Have Australian rainfall and cloudiness increased due to the remote effects of Asian anthropogenic aerosols?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94749/1/jgrd13340.pd

The Role of the Multiple Banded Antigen of Ureaplasma parvum in Intra-Amniotic Infection: Major Virulence Factor or Decoy?

The multiple banded antigen (MBA) is a predicted virulence factor of Ureaplasma species. Antigenic variation of the MBA is a potential mechanism by which ureaplasmas avoid immune recognition and cause chronic infections of the upper genital tract of pregnant women. We tested whether the MBA is involved in the pathogenesis of intra-amniotic infection and chorioamnionitis by injecting virulent or avirulent-derived ureaplasma clones (expressing single MBA variants) into the amniotic fluid of pregnant sheep. At 55 days of gestation pregnant ewes (n = 20) received intra-amniotic injections of virulent-derived or avirulent-derived U. parvum serovar 6 strains (2×104 CFU), or 10B medium (n = 5). Amniotic fluid was collected every two weeks post-infection and fetal tissues were collected at the time of surgical delivery of the fetus (140 days of gestation). Whilst chronic colonisation was established in the amniotic fluid of animals infected with avirulent-derived and virulent-derived ureaplasmas, the severity of chorioamnionitis and fetal inflammation was not different between these groups (p>0.05). MBA size variants (32–170 kDa) were generated in vivo in amniotic fluid samples from both the avirulent and virulent groups, whereas in vitro antibody selection experiments led to the emergence of MBA-negative escape variants in both strains. Anti-ureaplasma IgG antibodies were detected in the maternal serum of animals from the avirulent (40%) and virulent (55%) groups, and these antibodies correlated with increased IL-1β, IL-6 and IL-8 expression in chorioamnion tissue (p<0.05). We demonstrate that ureaplasmas are capable of MBA phase variation in vitro; however, ureaplasmas undergo MBA size variation in vivo, to potentially prevent eradication by the immune response. Size variation of the MBA did not correlate with the severity of chorioamnionitis. Nonetheless, the correlation between a maternal humoral response and the expression of chorioamnion cytokines is a novel finding. This host response may be important in the pathogenesis of inflammation-mediated adverse pregnancy outcomes

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

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

Lnc-EPB41-Protein Interactions Associated with Congenital Pouch Colon

Congenital Pouch Colon (CPC) is a rare anorectal anomaly common to northwestern India, specifically Rajasthan. Despite efforts to understand the clinical genetic makeup of CPC, no attempt on identifying non-coding RNAs was done. We have earlier reported CPC&rsquo;s rare variants from whole exome sequencing (WES) across 18 affected samples in a total of 64 subjects. A Smith&ndash;Waterman algorithm was used to infer a couple of lncRNAs from WES samples of CPC with predictions from the Noncode database. Further screening and quantification using polymerase chain reaction (PCR), we ascertained interactions using Micro Scale Thermophoresis (MST). We report the role of lnc-EPB41-1-1 shown to be promiscuously interacting with KIF13A substantiating their role in regulation

Inflammatory mediators weaken the amniotic membrane barrier through disruption of tight junctions

In chorioamnionitis, intra-amniotic infections render the amniotic fluid an adverse environment for the fetus and increase the risk of fetal mortality and morbidity. It remains unclear how infection crosses the amniotic barrier, which is made up of tight junctions (TJs). In this study, we investigated whether amniotic TJs are disrupted in inflammatory conditions such as chorioamnionitis. Amniotic TJs were disrupted by single applications of interleukin (IL)-1β, IL-6, tumour necrosis factor-α(TNF-α), and prostaglandin E2. In organ-cultured amniotic membranes, these inflammatory mediators decreased the claudin-3 and claudin-4 levels at the apical junction at different times. Injecting IL-6 into the amniotic cavity concurrently induced the disruption of amniotic TJs by decreasing the claudin-3 and claudin-4 levels at the apical junction, and the dysfunction of the amniotic barrier; in contrast, injecting TNF-α weakened the amniotic barrier by inducing apoptosis of the amniotic epithelial cells, with no decrease in claudin-3 and claudin-4 at the apical junction. Furthermore, inflammation in the amniotic membrane, which was induced by the administration of lipopolysaccharide to pregnant mice, concurrently caused dysfunction of the amniotic barrier and disruption of TJs, involving the decrease of claudin-3 and claudin-4 levels at the apical junction and apoptosis in the amniotic epithelium. These results indicate that the adverse effects of the inflammatory mediators on amniotic TJs cause severe dysfunction of the amniotic barrier

