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Fragile X syndrome (FXS) is caused by the full mutation in the FMR1 gene on the Xq27.3 chromosome region. It is the most common monogenic cause of autism spectrum disorder (ASD) and inherited intellectual disability (ID). Besides ASD and ID and other symptoms, individuals with FXS may exhibit sleep problems and impairment of circadian rhythm (CR). The Drosophila melanogaster models of FXS, such as dFMR1B55, represent excellent models for research in the FXS field. During this study, sleep patterns and CR in dFMR1B55 mutants were analyzed, using a new platform based on continuous high-resolution videography integrated with a highly-customized version of an open-source software. This methodology provides more sensitive results, which could be crucial for all further research in this model of fruit flies. The study revealed that dFMR1B55 male mutants sleep more and can be considered weak rhythmic flies rather than totally arrhythmic and present a good alternative animal model of genetic disorder, which includes impairment of CR and sleep behavior. The combination of affordable videography and software used in the current study is a significant improvement over previous methods and will enable broader adaptation of such high-resolution behavior monitoring methods. [ABSTRACT FROM AUTHOR]

Background: Hypothyroidism is a chronic disease, affecting almost all body functions, associated with deficiency in the thyroid hormones T4 and T3. Though different clinical practice guidelines available, but lots of inconsistency still exists in treatment practices by different physicians across different specialties. This study was conducted with an aim to document and report current clinical practices for managing hypothyroidism. Materials &Methods: A cross-sectional survey was conducted in 30 practicing doctors including family physicians/ general practitioners /primary care physicians, endocrinologists and doctors of other specialties practicing in and around Kolkata, West Bengal, India. Pre-designed validated questionnaire was used after necessary modification in view of pilot study to evaluate the clinical practice patterns for managing hypothyroidism in this study. Results: About 36.67% of participating doctors were practicing gradual restoration of euthyroidism, whereas 26.67% were of the opinion to prescribe an empiric dose and there after adjusting the dose to achieve target thyroid hormone levels and 36.67% agreed that they would start with a calculated full-replacement dose from the beginning. About 54% would increase in increments of 25 microgram during gradual restoration of euthyroidism. Approx. 90% would use a brand name of L-T4. 45% would recheck thyroid hormone levels 6 weeks after starting therapy and 56% would obtain laboratory studies at 3-month intervals. In patient planning pregnancy, the preferred TSH target was 1.0 to 1.4 mU/L (40%) while 60% would continue the current dose of LT4 during pregnancy. In subclinical hypothyroidism, positive TPO antibodies and symptoms of hypothyroidism constitute the main determinants for initiating treatment. Conclusion: The survey revealed both alignment and focal deviation from recent Clinical practice guidelines. [ABSTRACT FROM AUTHOR]

The concentration of persistent organic compounds, including pesticides, in aquatic environments is gradually increasing due to industrial discharge and uncontrolled runoff from agricultural fields. The advanced oxidation process is considered the most effective treatment method for the mineralization of persistent compounds. This research focused on the degradation of 2,4-dichlorophenoxyacetic acid (2,4-D) herbicide by a homogeneous process involving ultraviolet irradiation and H2O2 (UV–H2O2) and utilized response surface methodology (RSM) to analyzed influences of key factors involved in processes like 2,4-D concentration, H2O2 dose, pH, and nitrate amount in wastewater. Results showed that 90% of the 2,4-D herbicide was degraded within 5 min of UV-C radiation (253.7 nm wavelength) corresponding to the peroxide dose of 2 mol H2O2/mol 2,4-D at pH 5 and a nitrate concentration of 0.25 mM. A polynomial quadratic equation was developed to envisage both time- and fluence-based rate constants. All process parameters were found to significantly affect the degradation of the herbicide. Results indicated that an increase in initial 2,4-D and nitrate concentration in solution decreases the 2,4-D degradation rate. Higher H2O2 dosages and pH levels indicated an intensification in the rate constant up to an optimum value. Further, an increase in H2O2 dosage and pH resulted in a decrease in degradation rate. Further, the optimum conditions for 2,4-D degradation by the UV–H2O2 process were estimated. The findings of the present work will help to design the treatment process in real field conditions with variable water matrices. [ABSTRACT FROM AUTHOR]

This article presents a study comparing the performance of students in theory and practical components of a final pharmacology examination under two different curricula: non-competency-based medical education (Non-CBME) and competency-based medical education (CBME). The study aims to evaluate the effects of implementing CBME on students' knowledge acquisition, clinical performance, and preparedness for practice. However, the article does not provide any specific findings or results from the study. [Extracted from the article]

Mitochondrial topisomerase 1 (Top1mt) is critical for mtDNA replication, transcription, and energy production. Here, we investigate the carrier-mediated targeted delivery of the anticancer drug irinotecan into the mitochondria to selectively trap Top1mt covalent complexes (Top1mtcc) and its role in anticancer therapeutics. We have designed a biocompatible mesoporous metal–organic framework (MOF) material, namely MIL-101(Fe), as the drug delivery carrier that selectively localizes inside mitochondria. In contrast to the traditional way of synthesising MOFs, here we have employed a vapour-assisted solvothermal method for the synthesis of MIL-101(Fe) using terephthalic acid as the organic linker and Fe(III) as the metal source. The advantage of this method is that it recycles the excess solvent (DMF) and reduces the amount of washing solvent. We demonstrate that MIL-101(Fe)-encapsulated irinotecan (MIL-Iri) was selectively targeted towards the mitochondria to poison Top1mtcc in a dose-dependent manner and was achieved at a low nanomolar drug concentration. We provide evidence that Top1mtcc generated by MIL-Iri leads to mtDNA damage in human colon and breast cancer cells and plays a significant role in cellular toxicity. Altogether, this study provides evidence for a new and effective strategy in anticancer chemotherapy. [ABSTRACT FROM AUTHOR]

We present an algorithm for producing Delaunay triangulations of manifolds. The algorithm can accommodate abstract manifolds that are not presented as submanifolds of Euclidean space. Given a set of sample points and an atlas on a compact manifold, a manifold Delaunay complex is produced for a perturbed point set provided the transition functions are bi-Lipschitz with a constant close to 1, and the original sample points meet a local density requirement; no smoothness assumptions are required. If the transition functions are smooth, the output is a triangulation of the manifold. The output complex is naturally endowed with a piecewise-flat metric which, when the original manifold is Riemannian, is a close approximation of the original Riemannian metric. In this case the output complex is also a Delaunay triangulation of its vertices with respect to this piecewise-flat metric., Author(s): Jean-Daniel Boissonnat [sup.1] , Ramsay Dyer [sup.1] , Arijit Ghosh [sup.2] Author Affiliations: (Aff1) 0000 0001 2186 3954, grid.5328.c, INRIA, DataShape, , Sophia-Antipolis, France (Aff2) 0000 0001 2157 0617, [...]