Remote ischaemic conditioning: defining critical criteria for success-report from the 11th Hatter Cardiovascular Workshop.

The Hatter Cardiovascular Institute biennial workshop, originally scheduled for April 2020 but postponed for 2 years due to the Covid pandemic, was organised to debate and discuss the future of Remote Ischaemic Conditioning (RIC). This evolved from the large multicentre CONDI-2-ERIC-PPCI outcome study which demonstrated no additional benefit when using RIC in the setting of ST-elevation myocardial infarction (STEMI). The workshop discussed how conditioning has led to a significant and fundamental understanding of the mechanisms preventing cell death following ischaemia and reperfusion, and the key target cyto-protective pathways recruited by protective interventions, such as RIC. However, the obvious need to translate this protection to the clinical setting has not materialised largely due to the disconnect between preclinical and clinical studies. Discussion points included how to adapt preclinical animal studies to mirror the patient presenting with an acute myocardial infarction, as well as how to refine patient selection in clinical studies to account for co-morbidities and ongoing therapy. These latter scenarios can modify cytoprotective signalling and need to be taken into account to allow for a more robust outcome when powered appropriately. The workshop also discussed the potential for RIC in other disease settings including ischaemic stroke, cardio-oncology and COVID-19. The workshop, therefore, put forward specific classifications which could help identify so-called responders vs. non-responders in both the preclinical and clinical settings.

Association between overcrowded households, multigenerational households, and COVID-19: a cohort study.

OBJECTIVES: The role of overcrowded and multigenerational households as a risk factor for COVID-19 remains unmeasured. The objective of this study is to examine and quantify the association between overcrowded and multigenerational households and COVID-19 in New York City (NYC). STUDY DESIGN: Cohort study. METHODS: We conducted a Bayesian ecological time series analysis at the ZIP Code Tabulation Area (ZCTA) level in NYC to assess whether ZCTAs with higher proportions of overcrowded (defined as the proportion of the estimated number of housing units with more than one occupant per room) and multigenerational households (defined as the estimated percentage of residences occupied by a grandparent and a grandchild less than 18 years of age) were independently associated with higher suspected COVID-19 case rates (from NYC Department of Health Syndromic Surveillance data for March 1 to 30, 2020). Our main measure was an adjusted incidence rate ratio (IRR) of suspected COVID-19 cases per 10,000 population. Our final model controlled for ZCTA-level sociodemographic factors (median income, poverty status, White race, essential workers), the prevalence of clinical conditions related to COVID-19 severity (obesity, hypertension, coronary heart disease, diabetes, asthma, smoking status, and chronic obstructive pulmonary disease), and spatial clustering. RESULTS: 39,923 suspected COVID-19 cases were presented to emergency departments across 173 ZCTAs in NYC. Adjusted COVID-19 case rates increased by 67% (IRR 1.67, 95% CI = 1.12, 2.52) in ZCTAs in quartile four (versus one) for percent overcrowdedness and increased by 77% (IRR 1.77, 95% CI = 1.11, 2.79) in quartile four (versus one) for percent living in multigenerational housing. Interaction between both exposures was not significant (ßinteraction = 0.99, 95% CI: 0.99-1.00). CONCLUSIONS: Overcrowdedness and multigenerational housing are independent risk factors for suspected COVID-19. In the early phase of the surge in COVID cases, social distancing measures that increase house-bound populations may inadvertently but temporarily increase SARS-CoV-2 transmission risk and COVID-19 disease in these populations.

Association of ischemic electrocardiographic changes in high-altitude areas with coronary angiography.

BACKGROUND: Soldiers native to lowlands, while sojourning at high altitude (HA), are referred to tertiary care centers with electrocardiographic (ECG) abnormalities. Exposure to HA may precipitate myocardial ischemia in subjects with underlying coronary artery disease (CAD). Conversely, it may produce physiological ECG changes mimicking those of CAD, causing a diagnostic dilemma. This study sought to correlate the presence of CAD on coronary angiography (CAG) with a putative diagnosis of CAD based on clinical findings and ECG. METHODS: A prospective study was conducted on patient's from HA areas, referred for evaluation for CAD to a single center at near-sea-level. Thirty-five minimally symptomatic/asymptomatic soldiers with ECG changes suggestive of CAD, underwent CAG. Correlation was sought between ECG and CAG evidence of CAD. RESULTS: The association of CAD on CAG with clinical and ECG diagnosis of CAD was not significant, 4 of the 35 soldiers (11.4%) showing CAG evidence of CAD (chi square 3.849, p = 0.697). The association between symptoms and coronary artery lesions was, also, not significant, only four of twenty-three (17.4%) minimally symptomatic subjects having CAD on CAG. CONCLUSION: Insignificant numbers of previously healthy persons, who present with minimal symptoms and ECG changes suggestive of CAD while sojourning at HA, have coronary artery involvement on CAG. Those with incidental ECG changes, without symptomatology, do not have CAD on CAG.

Novel identification of Factor XI deficiency in Indian Sahiwal (Bos indicus) cattle.

Factor-XI deficiency (FXID) is inherited as autosomal lethal recessive disorder of carrier Holstein-Friesian bulls. A 76 base pair segment insertion into exon 12 in Factor-XI gene causes FXID in cattle. Keeping this in view the present study was conducted to screen breeding bulls of both indigenous and exotic breeds for mutation in Factor-XI gene and to find out the frequency of FXID carrier animals in breeding bulls. A total of 120 bulls of different age group maintained at Frozen Semen Bull Station, India were randomly selected from different cattle breeds to screen presence of FXID syndrome in breeding sires. Genomic DNA was isolated from blood of the selected bulls. PCR parameters were standardized to obtain 244 and 320 bp amplicons. The results showed that 2 Sahiwal bulls out of 120 animals were carrier for FXID. Amplicons of the carrier animals were sequenced and annoted, which confirms a 76 bp insertion in the exon 12. Bleeding and clotting time showed considerable discrepancy in the carrier animals as compared to the normal animals. The findings of relative mRNA expression of Factor XI transcript revealed identical tendency in the carrier. The frequency of carrier animals and mutant allele was 2.5 % and 0.025 respectively. This study recommends for screening of breeding at AI bull centers in the country for FXID. The study also stands a merit for identification of FXID carrier in Bos indicus for the first time.

The prevalence of abnormal ECG in trained sportsmen.

BACKGROUND: Competitive sports training causes structural and conductive system changes manifesting by various electrocardiographic alterations. We undertook this study to assess the prevalence of abnormal ECG in trained Indian athletes and correlate it with the nature of sports training, that is endurance or strength training. METHODS: We evaluated a standard resting, lying 12 lead Electrocardiogram (ECG) in 66 actively training Indian athletes. Standard diagnostic criteria were used to define various morphological ECG abnormalities. RESULTS: 33/66 (50%) of the athletes were undertaking endurance training while the other 33 (50%) were involved in a strength-training regimen. Overall 54/66 (81%) sportsmen had significant ECG changes. 68% of these changes were considered as normal training related features, while the remaining 32% were considered abnormal. There were seven common training related ECG changes-Sinus Bradycardia (21%), Sinus Arrhythmia (16%), 1st degree Atrioventricular Heart Block (6%), Type 1 2nd-degree Atrioventicular Heart Block (3%), Incomplete Right bundle branch block (RBBB) (24%), Early Repolarization (42%), Left Ventricular Hypertrophy (LVH) (14%); while three abnormal ECG changes--T-wave inversion (13%), RBBB(4%), Right ventricular hypertrophy (RVH) with strain (29%) were noted. Early repolarization (commonest change), sinus bradycardia, and incomplete RBBB were the commoner features noticed, with a significantly higher presence in the endurance trained athletes. CONCLUSION: A high proportion of athletes undergoing competitive level sports training are likely to have abnormal ECG recordings. Majority of these are benign, and related to the physiological adaptation to the extreme levels of exertion. These changes are commoner during endurance training (running) than strength training (weightlifting).

Numerical study on influence of cross flow on rewetting of AHWR fuel bundle.

Numerical study on AHWR fuel bundle has been carried out to assess influence of circumferential and cross flow rewetting on the conduction heat transfer. The AHWR fuel bundle quenching under accident condition is designed primarily with radial jets at several axial locations. A 3D (r, θ, z) transient conduction fuel pin model has been developed to carry out the study with a finite difference method (FDM) technique with alternating direction implicit (ADI) scheme. The single pin has been considered to study effect of circumferential conduction and multipins have been considered to study the influence of cross flow. Both analyses are carried out with the same fluid temperature and heat transfer coefficients as boundary conditions. It has been found from the analyses that, for radial jet, the circumferential conduction is significant and due to influence of overall cross flow the reductions in fuel temperature in the same quench plane in different rings are different with same initial surface temperature. Influence of cross flow on rewetting is found to be very significant. Outer fuel pins rewetting time is higher than inner.

Genome-wide mining of diversity and evolutionary signatures revealed selective hotspots in Indian Sahiwal cattle.

