Cardiac magnetic resonance in tropical endomyocardial fibrosis

Background: Endomyocardial fibrosis has varied presentatation and difficult to diagnose. Aim to elucidate the role of Cardiac Magnetic Resonance (CMR) imaging in the evaluation of Endomyocardial Fibrosis (EMF) and to devise diagnostic criteria for the disease.Methods: Retrospective analysis of cases of restrictive cardiomyopathy referred for Magnetic resonance imaging over a period of 5 years. All patients underwent 1.5 T CMR imaging (Magnetom Avanto, Siemens, Germany) with standard cardiomyopathy protocol. Criteria for diagnosis of RCM included normal sized ventricles, normal/reduced systolic function, uni-/bi-atrial enlargement, normal pericardium and absent septal bounce. Cases diagnosed as EMF on CMR were included in this study. Statistical analysis performed using SPSS software.Results: EMF was diagnosed in 20 patients (31%) [12 males; age 39±18 years]. Ten patients had Right Centricular (RV) EMF, 3 had Left Ventricular (LV) EMF, while 7 had bi-ventricular EMF. Oedema indicating ongoing inflammation was seen in 4 (20%) cases. Apical thrombus was seen in 8(40%) cases and was present in 35% cases of RV and 20% cases of LV involvement. Subendocardial delayed enhancement was always present in the involved ventricle. The RV apex was obliterated in 100% of patients with RV EMF, while LV apex was similarly obliterated in 66% cases with LV disease. Mild-moderate pericardial effusion was observed in 8 patients. On the basis of CMR findings, the disease was classified as early necrotic phase in 1, thrombotic necrotic in 4 and late fibrotic phase in 13 and of different stages in ventricles in 2 cases.Conclusions: EMF was the commonest cause of RCM in this series. Major diagnostic criteria of EMF on CMR include subendocardial delayed enhancement and apical obliteration. Oedema and thrombus are variable findings, depending on disease severity

EFFECT OF CYTOKININ ANALOGUES ON CYTOKININ METABOLISM AND STRESS RESPONSIVE GENES UNDER OSMOTIC STRESS IN WHEAT

Osmotic stress induced by conditions like drought, salinity and heat etc. impairs plant growth and development by affecting plant physiological processes. Present study was conducted in laboratory to understand the role cytokinin analogues (TDZ and BAP) in osmotic stress amelioration and their relative efficiency in inducing stress tolerance. Twenty days old wheat seedlings were treated 20% PEG-6000 to induce osmotic stress (-0.491 MPa). Exogenous application of cytokinin analogues enhanced endogenous cytokinin levels by up-regulating expression of IPT (isopentenyl transferase) and down-regulating CKX (cytokinin oxidase) gene expression under osmotic stress. Further, increase in relative water content (30%), membrane stability (15%) and nitrogen assimilation was observed along with delayed leaf senescence in cytokinin treated seedlings under osmotic stress. The current finding suggested that application of TDZ was found to be more effective as compared to BAP even at lower concentrations

Effect of temperature and time delay in centrifugation on stability of select biomarkers of nutrition and non-communicable diseases in blood samples

Introduction: Preanalytical conditions are critical for blood sample integrity and poses challenge in surveys involving biochemical measurements. A cross sectional study was conducted to assess the stability of select biomarkers at conditions that mimic field situations in surveys. Material and methods: Blood from 420 volunteers was exposed to 2 – 8 °C, room temperature (RT), 22 – 30 °C and > 30 °C for 30 min, 6 hours, 12 hours and 24 hours prior to centrifugation. After different exposures, whole blood (N = 35) was used to assess stability of haemoglobin, HbA1c and erythrocyte folate; serum (N = 35) for assessing stability of ferritin, C-reactive protein (CRP), vitamins B12, A and D, zinc, soluble transferrin receptor (sTfR), total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), tryglicerides, albumin, total protein and creatinine; and plasma (N = 35) was used for glucose. The mean % deviation of the analytes was compared with the total change limit (TCL), computed from analytical and intra-individual imprecision. Values that were within the TCL were deemed to be stable. Result: Creatinine (mean % deviation 14.6, TCL 5.9), haemoglobin (16.4%, TCL 4.4) and folate (33.6%, TCL 22.6) were unstable after 12 hours at 22- 30°C, a temperature at which other analytes were stable. Creatinine was unstable even at RT for 12 hours (mean % deviation: 10.4). Albumin, CRP, glucose, cholesterol, LDL, triglycerides, vitamins B12 and A, sTfR and HbA1c were stable at all studied conditions. Conclusion: All analytes other than creatinine, folate and haemoglobin can be reliably estimated in blood samples exposed to 22-30°C for 12 hours in community-based studies

