Dosing pole recommendations for lymphatic filariasis elimination: A height-weight quantile regression modeling approach

BACKGROUND: The World Health Organization (WHO) currently recommends height or age-based dosing as alternatives to weight-based dosing for mass drug administration lymphatic filariasis (LF) elimination programs. The goals of our study were to compare these alternative dosing strategies to weight-based dosing and to develop and evaluate new height-based dosing pole scenarios. METHODOLOGY/PRINCIPAL FINDINGS: Age, height and weight data were collected from \u3e26,000 individuals in five countries during a cluster randomized LF clinical trial. Weight-based dosing for diethylcarbamazine (DEC; 6 mg/kg) and ivermectin (IVM; 200 ug/kg) with tablet numbers derived from a table of weight intervals was treated as the gold standard for this study. Following WHO recommended age-based dosing of DEC and height-based dosing of IVM would have resulted in 32% and 27% of individuals receiving treatment doses below those recommended by weight-based dosing for DEC and IVM, respectively. Underdosing would have been especially common in adult males, who tend to have the highest LF prevalence in many endemic areas. We used a 3-step modeling approach to develop and evaluate new dosing pole cutoffs. First, we analyzed the clinical trial data using quantile regression to predict weight from height. We then used weight predictions to develop new dosing pole cutoff values. Finally, we compared different dosing pole cutoffs and age and height-based WHO dosing recommendations to weight-based dosing. We considered hundreds of scenarios including country- and sex-specific dosing poles. A simple dosing pole with a 6-tablet maximum for both DEC and IVM reduced the underdosing rate by 30% and 21%, respectively, and was nearly as effective as more complex pole combinations for reducing underdosing. CONCLUSIONS/SIGNIFICANCE: Using a novel modeling approach, we developed a simple dosing pole that would markedly reduce underdosing for DEC and IVM in MDA programs compared to current WHO recommended height or age-based dosing

The adult heart responds to increased workload with physiologic hypertrophy, cardiac stem cell activation, and new myocyte formation

Aims It is a dogma of cardiovascular pathophysiology that the increased cardiac mass in response to increased workload is produced by the hypertrophy of the pre-existing myocytes. The role, if any, of adult-resident endogenous cardiac stem/progenitor cells (eCSCs) and new cardiomyocyte formation in physiological cardiac remodelling remains unexplored. Methods and results In response to regular, intensity-controlled exercise training, adult rats respond with hypertrophy of the pre-existing myocytes. In addition, a significant number (∼7%) of smaller newly formed BrdU-positive cardiomyocytes are produced by the exercised animals. Capillary density significantly increased in exercised animals, balancing cardiomyogenesis with neo-angiogenesis. c-kitpos eCSCs increased their number and activated state in exercising vs. sedentary animals. c-kitpos eCSCs in exercised hearts showed an increased expression of transcription factors, indicative of their commitment to either the cardiomyocyte (Nkx2.5pos) or capillary (Ets-1pos) lineages. These adaptations were dependent on exercise duration and intensity. Insulin-like growth factor-1, transforming growth factor-β1, neuregulin-1, bone morphogenetic protein-10, and periostin were significantly up-regulated in cardiomyocytes of exercised vs. sedentary animals. These factors differentially stimulated c-kitpos eCSC proliferation and commitment in vitro, pointing to a similar role in vivo. Conclusion Intensity-controlled exercise training initiates myocardial remodelling through increased cardiomyocyte growth factor expression leading to cardiomyocyte hypertrophy and to activation and ensuing differentiation of c-kitpos eCSCs. This leads to the generation of new myocardial cells. These findings highlight the endogenous regenerative capacity of the adult heart, represented by the eCSCs, and the fact that the physiological cardiac adaptation to exercise stress is a combination of cardiomyocyte hypertrophy and hyperplasia (cardiomyocytes and capillaries)

Importance of Spin-Orbit Interaction for the Electron Spin Relaxation in Organic Semiconductors

Despite the great interest organic spintronics has recently attracted, there is only a partial understanding of the fundamental physics behind electron spin relaxation in organic semiconductors. Mechanisms based on hyperfine interaction have been demonstrated, but the role of the spin-orbit interaction remains elusive. Here, we report muon spin spectroscopy and time-resolved photoluminescence measurements on two series of molecular semiconductors in which the strength of the spin-orbit interaction has been systematically modified with a targeted chemical substitution of different atoms at a particular molecular site. We find that the spin-orbit interaction is a significant source of electron spin relaxation in these materials

