Production of Bioactive Volatiles by Different Burkholderia ambifaria Strains

Increasing evidence indicates that volatile compounds emitted by bacteria can influence the growth of other organisms. In this study, the volatiles produced by three different strains of Burkholderia ambifaria were analysed and their effects on the growth of plants and fungi, as well as on the antibiotic resistance of target bacteria, were assessed. Burkholderia ambifaria emitted highly bioactive volatiles independently of the strain origin (clinical environment, rhizosphere of pea, roots of maize). These volatile blends induced significant biomass increase in the model plant Arabidopsis thaliana as well as growth inhibition of two phytopathogenic fungi (Rhizoctonia solani and Alternaria alternata). In Escherichia coli exposed to the volatiles of B. ambifaria, resistance to the aminoglycoside antibiotics gentamicin and kanamycin was found to be increased. The volatile blends of the three strains were similar, and dimethyl disulfide was the most abundant compound. Sulfur compounds, ketones, and aromatic compounds were major groups in all three volatile profiles. When applied as pure substance, dimethyl disulfide led to increased plant biomass, as did acetophenone and 3-hexanone. Significant fungal growth reduction was observed with high concentrations of dimethyl di- and trisulfide, 4-octanone, S-methyl methanethiosulphonate, 1-phenylpropan-1-one, and 2-undecanone, while dimethyl trisulfide, 1-methylthio-3-pentanone, and o-aminoacetophenone increased resistance of E. coli to aminoglycosides. Comparison of the volatile profile produced by an engineered mutant impaired in quorum-sensing (QS) signalling with the corresponding wild-type led to the conclusion that QS is not involved in the regulation of volatile production in B. ambifaria LMG strain 1918

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Measurement of Sitting Time in Older Adults With and Without Alzheimer’s Disease

Time spent being sedentary is associated with poorer cognitive function and risk of developing Alzheimer’s disease (AD). The present study aimed to compare patterns of sitting in a free-living environment among older adults with and without early stage AD who were similar in physical limitations, body mass, and cardiorespiratory capacity. We also compared estimates of sitting patterns between two different monitors (postural and non-postural) with different body placements (thigh-worn vs. hip-worn). Comparing older adults without cognitive impairment to those with early AD, we found that although there was no difference in the total amount of daily sitting time (p = .52), the AD group tended to have longer durations of sitting than those without AD. Inclinometry data from the hip-worn ActiGraph GT3X+ consistently underestimated time spent sitting compared to the thigh worn monitor activPAL™ (hours per day, proportion of waking hours, number of sitting bouts greater than 30 minutes, and duration of sitting bouts). Our results have implications for prevention strategies to reduce sedentary time, which is predominantly sitting, in persons with cognitive impairment and highlight the importance of monitor selection and placement for the accurate assessment of sitting patterns in this population

Phases of infection and gene expression of fusarium graminearum during crown rot disease of wheat

Fusarium graminearum causes head blight (FHB) and crown rot (CR) diseases in wheat. Compared with FHB, CR symptom development occurs slowly, usually taking 4 to 8 weeks to become visible. To characterize CR development, we used histological and real-time quantitative polymerase chain reaction analyses to assess fungal colonization during a timecourse of infection

Contact With Nature as a Mental Health Buffer for Lower Income Communities During the COVID-19 Pandemic

Despite a growing number of research outputs on the importance of nature contact during the COVID-19 pandemic, we know of no longitudinal research conducted prior to and during the pandemic among low-income and minority ethnicity populations, i.e., those that might be most affected. Furthermore, we have scant information about how and to what degree contact with nature might protect mental health or mitigate worsening of mental health during the pandemic. We filled these gaps using a subset of a longitudinal study of n = 86 individuals in low-income, predominantly African American, neighborhoods in Detroit, MI, USA. The study addressed the following research questions: (1) did self-reported use and perceived value of nature change during, vs. prior to, the pandemic; (2) did perceived access to outdoor spaces buffer people against mental health issues such as stress, anxiety and depression symptoms; or (3) did objectively measured quality of nature views from home buffer people against mental health issues, taking into account relevant covariates and pandemic experiences (e.g., loss of employment, death of a friend/relative)? While attitudes to nature improved slightly from pre- to during the pandemic, we also observed significant decreases in most types of outdoor physical activity and passive enjoyment of nature (e.g., smelling plants/rain). We found a positive association between visibility of greenspace and perceived stress and anxiety, which not only contradicts previous research findings, but was especially surprising given that overall there was a decrease in perceived stress from 2019–2020. We did not detect associations between perceived access/use of nature and mental health. However, higher depressive symptoms were associated with exposure to more COVID-19-related stressors (lost employment, death of friends from COVID-19, etc.). Taken together, our results indicate that COVID-19 may serve to prolong or exacerbate mental health issues, rather than create them, in this population and that low quality greenspace may perhaps limit the ability for nature view to buffer mental health during the pandemic

Pancreatic cancer genomes reveal aberrations in axon guidance pathways genes

Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n5142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis