Rationale High-salt diet (HSD) is one of the most important risk factors for hypertension. Intestinal flora has been reported to be associated with high salt-induced hypertension (hSIH). However, the detailed roles of intestinal flora in hSIH pathogenesis have not yet been fully elucidated. Objective To reveal the roles and mechanisms of intestinal flora in hSIH development. Methods and Results The above-mentioned issues were investigated using various techniques including 16S rRNA gene sequencing, untargeted metabolomics, selective bacterial culture and fecal microbiota transplantation (FMT). We found that HSD induced hypertension in Wistar rats. The fecal microbiota of healthy rats could dramatically lower blood pressure (BP) of hypertensive rats, while the fecal microbiota of hSIH rats had opposite effects. The composition, metabolism and interrelationship of intestinal flora in hSIH rats were considerably reshaped, including the increased corticosterone level and reduced Bacteroides and arachidonic acid (AA) levels, which tightly correlated with BP. The serum corticosterone level was also significantly increased in rats with hSIH. Furthermore, the above abnormalities were confirmed in patients with hypertension. The intestinal Bacteroides fragilis (B. fragilis) could inhibit the production of intestinal-derived corticosterone induced by HSD through its metabolite AA. Conclusions hSIH could be transferred by FMT, indicating the pivotal roles of intestinal flora in hSIH development. HSD reduced the levels of B. fragilis and AA in the intestine, which increased intestinal-derived corticosterone production and corticosterone levels in serum and intestine, thereby promoting BP elevation. This study revealed a novel mechanism different from inflammation/immunity by which intestinal flora regulated BP, namely intestinal flora could modulate BP by affecting steroid hormone levels. These findings enriched the understanding of the function of intestinal flora and its effects on hypertension.In children 39°C, acute otitis media, lower respiratory tract infection (LRTI), or extra-pulmonary complications; otherwise, they were classified as mild. We used multivariable log-binomial models to assess whether M-S influenza disease was associated with increased healthcare utilization. Nearly half of the 1,105 influenza positive children were classified as M-S. Children 6-35 months had the highest proportion of M-S disease (35.1%), mostly due to LRTI (63.2%) and fever (44.6%). Children ≥6 months who had M-S disease were associated with a 1.6 to 2.8 times increased likelihood of having had an emergency department or any follow-up outpatient visits. Those who had M-S disease were associated with an increased likelihood of receiving antibiotics, with the highest likelihood in children 6-35 months (RR 9.0, 95% CI 4.1, 19.8). While more studies are needed, an influenza classification system may distinguish children with more clinically significant disease.Aim The purposes of this study were to examine the effect of service learning on changes in college student attitudes toward disability and identify potential factors to improve the quality of service learning using meta-analysis.Method A total of 1984 potential studies were identified through 6 different databases and 14 studies met the necessary criteria for quantitative analysis. Effect sizes were estimated as Hedges' g using random effects, and heterogeneity among effect sizes was assessed with Q and I2 statistics.Results The overall effect size was positive but small (δ = .41, SE = .05, 95% CI [.33, .50], p  less then  0.05). Additionally, the results confirmed that different programs have different levels of impact on the student attitudes toward disability (Q = 25.71, p  less then  0.05, I2 = 45.54). Service-learning programs that were part of a course requirement, on-campus, included a lecture component, and emphasized teacher-centered goals had smaller impacts than programs that were voluntary, off-crd people with disabilities should incorporate strategies specifically designed to target attitude change.Rationale Transposition of the great arteries (TGA) is one of the most severe types of congenital heart diseases (CHD). Understanding the clinical characteristics and pathogenesis of TGA is therefore urgently needed for patient management of this severe disease. However, the clinical characteristics and genetic etiology underlying TGA remain largely unexplored. Objective We sought to systematically examine the clinical characteristics and genetic etiology for isolated nonsyndromic TGA. Methods and Results We recruited 249 TGA patients (66 family trios) and performed whole-exome sequencing. The incidence of patent ductus arteriosus in dextro-TGA (52.7%) and dextrocardia/mesocardia in congenitally corrected TGA (32.8%) were significantly higher than that in other subtypes. A high prevalence of bicuspid pulmonic valve (9.6%) was observed in TGA patients. Similar results were observed in a replication group of TGA (n=132). this website Through a series of bioinformatics filtering steps, we obtained 82 candidate genes harboring potentially damaging de novo, loss of function, compound heterozygous or X-linked recessive variants. Established CHD-causing genes, such as FOXH1, were found among the list of candidate genes. A total of 19 ciliary genes harboring rare potentially damaging variants were also found; for example, DYNC2LI1 with a de novo putatively damaging variant. The enrichment of ciliary genes supports the roles of cilia in the pathogenesis of TGA. In total, 33% of the TGA probands had more than one candidate gene hit by putatively deleterious variants, suggesting that a portion of the TGA cases were probably affected by oligogenic or polygenic inheritance. Conclusions The findings of clinical characteristic analyses have important implications for TGA patient stratification. The results of genetic analyses highlight the pathogenic role of ciliary genes and a complex genetic architecture underlying TGA.RATIONALE cMyBP-C (cardiac myosin-binding protein-C) is a critical regulator of heart contraction, but the mechanisms by which cMyBP-C affects actin and myosin are only partly understood. A primary obstacle is that cMyBP-C localization on thick filaments may be a key factor defining its interactions, but most in vitro studies cannot duplicate the unique spatial arrangement of cMyBP-C within the sarcomere. OBJECTIVE The goal of this study was to validate a novel hybrid genetic/protein engineering approach for rapid manipulation of cMyBP-C in sarcomeres in situ. METHODS AND RESULTS We designed a novel cut and paste approach for removal and replacement of cMyBP-C N'-terminal domains (C0-C7) in detergent-permeabilized cardiomyocytes from gene-edited Spy-C mice. Spy-C mice express a TEVp (tobacco etch virus protease) cleavage site and a SpyTag (st) between cMyBP-C domains C7 and C8. A cut is achieved using TEVp which cleaves cMyBP-C to create a soluble N'-terminal γC0C7 (endogenous [genetically encoded] N'-terminal domains C0 to C7 of cardiac myosin binding protein-C) fragment and an insoluble C'-terminal SpyTag-C8-C10 fragment that remains associated with thick filaments.