Characterization of Actinomycetes and Trichoderma spp. for cellulase production utilizing crude substrates by response surface methodology

Laboratory bench scaling was done and an average of 1.85 fold increase by Response Surface Methodology (RSM) optimization was obtained. It was found that the predicted value (4.96 IU/ml) obtained by RSM is in close accordance with observed activity 5.14 IU/ml. Endoglucanases are mainly induced by CMC while Wheat bran (natural substrate) exoglucanase is more active when induced by avicel and cellulose. Addition of substrate beyond a level caused inhibition of cellulase production. The molecular weight of protein as determined by SDS-PAGE is very similar to molecular weight of cellulase of Trichoderma viride (T. viride) cellulase and Trichoderma reesei (T. reesei) endoglucanase. T. reesei β-glucosidase has high enzymatic activity on CMC substrate when compared with T. viride β-glucosidase. Secondary structure analysed by using Circular Dichroism confirmed that composition of celluase system is very similar to other analysed species. The cellulase was found to be active in pH range of 4.8-5.5; while temperature range varied from 50°C to 70°C. Although the enzymatic activity produced by mutants were lesser than the parent, but in one case mutants of Trichoderma reesei’s BGL has shown higher activity on cellulose

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

Advanced ultrasound screening for temporomandibular joint (TMJ) internal derangement

Purpose. To present an advanced ultrasound (US) technique and propose its use as a screening diagnostic tool for temporomandibular joint (TMJ) internal derangement. Materials and Methods. The technique is based on maintaining the US probe parallel to the articular disc, rather than traditional axial and coronal views, with the position described relative to a clock face. Validation was achieved by direct comparison with magnetic resonance imaging (MRI). A total of 61 patients, with age ranging from 13 to 67 years, were prescreened for TMJ pain and internal derangement, underwent US imaging for screening, and MRI evaluation for final diagnosis. Results. 29 of the 61 patients had disc pathology on MRI. US screening produced no false positive results and only 6 false negative results, corresponding to a sensitivity of 79% and specificity of 100%. Half of the false negative cases involved disc pathology with a medial component to the disc displacement. Conclusion. US is both a sensitive and a specific screening tool for TMJ dysfunction when used by an appropriately trained operator, with the exception of medially displaced discs. If TMJ assessment is found to be abnormal, the patient should be referred for MRI, and any patient scheduled for surgery must have the diagnosis confirmed by MRI. If a component of medial disc displacement is suspected, MRI should be performed despite a normal screening US