The Sahiwal cattle breed is the best indigenous dairy cattle breed, and it plays a pivotal role in the Indian dairy industry. This is due to its exceptional milk-producing potential, adaptability to local tropical conditions, and its resilience to ticks and diseases. The study aimed to identify selective sweeps and estimate intrapopulation genetic diversity parameters in Sahiwal cattle using ddRAD sequencing-based genotyping data from 82 individuals. After applying filtering criteria, 78,193 high-quality SNPs remained for further analysis. The population exhibited an average minor allele frequency of 0.221 ± 0.119. Genetic diversity metrics, including observed (0.597 ± 0.196) and expected heterozygosity (0.433 ± 0.096), nucleotide diversity (0.327 ± 0.114), the proportion of polymorphic SNPs (0.726), and allelic richness (1.323 ± 0.134), indicated ample genomic diversity within the breed. Furthermore, an effective population size of 74 was observed in the most recent generation. The overall mean linkage disequilibrium (r2) for pairwise SNPs was 0.269 ± 0.057. Moreover, a greater proportion of short Runs of Homozygosity (ROH) segments were observed suggesting that there may be low levels of recent inbreeding in this population. The genomic inbreeding coefficients, computed using different inbreeding estimates (FHOM, FUNI, FROH, and FGROM), ranged from -0.0289 to 0.0725. Subsequently, we found 146 regions undergoing selective sweeps using five distinct statistical tests: Tajima's D, CLR, |iHS|, |iHH12|, and ROH. These regions, located in non-overlapping 500 kb windows, were mapped and revealed various protein-coding genes associated with enhanced immune systems and disease resistance (IFNL3, IRF8, BLK), as well as production traits (NRXN1, PLCE1, GHR). Notably, we identified interleukin 2 (IL2) on Chr17: 35217075-35223276 as a gene linked to tick resistance and uncovered a cluster of genes (HSPA8, UBASH3B, ADAMTS18, CRTAM) associated with heat stress. These findings indicate the evolutionary impact of natural and artificial selection on the environmental adaptation of the Sahiwal cattle population.

Spinigerin induces apoptotic like cell death in a caspase independent manner in Leishmania donovani.

Antimicrobial peptides (AMPs) are multifunctional components of the innate immune system. Chemotherapeutic agents used for treatment of visceral leishmaniasis (VL) are now threatened due to the emergence of acquired drug resistance and toxicity. AMPs are attractive alternative to conventional pharmaceuticals. In this study, first time we explored the antileishmanial activity of spinigerin originally derived from Pseudacanthotermes spiniger. Leishmania donovani promastigotes present apoptosis-like cell death upon exposure to spinigerin (IC50, 150 µM). The infection rate was reduced by 20% upon exposure to 150 µM spinigerin but no cytotoxicity on host macrophages was observed. Elevation of intracellular ROS level and down-regulation of two ROS detoxifying enzymes, ascorbate peroxidase (APx) and trypanothione reductase (TR) suggested essential role of ROS machinery during spinigerin mediated cell death. About 97% cell population was found to be Annexin-V positive; 44% cells being highly Annexin-V positive. Moreover, we observed morphological changes like cell rounding, nuclear condensation, oligonucleosomal DNA degradation and TUNEL positive cells without loss of membrane integrity upon spinigerin exposure, suggests apoptosis-like death. Interestingly, collapse in mitochondrial membrane potential and increased level of intracellular ROS and calcium were not associated with caspase like activity. Computational analysis suggests spiningerin interacts with trypanothione reductase and thus probably interferes its function to detoxify the toxic ROS level. Therefore, spinigerin induces apoptosis-like cell death in L. donovani in a caspase-independent manner. The study elucidates the antileishmanial property of spinigerin that may be considered for future chemotherapeutic option alone or adjunct with other drug regimens for improved treatment of visceral leishmaniasis.

Polyacrylonitrile support impregnated with amine-functionalized graphitic carbon nitride/magnetite composite nanofibers towards enhanced arsenic remediation: A mechanistic approach.

Recently, novel composite materials are rapidly being explored for water treatment applications. However, their physicochemical behavior and mechanistic investigations are still a mystery. Therefore, our key prospect is to develop a highly stable mixed-matrix adsorbent system using polyacrylonitrile (PAN) support impregnated with amine-functionalized graphitic carbon nitride/magnetite (gCN-NH2/Fe3O4) composite nanofibers (PAN/gCN-NH2/Fe3O4: PCNFe) by simple electrospinning techniques. Various instrumental techniques were used to explore the structural, physicochemical, and mechanical behavior of the synthesized nanofiber. The developed PCNFe with a specific surface area of 39.0 m2/g was found to be non-aggregated and to have outstanding water dispersibility, abundant surface functionality, greater hydrophilicity, superior magnetic property, and higher thermal & mechanical characteristics making it favorable for rapid As removal. Based on the experimental findings from the batch study, 97.0 and 99.0 % of arsenite (As(III)) and arsenate (As(V)), respectively, could be adsorbed by utilizing0.02 g of adsorbent dosage within 60 min of contact time at pH 7 and 4, with an initial concentration of 10 mg/L. Adsorption of As(III) and As(V) followed the pseudo-second-order kinetic and Langmuir isotherm models with an sorption capacities of 32.26 and 33.22 mg/g, respectively, at ambient temperature. The adsorption was endothermic and spontaneous, in accordance with the thermodynamic study. Furthermore, the addition of co-anions in a competitive environment did not affect As adsorption except for PO43-. Moreover, PCNFe preserves its adsorption efficiency above 80 % after five regeneration cycles. The combined results of FTIR and XPS after adsorption further support the adsorption mechanism. Also, the composite nanostructures retain their morphological and structural integrity after the adsorption process. The facile synthesis protocol, high As adsorption capacity, and enhanced mechanical integrity of PCNFe foreshadow its huge prospects for real wastewater treatment.

Stable isotope labeling as a promising tool for rapid drug susceptibility testing in Neisseria gonorrhoeae.

The world is heading towards an era of intractable and impending untreatable N. gonorrhoeae, thereby underlining the significance of rapid and accurate prediction of drug resistance as an indispensable need of the hour. In the present study, we optimized and evaluated a stable isotope labeling-based approach using the MALDI-TOF MS (Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry) for rapid and reliable detection of ciprofloxacin and azithromycin resistance in N. gonorrhoeae. All the isolates were cultured under three varied condition setups viz. medium supplemented with normal lysine, heavy lysine (isotope), and heavy lysine along with the antibiotics (ciprofloxacin/azithromycin), respectively. After incubation, spectra were acquired using the MALDI-TOF MS which were further screened for unique patterns (media-specific spectra) to differentiate drug-susceptible and resistant isolates. The results of the stable isotope labeling assay were comparable to the results of phenotypic methods used for susceptibility testing.

BNT162b2 COVID-19 Vaccine Induced Immune Thrombocytopenic Purpura.

Immune thrombocytopenic purpura (ITP) has been reported following vaccinations such as MMR as well as after viral infections such as hepatitis C and HIV. Few case reports have been reported of ITP after COVID-19 infections and COVID-19 vaccines. Herein, we present a patient who presented with severe ITP with a platelet count of 0 after receiving the second dose of the BNT162b2 mRNA COVID-19 vaccine (also known as the Pfizer BioNTech). She subsequently recovered with a prolonged treatment course.

Anaerobic capacity of physically active eumenorrheic females at mid-luteal and mid-follicular phases of ovarian cycle.

AIM: The present study was undertaken to evaluate the anaerobic capacity in repeated sprint cycling bouts during mid-luteal (ML) and mid-follicular (MF) phases of ovarian cycle. METHODS: Twelve physically active females aged 22.41±1.68 years, with normal regular menstrual cycle and VO2max of 34.92±4.85 mL·kg-1·min-1 volunteered as subjects in this study. The menstrual phases were verified through daily basal body temperature recording and serum progesterone analysis. Anaerobic capacity was quantified by measuring maximal accumulated oxygen deficit (MAOD). In this study, MAOD was measured following well established method. Initially, the VO2max of the subjects was measured following a graded exercise protocol on a cycle ergometer. On separate days, the subjects performed sub-maximal cycling exercise at 50%, 60%, 70% and 80% of VO2max for 10 minutes. The linear regression determined from the sub-maximal VO2-power relationship was used to estimate the supra-maximal power output at 120% VO2max. The subjects performed repeated sprint cycling for 3 times at 120% of VO2max with 20 minutes rest between consecutive sprints during MF and ML phases. RESULTS: Results indicated there was no significant difference in maximal accumulated oxygen deficit (MAOD) and sprint performance between MF and ML phases in repeated sprint cycling. Serum progesterone was significantly lower in luteal phase after repeated sprints. CONCLUSION: Hence, it is concluded that the anaerobic capacity is unaffected by ovarian phases in women with regular menstrual cycle. Lower serum progesterone after repeated sprints might be due to the repeated anaerobic activity.

Importance of ischaemic time as a predictor of LV systolic function in Indians.