Consequence of UV Irradiation on the Zirconium Tanned Collagen: A Molecular Level Study

UV and heat resistance are very important qualities for many leather applications especially, automobile upholstery. This study explores the effect of UV irradiation on zirconium tanned collagen. The changes in the physio-chemical characteristics of native collagen upon UV irradiation differ from that of the zirconium tanned collagen. The UV absorption characteristics of crosslinked collagen increases, which is attributed to the formation of photoproducts on UV radiation. Zirconium crosslinking has been found to reduce this formation when the duration of irradiation is less. There is a gradual decrease in the emission maxima of crosslinked collagen on increasing the time of irradiation, which is ascribed to conformational changes of the aromatic amino acids residue (tyrosine). The duration of irradiation plays a critical role in the conformational changes brought about by it. Thus, the crosslinking brought about by zirconium aids in imparting stability to collagen against UV irradiation.ResumenUV y resistencia al calor son cualidades muy importantes para muchas aplicaciones de cuero especialmente, la tapicería de automóviles. Este estudio explora el efecto de la irradiación ultravioleta en colágenos curtidos al circonio. Los cambios en las características físico-químicas de colágeno nativo a la irradiación UV difieren del colágeno curtido al circonio. Las características de absorción UV del colágeno reticulado aumenta, lo que se atribuye a la formación de foto-productos por la irrradiación UV. Se ha encontrado la reticulación con circonio para reducir esta formación cuando la duración de la irradiación es menor. Hay una disminución gradual en la máxima emisión de colágeno reticulado aumentando el tiempo de irradiación, que se atribuye a cambios de configuración de los residuales de aminoácidos aromáticos (tirosina). La duración de la irradiación desempeña un papel fundamental en los cambios producidos por configuración ella. De este modo, la reticulación provocada por circonio ayuda a impartir estabilidad al colágeno en contra de la irradiación ultravioleta

Sex differences in nucleus accumbens transcriptome profiles associated with susceptibility versus resilience to subchronic variable stress

Depression and anxiety disorders are more prevalent in females, but the majority of research in animal models, the first step in finding new treatments, has focused predominantly on males. Here we report that exposure to subchronic variable stress (SCVS) induces depression-associated behaviors in female mice, whereas males are resilient as they do not develop these behavioral abnormalities. In concert with these different behavioral responses, transcriptional analysis of nucleus accumbens (NAc), a major brain reward region, by use of RNA sequencing (RNA-seq) revealed markedly different patterns of stress regulation of gene expression between the sexes. Among the genes displaying sex differences was DNA methyltransferase 3a (Dnmt3a), which shows a greater induction in females after SCVS. Interestingly, Dnmt3a expression levels were increased in the NAc of depressed humans, an effect seen in both males and females. Local overexpression of Dnmt3a in NAc rendered male mice more susceptible to SCVS, whereas Dnmt3a knock-out in this region rendered females more resilient, directly implicating this gene in stress responses. Associated with this enhanced resilience of female mice upon NAc knock-out of Dnmt3a was a partial shift of the NAc female transcriptome toward the male pattern after SCVS. These data indicate that males and females undergo different patterns of transcriptional regulation in response to stress and that a DNA methyltransferase in NAc contributes to sex differences in stress vulnerability

4,9-Dioxa-1,3(1,2)-dibenzena-2(4,5)-1,3-oxazolidinacyclononaphane

The oxazole ring in the title compound, C20H23NO3, adopts an envelope conformation while the 12-membered ring is in a chair conformation. The dihedral angle between the benzene rings is 37.8 (1)°. The crystal structure displays inter­molecular C—H⋯O hydrogen bonding

A Study on Usage Pattern and Issues Faced by Consumers using Online Grocery Shopping

The fastest-growing segment of the Indian retail market is e-retailing. E-commerce has been a benefit for customers throughout the pandemic. This study assists in identifying the problems that consumers encounter when shopping for groceries online at hypermarkets. It also analyses the consumer's usage patterns when it comes to online grocery shopping. The consumers using the online grocery shopping were contacted for the study. The purposive sampling method was used to identify 120 consumers. Primary data was collected from individual respondents by using a well-structured interview schedule. Simple percentage analysis, Garrett ranking techniques were used to analyses this study objective. The result findings from this study are, Trust on online retailors was the major issue faced by consumer while using online grocery shopping with Garrett score of (70.57). Nearly 39 per cent of consumers frequency of shopping using online grocery shopping was slightly frequently. And 38.3 per cent of consumer spending 5 to 10 hours for using online grocery shopping per month

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics