Plant Host Traits Mediated by Foliar Fungal Symbionts and Secondary Metabolites.

Fungal symbionts living inside plant leaves ("endophytes") can vary from beneficial to parasitic, but the mechanisms by which the fungi affect the plant host phenotype remain poorly understood. Chemical interactions are likely the proximal mechanism of interaction between foliar endophytes and the plant, as individual fungal strains are often exploited for their diverse secondary metabolite production. Here, we go beyond single strains to examine commonalities in how 16 fungal endophytes shift plant phenotypic traits such as growth and physiology, and how those relate to plant metabolomics profiles. We inoculated individual fungi on switchgrass, Panicum virgatum L. This created a limited range of plant growth and physiology (2-370% of fungus-free controls on average), but effects of most fungi overlapped, indicating functional similarities in unstressed conditions. Overall plant metabolomics profiles included almost 2000 metabolites, which were broadly correlated with plant traits across all the fungal treatments. Terpenoid-rich samples were associated with larger, more physiologically active plants and phenolic-rich samples were associated with smaller, less active plants. Only 47 metabolites were enriched in plants inoculated with fungi relative to fungus-free controls, and of these, Lasso regression identified 12 metabolites that explained from 14 to 43% of plant trait variation. Fungal long-chain fatty acids and sterol precursors were positively associated with plant photosynthesis, conductance, and shoot biomass, but negatively associated with survival. The phytohormone gibberellin, in contrast, was negatively associated with plant physiology and biomass. These results can inform ongoing efforts to develop metabolites as crop management tools, either by direct application or via breeding, by identifying how associations with more beneficial components of the microbiome may be affected.

Uterine Dehiscence in the Early Third Trimester: A Report of Two Cases.

As the incidence of cesarean deliveries increases, so do its accompanying complications. Although the incidence of uterine dehiscence in the late second trimester to the early third trimester is rare, it may be a potentially catastrophic complication if uterine rupture occurs. Here, we present two cases of uterine dehiscence at 28 and 29 weeks, which were diagnosed on prenatal ultrasound and confirmed intraoperatively at the time of cesarean delivery. We recommend consideration of earlier screening for preoperative detection of uterine dehiscence to help prevent maternal and neonatal morbidity and mortality.

Probiotic induced synthesis of microbiota polyamine as a nutraceutical for metabolic syndrome and obesity-related type 2 diabetes.

The gut microbiota regulates multiple facets of host metabolism and immunity through the production of signaling metabolites, such as polyamines which are small organic compounds that are essential to host cell growth and lymphocyte activation. Polyamines are most abundant in the intestinal lumen, where their synthesis by the gut microbiota is influenced by microbiome composition and host diet. Disruption of the host gut microbiome in metabolic syndrome and obesity-related type 2 diabetes (obesity/T2D) results in potential dysregulation of polyamine synthesis. A growing body of evidence suggests that restoration of the dysbiotic gut microbiota and polyamine synthesis is effective in ameliorating metabolic syndrome and strengthening the impaired immune responses of obesity/T2D. In this review, we discuss existing studies on gut microbiome determinants of polyamine synthesis, polyamine production in obesity/T2D, and evidence that demonstrates the potential of polyamines as a nutraceutical in obesity/T2D hosts.

United States Medical School Academic Faculty Workforce Diversity, Institutional Characteristics, and Geographical Distributions From 2014-2018.

Purpose Academic healthcare workforce diversity is important in addressing health disparities. Our goal was to evaluate trends and associations in faculty diversity of United States (US) medical schools over a five-year period. Methods We analyzed the Association of American Medical Colleges (AAMC) Faculty Roster data of 151 US medical schools from 2014-2018. Outcome faculty variables were female gender, underrepresented in medicine (UiM), age, and professorial representation. Predictor variables included geographical distributions, and institutional characteristics. Statistical analysis included Jonckheere-Terpstra test, ANOVA, and regression analysis. Results Female faculty increased from 37.6% to 40.4% (p<0.001), senior faculty (age >60 years) from 22.6% to 25.9% (p=0.001) while UiM faculty stayed relatively flat from 9.74% to 10.08% (p=0.773). UiM [adjusted odds ratio (aOR) = 0.39, p=0.015], and female faculty (aOR=0.3, p=0.001) had independently significantly decreased associations with professorial representation, while senior faculty had increased associations (aOR=3.82, p<0.001). Significant independent differences occurred in female, UiM, and professorial faculty distributions within US regions; Hispanic faculty were highest in Southwest (6.57%) and lowest in Midwest region (1.59%), while African-American faculty were highest in Southeast (8.15%) but lowest in the West (3.12%). UiM faculty had significantly independent decreased associations with MD/PhD degree (aOR=0.30, p=0.004) and higher US ranking institutions (aOR=0.45, p=0.009). Conclusions From 2014 to 2018, female faculty increased modestly while the UiM faculty trend remained flat. Female and UiM faculty were less represented at the professor level. UiM faculty were less represented in higher-ranking institutions. Geographic location is associated with faculty diversity.