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

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

Cardiac magnetic resonance in tropical endomyocardial fibrosis

Background: Endomyocardial fibrosis has varied presentatation and difficult to diagnose. Aim to elucidate the role of Cardiac Magnetic Resonance (CMR) imaging in the evaluation of Endomyocardial Fibrosis (EMF) and to devise diagnostic criteria for the disease.Methods: Retrospective analysis of cases of restrictive cardiomyopathy referred for Magnetic resonance imaging over a period of 5 years. All patients underwent 1.5 T CMR imaging (Magnetom Avanto, Siemens, Germany) with standard cardiomyopathy protocol. Criteria for diagnosis of RCM included normal sized ventricles, normal/reduced systolic function, uni-/bi-atrial enlargement, normal pericardium and absent septal bounce. Cases diagnosed as EMF on CMR were included in this study. Statistical analysis performed using SPSS software.Results: EMF was diagnosed in 20 patients (31%) [12 males; age 39±18 years]. Ten patients had Right Centricular (RV) EMF, 3 had Left Ventricular (LV) EMF, while 7 had bi-ventricular EMF. Oedema indicating ongoing inflammation was seen in 4 (20%) cases. Apical thrombus was seen in 8(40%) cases and was present in 35% cases of RV and 20% cases of LV involvement. Subendocardial delayed enhancement was always present in the involved ventricle. The RV apex was obliterated in 100% of patients with RV EMF, while LV apex was similarly obliterated in 66% cases with LV disease. Mild-moderate pericardial effusion was observed in 8 patients. On the basis of CMR findings, the disease was classified as early necrotic phase in 1, thrombotic necrotic in 4 and late fibrotic phase in 13 and of different stages in ventricles in 2 cases.Conclusions: EMF was the commonest cause of RCM in this series. Major diagnostic criteria of EMF on CMR include subendocardial delayed enhancement and apical obliteration. Oedema and thrombus are variable findings, depending on disease severity.</jats:p

<i>Mycobacterium tuberculosis</i> transcriptional regulator Rv1019 is upregulated in hypoxia and negatively regulates <i>Rv3230c</i>-<i>Rv3229c</i> operon encoding enzymes in the oleic acid biosynthetic pathway

AbstractThe main obstacle in eradicating tuberculosis is the ability of Mycobacterium tuberculosis to remain dormant in the host, and then to get reactivated even years later under immuno-compromised conditions. Transcriptional regulation in intracellular pathogens plays an important role in adapting to the challenging environment inside the host cells. Previously, we demonstrated that Rv1019, a putative transcriptional regulator of M. tuberculosis H37Rv, is an autorepressor. We showed that, Rv1019 is cotranscribed with Rv1020 (mfd) and Rv1021 (mazG) encoding DNA repair proteins and negatively regulates the expression of these genes. In the present study, we show that Rv1019 also regulates the expression of the genes Rv3230c and Rv3229c (desA3) which form a two-gene operon in M. tuberculosis. Constitutive expression of Rv1019 in M. tuberculosis significantly downregulated the expression of these genes. Employing Wayne’s hypoxia-induced dormancy model of M. tuberculosis, we show that Rv1019 is upregulated (3-fold) under hypoxia. Finally, by reporter assay, using M. smegmatis as a model, we validate that Rv1019 is recruited to the promoter of Rv3230c-Rv3229c during hypoxia and negatively regulates this operon which is involved in the biosynthesis of oleic acid.</jats:p