The role of 99mtechnetium-labelled hepato imino diacetic acid (HIDA) scan in the management of biliary pain

Objective. To assess the outcome of laparoscopic cholecystectomy on the basis of an abnormal provocative 99mtechnetium-labelled hepato imino diacetic acid (HIDA) scan for patients with typical biliary pain and normal trans-abdominal ultrasound (TUS) scan. Patients and methods. Prospective data were collected for 1201 consecutive patients with typical biliary symptoms. Patients who were found to have a normal TUS and upper GI endoscopy subsequently underwent cholescintigraphy (HIDA scan). Patients with an abnormal HIDA scan, i.e.<40% ejection fraction with Sincalide® (cholecystokinin octapeptide) – were offered cholecystectomy. Symptoms and histology were reviewed postoperatively. Results. In all, 48/1201 (4%) patients with typical biliary symptoms had a normal ultrasound and endoscopy; 35/48 patients had an abnormal provocative HIDA scan and all underwent laparoscopic cholecystectomy. Histology in all cases revealed chronic cholecystitis and 18 patients had sludge or microlithiasis within the gallbladder. At 6-week follow-up, 31 of the 35 patients were completely asymptomatic or improved. Furthermore, 79% of patients remained symptom-free or improved at a median follow-up of 28.5 months (range 4–70). Conclusions. HIDA scan is a useful clinical tool as an adjunct to the diagnosis and management of patients who present with typical biliary pain and a normal TUS scan

Observed links between coastal ocean processes and Indian Oil Sardine (Sardinella longiceps) fishery along the southwest coast of India

The annual fishery of the Indian Oil Sardine (IOS), Sardinella longiceps, seems to be influenced by the ambient conditions prevailing in the habitats during their early life-history. The present study is aimed at understanding the putative behaviour of IOS along the southwest coast of India (SWCI) to monsoonal upwelling which triggers surface productivity. Mixed layer temperature is observed to be an indicator of the habitat choice and reproductive performance of IOS. A Multi-Criteria Analysis (MCA) model was envisioned to explain the interannual variability of the IOS fishery. In this model, the coactions of variables such as standardized catch per unit effort (SCPUE) of IOS in the first quarter (January to March), southwest monsoonal upwelling index (SWM-UI), and pre-monsoonal mixed layer temperature (PM-MLT) over three decades from 1985 to 2016 were looked upon as indicators to explain the inter-annual fluctuations in the fishery. Eight different criteria for eight ranks were assigned using reference values for variables. The model ranks the years based on the respective conditions defined based on the suitability criteria for IOS. The model showed a strong relationship of the variables on the annual IOS fishery and revealed that the higher first quarter SCPUE (¿3.678) and SWM-UI (¿758.7 kg/m/s influences the inter-annual variability of the fishery significantly. The primary causative factor for the collapse of this fishery during 1992-99 was the frequent occurrence or co-occurrence of extreme climatic events such as El Niño, La Niña and Indian Ocean Dipole (IOD). Further, a significant increase () in IOS fishery was observed during 2000-07 due to favourable upwelling conditions along the SWCI. The uncertainties prevailing in a complex tropical ecosystem and associated challenges in resolving a multi-craft-gear fishery were addressed using statistical tools to infer logical explanation on the decline and revival of IOS