Modulation of Gut Microbiota Metabolism in Obesity-Related Type 2 Diabetes Reduces Osteomyelitis Severity.

Staphylococcus aureus is an opportunistic pathogen causing osteomyelitis through hematogenous seeding or contamination of implants and open wounds following orthopedic surgeries. The severity of S. aureus-mediated osteomyelitis is enhanced in obesity-related type 2 diabetes (obesity/T2D) due to chronic inflammation impairing both adaptive and innate immunity. Obesity-induced inflammation is linked to gut dysbiosis, with modification of the gut microbiota by high-fiber diets leading to a reduction in the symptoms and complications of obesity/T2D. However, our understanding of the mechanisms by which modifications of the gut microbiota alter host infection responses is limited. To address this gap, we monitored tibial S. aureus infections in obese/T2D mice treated with the inulin-like fructan fiber oligofructose. Treatment with oligofructose significantly decreased S. aureus colonization and lowered proinflammatory signaling postinfection in obese/T2D mice, as observed by decreased circulating inflammatory cytokines (tumor necrosis factor-α [TNF-α]) and chemokines (interferon-γ-induced protein 10 kDa [IP-10], keratinocyte-derived chemokine [KC], monokine induced by interferon-γ [MIG], monocyte chemoattractant protein-1 [MCP-1], and regulated upon activation, normal T cell expressed and presumably secreted [RANTES]), indicating partial reduction in inflammation. Oligofructose markedly shifted diversity in the gut microbiota of obese/T2D mice, with notable increases in the anti-inflammatory bacterium Bifidobacterium pseudolongum. Analysis of the cecum and plasma metabolome suggested that polyamine production was increased, specifically spermine and spermidine. Oral administration of these polyamines to obese/T2D mice resulted in reduced infection severity similar to oligofructose supplementation, suggesting that polyamines can mediate the beneficial effects of fiber on osteomyelitis severity. These results demonstrate the contribution of gut microbiota metabolites to the control of bacterial infections distal to the gut and polyamines as an adjunct therapeutic for osteomyelitis in obesity/T2D. IMPORTANCE Individuals with obesity-related type 2 diabetes (obesity/T2D) are at a five times increased risk for invasive Staphylococcus aureus osteomyelitis (bone infection) following orthopedic surgeries. With increasing antibiotic resistance and limited discoveries of novel antibiotics, it is imperative that we explore other avenues for therapeutics. In this study, we demonstrated that the dietary fiber oligofructose markedly reduced osteomyelitis severity and hyperinflammation following acute prosthetic joint infections in obese/T2D mice. Reduced infection severity was associated with changes in gut microbiota composition and metabolism, as indicated by increased production of natural polyamines in the gut and circulating plasma. This work identifies a novel role for the gut microbiome in mediating control of bacterial infections and polyamines as beneficial metabolites involved in improving the obesity/T2D host response to osteomyelitis. Understanding the impact of polyamines on host immunity and mechanisms behind decreasing susceptibility to severe implant-associated osteomyelitis is crucial to improving treatment strategies for this patient population.

Workplace Stress and Productivity: A Cross-Sectional Study.

