Mohamadkrogh4315

Schizophrenia (SZ) is a serious neurodevelopmental disorder. As the etiology of SZ is complex and the pathogenesis is not thoroughly understood, the diagnosis of different subtypes still depends on the subjective judgment of doctors. Therefore, there is an urgent need to develop early objective laboratory diagnostic biomarkers to screen different subtypes of patients as early as possible, and to implement targeted prevention and precision medicine to reduce the risk of SZ and improve patients' quality of life. In this study, untargeted metabolomics and 16S rDNA sequencing were used to analyze the differences in metabolites and gut microflora among 28 patients with two types of schizophrenia and 11 healthy subjects. The results showed that the metabolome and sequencing data could effectively discriminate among paranoid schizophrenia patients, undifferentiated schizophrenia patients and healthy controls. We obtained 65 metabolites and 76 microorganisms with significant changes, and fecal metabolite composition was significantly correlated with the differential genera (|r|>0.5), indicating that there was a regulatory relationship between the gut microbiota and the host metabolites. The gut microbiome, as an objective and measurable index, showed good diagnostic value for distinguishing schizophrenia patients from healthy people, especially with a combination of several differential microorganisms, which had the best diagnostic effect (AUC>0.9). Our results are conducive to understanding the complicated metabolic changes in SZ patients and providing valuable information for the clinical diagnosis of SZ.

Obstructive sleep apnea (OSA) is an important risk factor for poor asthma control. The objective of this study is to analyze the symptomatic control in asthmatic patients with OSA after using continuous positive airway pressure (CPAP).

Patients were collected in a monographic asthma consult and a polygraphy was performed due to clinical suspicion or poor disease control. Asthma associated pathologies, as well as clinical and patient-perceived asthma control parameters were evaluated before and after the initiation of CPAP.

A hundred patients were included, 59% were women and 41% men. From them, 54% had severe OSA, 33% moderate OSA and 13% mild OSA, and 10% could not tolerate CPAP. Eighty four percent had a moderate or severe degree of asthma with fractional exhaled nitric oxide (FENO) 32±24.6ppm and an asthma control test (ACT) before CPAP of 19±4. Asthma control before CPAP was good in 41% of patients, partial in 29%, and bad in 30%. After three or more months of CPAP, clinical asthma control was good in 70% (p<0.001), perceived control by ACT after CPAP was 21±4 (p<0.001). When asked for their opinion, 51.5% referred clinical improvement after CPAP, no change in 46.5%.

The use of CPAP in asthmatic patients with OSA improves both clinical and perceived asthma control in a statistically significant way. Most patients had good adaptation to CPAP (90%) and 51.5% had clinical improvement.

The use of CPAP in asthmatic patients with OSA improves both clinical and perceived asthma control in a statistically significant way. Most patients had good adaptation to CPAP (90%) and 51.5% had clinical improvement.

Calculation of the Size Specific Dose Estimate (SSDE) requires accurate delineation of the skin boundary of patient CT slices. The AAPM recommendation for SSDE evaluation at every CT slice is too time intensive for manual contouring, prohibiting real-time or bulk processing; an automated approach is therefore desirable. Previous automated delineation studies either did not fully disclose the steps of the algorithm or did not always manage to fully isolate the patient. The purpose of this study was to develop a validated, freely available, fast, vendor-independent open-source tool to automatically and accurately contour and calculate the SSDE for the abdomino-pelvic region for entire studies in real-time, including flagging of patient-truncated images.

The Python tool, CTContour, consists of a sequence of morphological steps and scales over multiple cores for speed. Tool validation was achieved on 700 randomly selected slices from abdominal and abdomino-pelvic studies from public datasets. Contouring accuracy was assessed visually by four medical physicists using a 1-5 Likert scale (5 indicating perfect contouring). SQ22536 ic50 Mean SSDE values were validated via manual calculation.

Contour accuracy validation produced a score of four of five for 98.5% of the images. A 300 slice exam was contoured and truncation flagged in 6.3s on a six-core laptop.

The algorithm was accurate even for complex clinical scenarios and when artefacts were present. Fast execution makes it possible to automate the calculation of SSDE in real time. The tool has been published on GitHub under the GNU-GPLv3 license.

The algorithm was accurate even for complex clinical scenarios and when artefacts were present. Fast execution makes it possible to automate the calculation of SSDE in real time. The tool has been published on GitHub under the GNU-GPLv3 license.Domestic water insecurity harms quality of life outcomes beyond health, for example in worry about water availability or anger at disrupted plans. However, these outcomes are excluded from cost-benefit analyses of water supply interventions, which typically measure and value only prevented disease and time savings. In this paper, I propose a means of quantifying the value of being water secure for an individual's quality of life, the water-adjusted person year (WAPY). One WAPY represents a year lived in complete water security. It is inspired by the quality-adjusted life year in health economics, which combines time with a health-related quality of life index. The WAPY combines time using water services with a water-related quality of life (WaterQoL) index, where 0 = completely water insecure and 1 = completely water secure. The index could be derived from an existing four-attribute Water Insecurity Experiences scale, which includes questions such as "how often did you worry that you would not have enough water for all of your needs?". Other questions concern drinking water, disrupted plans, and handwashing. Responses can be combined in a weighted index based on the relative importance of the four attributes to people. If someone has a WaterQoL index of 0.6, over a 10 year period they would have 6 WAPYs. If a water supply intervention raised WaterQoL to 0.8, they would gain 2 WAPYs over 10 years. The monetary value of WAPYs gained (e.g. in US$) could be estimated by willingness to pay and included in a cost-benefit analysis. Some interventions might result in greater WaterQoL gains than others, or longer-lasting services. Incorporating WAPYs in cost-benefit analyses, alongside prevented disease and time savings, could help identify interventions which provide better water services to more people within a given budget.Dabigatran etexilate (DABE), an oral anticoagulant prodrug, is nearly completely metabolized to the dabigatran (DAB) active metabolite by carboxylesterase-1 (CES1) and carboxylesterase-2 (CES2). The high interpatient variation in DAB plasma concentrations, coupled with its low therapeutic index, emphasizes the need to understand how CES1 and CES2 impact active metabolite formation. Previous work focused on CES1 enzyme activity but the contributions of CES2 remain unclear. The purpose of this study was to determine how CES2 activity influences DAB active metabolite formation. We compared the efficiency of DAB formation from DABE when exposed sequentially to human intestinal and then human hepatic microsomes (mimicking the normal metabolic sequence) with the reverse metabolic sequence in which DABE is exposed to hepatic and then intestinal microsomes. The poor efficiency of DAB formation with reverse sequential hydrolysis indicates that CES2 activity is crucial for active metabolite formation. Thus, the decrease in DAB formation with normal sequential hydrolysis was more sensitive to CES2 inhibition by verapamil (CES2 IC50 = 3.4 μM) than CES1 inhibition by diltiazem (CES2 IC50 = 9.1 μM). These results show CES2 activity plays a crucial role in DAB formation and that variability in its activity is an important determinant of therapeutic response.

Prior to dolutegravir availability, ritonavir-boosted lopinavir (LPV/r) was an alternative recommendation when first-line drugs could not be used. A high concentration of protease inhibitors was observed in the Thai people living with HIV (PLWH). Thus, dose reduction of LPV/r may be possible. However, the pharmacokinetics and dose optimization of LPV/r have never been investigated. This study aimed to develop a population pharmacokinetic model of LPV/r and provide dosage optimization in Thai PLWH.

LPV and RTV trough concentrations from Thai PLWH were combined with intensive data. The data were analyzed by the nonlinear mixed-effects modeling approach. The influence of RTV concentration on LPV oral clearance (CL/F) was investigated.

Rifampicin (RIF) use increased LPV and RTV CL/F by 2.16-fold and 1.99-fold, respectively. The reduced dose of 300/75 and 200/150mg twice daily provided a comparable percentage of patients achieving LPV target trough concentration to the standard dose for PI-naïve patients. For HIV/TB co-infected patients receiving RIF who could not tolerate the recommended dose, the reduced dose of 600/150mg twice daily was recommended.

The population pharmacokinetic model was developed by integrating the interaction between LPV and RTV. The reduced LPV/r dosage offers sufficient LPV exposure for Thai PLWH.

The population pharmacokinetic model was developed by integrating the interaction between LPV and RTV. The reduced LPV/r dosage offers sufficient LPV exposure for Thai PLWH.Microalgae, the primary producers in water ecosystems, are the main food of fish and shrimp. Microalgae have a great capacity to absorb heavy metals, and low concentrations of heavy metals can promote the growth of them. But high concentrations have a strong influence on the physiological and biochemical processes in algae, such as growth, photosynthesis, cell ultrastructure, protein content and fatty acid composition. Heavy metals may also induce the formation of reactive oxygen species (ROS), which causes the oxidation damage of protein, lipid and thiol peptides, and activates the antioxidant system. Heavy metals can be removed or converted into another state by biosorption of cell surface, accumulation in cells, combining with antioxidant enzymes and so on. This review summarized the responses of microalgae to heavy metals and comprehensively described the removal and tolerance mechanisms by extracellular adsorption and intracellular accumulation, which are helpful to treat pollution and improve the culture of microalgae.Induction of diabetes mellitus by streptozotocin (STZ) in rats at birth is of high mortality and low success rate when male puppies are separated from females, prioritizing females breastfeeding. Cross-parental care of the entire litter and SZT-induced diabetes up to 12 h post-birth become with high success rate, low animal death, and females with glycaemia >140 mg/dL on the 90 postnatal day. Cross-parental care is more effective in STZ-induction of diabetes, which is maintained during pregnancy (diabetes in pregnancy), than the conventional protocol of male separation at birth.