Hancockwyatt9123

2-34 vs. SM-102 21, range 5.2-6.7, p = 0.0214). HSCR patients demonstrated a markedly increased percentage of NOS (relaxation neurotransmitter) neurons (50, range 22-85 vs. 37, range 16-80, p = 0.0266). None of the histology measures correlated with presence/absence of constipation at 1-2 year follow-up (p = NS). However, smaller ganglion size and higher percentage of NOS neurons correlated with decreased patient-reported quality of life (r = 0.3838, r = - 0.1809). Conclusion 1-2 year follow-up may be insufficient to determine if resection margin histology correlates with outcomes. Patient-reported quality of life surveys, although limited in number, suggest that neurotransmitter imbalance at the resection margin may predict poor outcomes in HSCR patients. This study supports the concept that the ganglionated portion of the remaining colon post-surgery may not sustain normal bowel function.Purpose Biliary atresia (BA) in twins is extremely rare reported in the literature, but twin studies are useful methods of examining the associated factors of a complex disease. The objective of this study was to analyze the characteristics and patterns of biliary atresia in twins from reviewing available articles. Methods PubMed and EMBASE databases were reviewed for related articles using the keywords biliary atresia, twins, monozygotic (MZ), and dizygotic (DZ), including relevant papers in the reference lists. Results This analysis was extracted from 12 articles, with a total of 35 twin pairs included. BA was found in 36 out of 70 twin subjects (51.4%), of which had an even gender split. 97.1% twins were discordant, among 55.9% of which were monozygotic twin sets, indicating that BA may be related to genetic phenotype or penetrance. Isolated BA was the largest group with 27 (75%) affected twins. Only one pair of dizygotic twins (2.9%) demonstrate concordance for BA, and have one affected family member. Conclusion BA was found in nearly half of twin subjects with an even gender split. Isolated BA was the largest group, in which the number of monozygotic twins was similar with dizygotic twins, so the onset of the disease may not associate with the zygosity of twins. Most of twin sets had discordant disease presentation, especially monozygotic twins therein, emphasizing the role of epigenetic factor in the pathogenesis of BA. Future studies should take genetic testing among any twin sets in BA, especially the disease-associated mutations, thus be useful to investigate the etiology of disease.Drug-induced Mood- and Cognition-related adverse events (MCAEs) are often only detected during the clinical trial phases of drug development, or even after marketing, thus posing a major safety concern and a challenge for both pharmaceutical companies and clinicians. To fill some gaps in the understanding and elucidate potential biological mechanisms of action frequently associated with MCAEs, we present a unique workflow linking observational population data with the available knowledge at molecular, cellular, and psychopharmacology levels. It is based on statistical analysis of pharmacovigilance reports and subsequent signaling pathway analyses, followed by evidence-based expert manual curation of the outcomes. Our analysis (a) ranked pharmaceuticals with high occurrence of such adverse events (AEs), based on disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database, and (b) identified 120 associated genes and common pathway nodes possibly underlying MCAEs. Nearly two-thirds of the identified genes were related to immune modulation, which supports the critical involvement of immune cells and their responses in the regulation of the central nervous system function. This finding also means that pharmaceuticals with a negligible central nervous system exposure may induce MCAEs through dysregulation of the peripheral immune system. Knowledge gained through this workflow unravels putative hallmark biological targets and mediators of drug-induced mood and cognitive disorders that need to be further assessed and validated in experimental models. Thereafter, they can be used to substantially improve in silico/in vitro/in vivo tools for predicting these adversities at a preclinical stage.In humans, pathogenic variants in the DHH gene underlie cases of 46,XY gonadal dysgenesis. DHH is part of the Hedgehog family of proteins, which require extensive processing, including self-cleavage of the precursor for efficient signalling. In our work, we have assessed the effect of several human DHH pathogenic variants involved in recessive complete or partial gonadal dysgenesis, on protein processing and sub-cellular localization. We found that a subset of variants was unable to perform self-cleavage, which correlated albeit not perfectly with an altered subcellular localization of the resulting proteins. For the processing-proficient variants, we used structural modelling tools and molecular dynamic (MD) simulations to predict the potential impact of the variants on protein conformation and/or interaction with partners. Our study contributes to a better understanding of the molecular mechanisms involved in DHH dysfunction leading to 46,XY disorders of sex development.Introduction While liquid chromatography coupled to mass spectrometric detection in the selected reaction monitoring detection mode offers the best quantification sensitivity for omics, the number of target analytes is limited, must be predefined and specific methods developed. Data independent acquisition (DIA), including SWATH using quadrupole time of flight or orbitrap mass spectrometers and generic acquisition methods, has emerged as a powerful alternative technique for quantitative and qualitative analyses since it can cover a wide range of analytes without predefinition. Objectives Here we review the current state of DIA, SWATH-MS and highlight novel acquisition strategies for metabolomics and lipidomics and opportunities for data analysis tools. Method Different databases were searched for papers that report developments and applications of DIA and in particular SWATH-MS in metabolomics and lipidomics. Results DIA methods generate digital sample records that can be mined retrospectively as further knowledge is gained and, with standardized acquisition schemes, used in multiple studies.