INTRODUCTION: The primary purpose of this study was to evaluate the association between workplace stress and productivity among employees from worksites participating in a WorkWell KS Well-Being workshop and assess any differences by sex and race. METHODS: A multi-site, cross-sectional study was conducted to survey employees across four worksites participating in a WorkWell KS Well Being workshop to assess levels of stress and productivity. Stress was measured by the Perceived Stress Scale (PSS) and productivity was measured by the Health and Work Questionnaire (HWQ). Pearson correlations were conducted to measure the association between stress and productivity scores. T-tests evaluated differences in scores by sex and race. RESULTS: Of the 186 participants who completed the survey, most reported being white (94%), female (85%), married (80%), and having a college degree (74%). A significant inverse relationship was observed between the scores for PSS and HWQ, r = -0.35, p < 0.001; as stress increased, productivity appeared to decrease. Another notable inverse relationship was PSS with Work Satisfaction subscale, r =-0.61, p < 0.001. One difference was observed by sex; males scored significantly higher on the HWQ Supervisor Relations subscale compared with females, 8.4 (SD 2.1) vs. 6.9 (SD 2.7), respectively, p = 0.005. CONCLUSIONS: Scores from PSS and the HWQ appeared to be inversely correlated; higher stress scores were associated significantly with lower productivity scores. This negative association was observed for all HWQ subscales, but was especially strong for work satisfaction. This study also suggested that males may have better supervisor relations compared with females, although no differences between sexes were observed by perceived levels of stress.

Hereditary Benign Intraepithelial Dyskeratosis: Report of a Case and Re-examination of the Evidence for Locus Heterogeneity.

BACKGROUND: Hereditary benign intraepithelial dyskeratosis (HBID) is a rare autosomal-dominant disorder of the conjunctiva and oral mucosa first described in and predominantly affecting descendents of Haliwa-Saponi Native Americans. We report a spontaneous case of histopathologically-confirmed HBID affecting an individual not of Native American ancestry. MATERIALS AND METHODS: Report of a case with histopathologic examination of an excised conjunctival specimen as well as molecular and cytogenetic analysis. RESULTS: A Caucasian boy with a history of oral lesions and conjunctival injection from birth developed bilateral corneal opacities at age 5 and underwent penetrating keratoplasty, with recurrence of the corneal opacification shortly after surgery. Examination of a conjunctival biopsy specimen revealed features consistent with HBID. Copy number variant (CNV) analysis revealed a de novo 4q35 duplication that overlapped the duplication previously associated with HBID, although no genes were identified in the common interval. NLRP1 gene sequencing failed to reveal a presumed pathogenic variant. CONCLUSIONS: HBID may develop de novo in individuals who are not of Native American ancestry. The absence of coding regions in a duplicated region of 4q35 common to both the individual that we report and previously associated with HBID raises questions regarding the significance of this CNV in the pathogenesis of HBID.

A comparison study between ketamine and ketamine-promethazine combination for oral sedation in pediatric dental patients.

This study compared the incidence of vomiting and the sedative effectiveness of ketamine to a ketamine-prornethazine combination in pediatric dental patients. Twenty-two patients with American Society of Anesthesiologists' classification I physical status who were between the ages of 21 and 43 months were randomly divided into 2 groups. The control group received 10 mg/kg of ketamine orally, whereas the experimental group received 10 mg/kg of ketamine and 1.1 mg/kg of promethazine orally. Nitrous oxide in oxygen was supplemented between 35 and 50%. Each patient received 1 or 2 quadrants of restoration by one operator. Heart rate, blood pressure, and oxygen saturation were monitored and recorded during the treatment. Crying, alertness, movement, and overall general behavior were rated using the scale by Houpt et al. A dentist-anesthesiologist conducted the vital sign monitoring and behavioral assessment. Ketamine combined with promethazine eliminated the incidence of vomiting. A 2 x 2 chi-square contingency table showed a statistical difference between the 2 groups at P < .05 (control group, 27%; experimental group, 0%). Ketamine alone yielded better sedations than the combined agents as shown by the Mann-Whitney U statistical analysis (P < .05). Ketamine and a ketamine-promethazine combination are effective in the sedation of pediatric dental patients.

Posterior amorphous corneal dystrophy is associated with a deletion of small leucine-rich proteoglycans on chromosome 12.

Posterior amorphous corneal dystrophy (PACD) is a rare, autosomal dominant disorder affecting the cornea and iris. Next-generation sequencing of the previously identified PACD linkage interval on chromosome 12q21.33 failed to yield a pathogenic mutation. However, array-based copy number analysis and qPCR were used to detect a hemizygous deletion in the PACD linkage interval containing 4 genes encoding small leucine-rich proteoglycans (SLRPs): KERA, LUM, DCN, and EPYC. Two other unrelated families with PACD also demonstrated deletion of these SLRPs, which play important roles in collagen fibrillogenesis and matrix assembly. Given that these genes are essential to the maintenance of corneal clarity and the observation that knockout murine models display corneal phenotypic similarities to PACD, we provide convincing evidence that PACD is associated with haploinsufficiency of these SLRPs.