Social dilemma in the excess use of antimicrobials incurring antimicrobial resistance

The emergence of antimicrobial resistance (AMR) caused by the excess use of antimicrobials has come to be recognized as a global threat to public health. There is a ‘tragedy of the commons’ type social dilemma behind this excess use of antimicrobials, which should be recognized by all stakeholders. To address this global threat, we thus surveyed eight countries/areas to determine whether people recognize this dilemma and showed that although more than half of the population pays little, if any, attention to it, almost 20% recognize this social dilemma, and 15–30% of those have a positive attitude toward solving that dilemma. We suspect that increasing individual awareness of this social dilemma contributes to decreasing the frequency of AMR emergencies

Unique hemoglobin dynamics in female Tibetan highlanders

Background: Tibetan highlanders have adapted to hypoxic environments through the development of unique mechanisms that suppress an increase in hemoglobin (Hb) concentration even in high-altitude areas. Hb concentrations generally decrease with increasing age. However, in the highlands, chronic altitude sickness is known to occur in the elderly population. To investigate how aging in a hypoxic environment affects Hb levels in Tibetan highlanders, we focused on the Mustang people, who live above 3500 m. We tried to clarify the pure relationship between aging and Hb levels in a hypoxic environment.Results: We found that the Hb concentration increased with increasing age in females but not in males. Multivariate analysis showed that age, pulse pressure, the poverty index, and vascular diameter were strongly correlated with the Hb concentration. Conclusions: We found unique Hb dynamics among female Tibetan highlanders. As seen in these Hb dynamics, there may be sex-based differences in the adaptive mechanism in Tibetan highlanders

Inflammatory bowel disease in Tokushima prefecture : A report of questionnaire investigation

To investigate the number of cases and clinical features of inflammatory bowel disease, a questionnaire was sent to 1,271 hospitals or clinics in Tokushima prefecture. A total of 320 cases were collected from 60 institutes for the period from January to December 1997. Eight cases were excluded from this study because of duplicated report (6 cases) and inadequate diagnosis (2 cases). Finally, 312 cases were investigated on their clinical features, treatments, complications, and prognosis. The cases included 195 ulcerative colitis (male 106, female 83, gender unknown 6 cases, age ranged 9-81, mean 39.5± 14.3 (standard deviation (SD) years old), 69 Crohn's disease (male 39, female 24, gender unknown 6 cases, age ranged 17-87, mean 35.1±10.5 (SD) years old), 28 ischemic colitis (male 11, female 17, mean age 65.9±12.6 (SD) years old), 9 intestinal tuberculosis (male 1, female 6, gender unknown 2, age 66.9±6.1 (SD) years old), 4 intestinal Behcet (male 3, female 1, age 39.0±14.2 (SD) years old), 6 simple ulcers (male 3, female 3, age 67.7±11.8 (SD) years old), and a case of aphtous enteritis. Two toxic megacolon cases and 5 colorectal cancer cases were reported among the 195 ulcerative colitis patients. 44 cases out of 69 Crohn's disease patients were received surgical treatment because of severe complications including perforation (12 cases), stenosis (10 cases), internal fistula formation (8 cases) and so on. However, no case died because of the diseases except 3 untraceable patients

Song Practice Promotes Acute Vocal Variability at a Key Stage of Sensorimotor Learning

BACKGROUND: Trial by trial variability during motor learning is a feature encoded by the basal ganglia of both humans and songbirds, and is important for reinforcement of optimal motor patterns, including those that produce speech and birdsong. Given the many parallels between these behaviors, songbirds provide a useful model to investigate neural mechanisms underlying vocal learning. In juvenile and adult male zebra finches, endogenous levels of FoxP2, a molecule critical for language, decrease two hours after morning song onset within area X, part of the basal ganglia-forebrain pathway dedicated to song. In juveniles, experimental 'knockdown' of area X FoxP2 results in abnormally variable song in adulthood. These findings motivated our hypothesis that low FoxP2 levels increase vocal variability, enabling vocal motor exploration in normal birds. METHODOLOGY/PRINCIPAL FINDINGS: After two hours in either singing or non-singing conditions (previously shown to produce differential area X FoxP2 levels), phonological and sequential features of the subsequent songs were compared across conditions in the same bird. In line with our prediction, analysis of songs sung by 75 day (75d) birds revealed that syllable structure was more variable and sequence stereotypy was reduced following two hours of continuous practice compared to these features following two hours of non-singing. Similar trends in song were observed in these birds at 65d, despite higher overall within-condition variability at this age. CONCLUSIONS/SIGNIFICANCE: Together with previous work, these findings point to the importance of behaviorally-driven acute periods during song learning that allow for both refinement and reinforcement of motor patterns. Future work is aimed at testing the observation that not only does vocal practice influence expression of molecular networks, but that these networks then influence subsequent variability in these skills

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target