. cepa, the model organism studied, were determined by using many different approaches. Royal jelly is a reliable, well-known and easily accessible protective functional food candidate against the harmful effects of hazardous substances such as pesticides.
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PURPOSE:To provide an oral solution stably containing icariin for long period by compounding a nonionic surfactant. CONSTITUTION:A nonionic surfactant, preferably 0.05-5.0wt.% of a polyoxyalkylene group-having ester or ether type surfactant such as polyoxyethylene glycol fatty acid ester or polyoxyethylene hardened castor oil is added to an oral solution containing icariin which is an active ingredient of Epimedium grandiflorum Morr var. thunbergianum and which has been reported to have functions such as antibody production-accelerating activity and sthenia tonic activity. The icariin may be prepared in the form of a tincture, solution extract, soft extract or dried extract obtained by the extraction of the Epimedium grandiflorum Morr war. thunbergianum. The oral solution is prepared in the form of a solution, emulsion or suspension, and the pH of the oral solution is preferably 2.5 to < 4 especially 2.5 to 3.5.
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BACKGROUND: The proliferation potential of mammalian cardiomyocytes declines markedly shortly after birth. Both long non-coding RNAs (lncRNAs) and mRNAs demonstrate altered expression patterns during cardiac development. However, the role of lncRNAs in the cell cycle arrest of cardiomyocytes remains inadequately understood.
METHOD: The expression pattern of lncRNAs and mRNAs was analyzed in mouse hearts exhibiting varying regenerative potentials on postnatal days (P) 1, 7, and 28. Weighted correlation network analysis (WGCNA) was employed to elucidate the co-expression relationship between lncRNAs and mRNAs. Protein-protein interaction (PPI) network was built using the STRING database, and hub lncRNAs were identified by CytoHubba. Molecular Complex Detection (MCODE) was used to screen core modules of the PPI network in Cytoscape. Upstream lncRNAs and miRNAs which may regulate mRNAs were predicted using miRTarBase and AnnoLnc2, respectively. Myocardial infarction (MI) was induced by ligation of the left anterior descending coronary artery.
RESULTS: Compared with the P1 heart, 618 mRNAs and 414 lncRNAs displayed. transcriptional changes in the P7 heart, while 2358 mRNAs and 1290 lncRNAs showed from P7 to P28. Gene Ontology (GO) analysis revealed that module 1 in the both comparisons was enriched in the mitotic cell cycle process. 2810408I11Rik and 2010110K18Rik were identified as hub lncRNAs and their effects on the proliferation of cardiomyocytes were verified in vitro. Additionally, four lncRNA-miRNA-mRNA regulatory axes were predicted to explain the mechanism by which 2810408I11Rik and 2010110K18Rik regulate cardiomyocyte proliferation. Notably, the overexpression of 2810408I11Rik enhances cardiomyocyte proliferation and heart regeneration in the adult heart following MI.
CONCLUSION: This study systematically analyzed the landscape of lncRNAs and mRNAs at P1, P7, and P28. These findings may enhance our understanding of the framework for heart development and could have significant implications for heart regeneration.
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Enzymatic analysis of aspartate/alanine aminotransferase (AST/ALT) does not exactly represent the progression of liver fibrosis. Immunoassay for the AST (cytoplasmic \[c\] AST/mitochondrial \[m\] AST) and ALT (ALT1/ALT2) have been suggested as one of the alternatives for the enzy-matic analysis. We evaluated the efficacy of immunoassay in predicting liver fibrosis and in-flammation. A total of 219 patients with chronic hepatitis B (CHB) who underwent hepatic ve-nous pressure gradient (HVPG) and liver biopsy before antiviral therapy were recruited. Serum samples were prepared from blood during HVPG. The liver function test including enzymatic AST/ALT and immunological cAST, mAST, ALT1 and ALT2 were checked with sandwich ELI-SA immunoassay with fluorescence labeled monoclonal antibodies, and were compared with the METAVIR stage of live fibrosis and the Knodell grade of inflammation.
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The present invention relates to a recipe product which contains xanthophyll and/or carotene and has the effects of protecting eyes, eyesight, etc. and the preparation method of the product, particularly an acceptable preparation, such as soft capsules, drop pills, liquid agents, etc., for protecting vision and preventing or treating eye diseases, cancers, prostate hyperplasia, aging delay, etc. and the preparation method of the preparation. The preparation essentially contains functional components of xanthophyll and/or carotene, gamma-linolenic acid, alpha-linolenic acid and pharmaceutic adjuvant as the rest. A recipe comprises the effective components of the following weight proportion: 0.5% to 20% of the xanthophyll, 0% to 40% of the Beta-Carotene, 0.8%to 30% of the gamma-linolenic acid and 0.5% to 70% of the alpha-linolenic acid. The use dosage of a prepared finished product every time contains the components of the weight proportion: 1 to 10 mg of the xanthophyll, 0 to 20 mg of the carotene, 4 to 150 mg of the gamma-linolenic acid, 2.5 to 350 mg of the alpha-linolenic acid and adjuvant as the rest. In addition, the preparation contains other solvent stroma composed of one or multiple kinds of plant edible or medicinal oil, such as single and/or polyunsaturated fatty acid of oleic acid, linoleic acid, etc.
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The invention provides a biological fermentation primary liquid mask and a preparation method and a storing method thereof and belongs to the field of cosmetics. The biological fermentation primary liquid mask is free of a carrier, is attached to the face and free of washing. The biological fermentation primary liquid mask is formed in the mode that blueberries, ginseng, roses, chamomile, soybean and tremella are decocted and fermented. The preparation method comprises the following steps that raw materials are screened, weighed and cleaned in sequence and then mixed, water is added, decocting is conducted, cooling and filtering are conducted, a product is poured into a mould containing original fungi, and then fermentation is conducted for 5-7 days at the temperature of 30-32 DEG C with the humidity being 40%-45% in an air atmosphere; in this way, the biological fermentation primary liquid mask is obtained, wherein the pH value is about 6.8. The storing method of the biological fermentation primary liquid mask comprises the steps that the mask is stored in storage liquid, sealed in vacuum and then stored in a shady, cool and dry place, wherein the storing liquid comprises lemon hydrosol, tea tree hydrosol, lavender hydrosol and mycose. The biological fermentation primary liquid mask achieves the purposes of whitening skin, removing beverage, redness, acne and wrinkles, shrinking pores, eliminating fat granules, improving dark and dry skin, removing dead skin and the like at a time.
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Practitioners should give the following information and instructions to patients receiving barbiturates.
1. The use of barbiturates carries with it an associated risk of psychological and/or physical dependence. The patient should be warned against increasing the dose of the drug without consulting a physician.
2. Barbiturates may impair mental and/or physical abilities required for the performance of potentially hazardous tasks (e.g., driving, operating machinery, etc.).
3. Alcohol should not be consumed while taking barbiturates. Concurrent use of the barbiturates with other CNS depressants (e.g., alcohol, narcotics, tranquilizers, and antihistamines) may result in additional CNS depressant effects.
4. Effect of anesthetic and sedation drugs on early brain development
Studies conducted in young animals and children suggest repeated or prolonged use of general anesthetic or sedation drugs in children younger than 3 years may have negative effects on their developing brains. Discuss with parents and caregivers the benefits, risks, and timing and duration of surgery or procedures requiring anesthetic and sedation drugs. Because some animal data suggest that the window of vulnerability includes the 3rd trimester of pregnancy, discuss with pregnant women the benefits, risks, and timing and duration of surgery or procedures requiring anesthetic and sedation drugs. (See “Warnings-Pediatric Neurotoxicity”.)
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Physicians should discuss with patients the contraindication of tadalafil with regular and/or intermittent use of organic nitrates. Patients should be counseled that concomitant use of tadalafil with nitrates could cause blood pressure to suddenly drop to an unsafe level, resulting in dizziness, syncope, or even heart attack or stroke.
Physicians should discuss with patients the appropriate action in the event that they experience anginal chest pain requiring nitroglycerin following intake of tadalafil tablets. In such a patient, who has taken tadalafil tablets, where nitrate administration is deemed medically necessary for a life-threatening situation, at least 48 hours should have elapsed after the last dose of tadalafil tablets before nitrate administration is considered. In such circumstances, nitrates should still only be administered under close medical supervision with appropriate hemodynamic monitoring. Therefore, patients who experience anginal chest pain after taking tadalafil tablets should seek immediate medical attention [see Contraindications ( 4.1) and Warnings and Precautions ( 5.1)] .
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BACKGROUND: In 2021, a new Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equation was introduced that excluded race correction. We set out to compare estimated glomerular filtration rate (eGFR) determined using the creatinine-based CKD-EPI 2009 and 2021 equations and the reclassification of chronic kidney disease (CKD) eGFR staging to explore the potential ramifications of adopting the 2021 equation on reported eGFR and CKD staging.
METHODS: We analyzed secondary data previously utilized to determine reference intervals among Black African individuals residing in urban towns in Kenya. Serum creatinine was measured using a standardized modified Jaffé kinetic method on a Beckman AU5800 analyzer. Glomerular filtration rate (GFR) was estimated using both the 2009 and 2021 CKD-EPI creatinine equations. Classification of CKD based on eGFR was performed using the Kidney Disease: Improving Global Outcomes (KDIGO) practice guidelines.
RESULTS: Using 533 study samples, the median eGFR was highest when determined using the race-corrected CKD-EPI 2009 equation. The CKD-EPI 2021 equation yielded a median eGFR that was similar to the non-race-corrected CKD-EPI 2009 equation. The race-corrected CKD-EPI 2009 equation classified 93.6% of participants into CKD stage G1 compared with 85.6% by the CKD-EPI 2021 equation. The CKD-EPI 2021 equation classified 14.3% of participants into CKD stage G2 compared to 6.4% by the race-corrected CKD-EPI 2009 equation.
CONCLUSIONS: The CKD-EPI 2021 equation gave a comparable eGFR to the non-race-corrected CKD-EPI 2009 equation and its implementation in laboratories reporting eGFR in Kenya will help in identifying patients with an appropriate decrease in renal function.
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Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogue inhibitors, including entecavir, alone or in combination with antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside inhibitor exposure may be risk factors. Particular caution should be exercised when administering nucleoside analogue inhibitors to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors.
Lactic acidosis with entecavir use has been reported, often in association with hepatic decompensation, other serious medical conditions, or drug exposures. Patients with decompensated liver disease may be at higher risk for lactic acidosis. Treatment with entecavir should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
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On CB CGM patients, CGM data will also be transmitted from the bedside smartphone to the Digital Dashboard. The Digital Dashboard will integrate CGM data for CB CGM's participants for presentation via two views: (1) Real-Time Management and (2) Clinical Optimization. Telemetry technicians to conduct site-based monitoring, and the Diabetes APN will conduct remote management of patients at the site from a central, Scripps Diabetes Hub, per below. (Note, as CGMs are not FDA-approved for in-hospital glucose management, CB CGM participants will also have their glucose monitored via the hospital's standard POC testing protocol described for UC).
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The present invention provides a novel antibody fragment based antifungal conjugate selectively targeting Candida spp. comprising of at least one antimicrobial peptide at one end of the conjugate, more particularly, human Histatin-5; an antibody fragment at the other end of the conjugate, specific against Candida spp. enolase, a virulence factor protease and biofilm specific antigen of Candida spp.; at least one signal protease cleavage sequence susceptible to cleavage by virulent protease secreted by Candida spp., secreted aspartyl proteinase-1 (SAP1); and at least one flexible polypeptide linker. The signal protease cleavage sequence and the flexible polypeptide linker are in tandem with each other and placed in between the antimicrobial peptide and the antibody. The in vitro MIC-99 of the conjugate against Candida spp., is in the range of 0.2-0.3 μM, more specifically, 0.25 μM or 250 nM.
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