OBJECTIVE: Sucessful reperfusion therapy in AMI improves LV systolic function. Success in thrombolytic therapy is directly related to the ischaemic time. Our aim in the present study was to observe the importance of ischaemic time as a predictor of left ventricular systolic function in patients undergoing PPCI. In addition, the contribution of presentation delay in determining the ischaemic time in the Indian scenario was also observed. MATERIALS & METHODS: The present pilot study was carried out on 48 Indian patients (Male-40) of STEMI (Killip class I & II) undergoing primary PCI in last 2 yrs. Suggestive chest pain, ECG evidence of STEMI coming within 12 hrs were the inclusion criteria. Patients coming after 12 hours without ongoing chest pain, Killip class III & IV, the patients who were thrombolysed outside and the patients with prior PCland/or CABG were excluded from the study. Cardiac echodoppler study was done in every patient during followup at one month.Every patient received pre and peri procedural abciximab infusion and thrombosuction was done in all before deployment of BMS during the transfemoral primary PCI. RESULTS: Data analysis revealed mean age was 57.6 yrs, male preponderance (80%),diabetes (35%),hypertension (61%), Smoking (61%), average total ischaemic time 7.6 +/- 3.78 hours, average presentation delay 6.26 +/- 3.77 hrs, average door to balloon time 60 +/- 14 mins, SVD (69%), LAD involvement(60%). Multivariate regression analysis without considering any other factor showed predicted LV Systolic function one month post PPCI to be 74.08%. Mean LVEF: 58.2%. Most interesting observation is 0.63% reduction of predicted LVEF for each hour increment of ischaemic time. Also LAD occlusion is associated with 4.91% reduction of predicted LVEF compared to other vessel(s) involvement. All the 48 patients who underwent PPCI not only survived but also had good LV Systolic function one month post PPCI. CONCLUSION: Ischaemic time is an important predictor of LV Systolic function even after PPCI. lncrease in ischaemic time by one hour reduces predicted LVEF by 0.63%.Presentation delay is mostly responsible for total ischaemic time in India.

Extraordinary magnetic properties of double perovskite Eu2CoMnO6 wide band gap semiconductor.

Some novel magnetic behaviours in double perovskite Eu2CoMnO6 (ECMO) have been reported. The x-ray photoemission spectroscopy study shows the presence of mixed valence states of transition metal ions. The UV-visible absorption spectroscopic study suggests that the ECMO has a direct wide band gap. A second-order magnetic phase transition as a sudden jump in the magnetization curve has been observed around 124.5 K. The large bifurcation between the zero field cooling and field cooling, suggests existence of strong spin frustration in the system. The inverse DC susceptibility confirms the presence of the Griffiths like phase. Sharp steps in magnetization have been observed in the M-H curve at 2 K, which vanishes on increasing temperature. The AC susceptibility study demonstrates the Hopkinson like effect as well as the presence of volume spin-glass-like behaviour. The temperature dependent Raman spectrum shows the presence of spin-phonon coupling.

Roles of Re-entrant cluster glass state and spin-lattice coupling in magneto-dielectric behavior of giant dielectric double perovskite La1.8Pr0.2CoFeO6.

La based Co-Fe combined double perovskite (La1.8Pr0.2CoFeO6) was synthesized and the dielectric (zero-field and in-field), magnetic, x-ray absorption and Raman spectroscopy measurements have been investigated for La1.8Pr0.2CoFeO6 double perovskite. The existence of re-entrant cluster glass state is observed. The magneto-dielectric (MD) is found in two temperature regions (25-80 K and 125-275 K). It has been demonstrated that the observed MD at low and high temperatures are respectively due to the spin freezing and the spin-lattice coupling. Furthermore, the very large dielectric constant and the low loss suggest that La1.8Pr0.2CoFeO6 is very important from the application point of view.

Anomalous Hall effect in Cu doped Bi2Te3 topological insulator.

The angle resolved photo-emission spectroscopy (ARPES) study and magneto-transport properties of Bi2Cu x Te3-x have been investigated. ARPES study indicates the clear existence of surface states in the as-prepared samples. The estimated bandgap from ARPES is found to be ∼5 meV and 16 meV respectively for x = 0.03 and x = 0.15 samples. Presence of larger Cu concentration (x = 0.15) introduces magnetic ordering. Observed non-linearity in the Hall data is due to the existence of anomalous Hall effect which can be attributed to the 2D transport. The observed magneto-transport features might be related to the surface carriers which is confirmed by ARPES study.

Structure of the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor.

Memapsin 2 (beta-secretase) is a membrane-associated aspartic protease involved in the production of beta-amyloid peptide in Alzheimer's disease and is a major target for drug design. We determined the crystal structure of the protease domain of human memapsin 2 complexed to an eight-residue inhibitor at 1.9 angstrom resolution. The active site of memapsin 2 is more open and less hydrophobic than that of other human aspartic proteases. The subsite locations from S4 to S2' are well defined. A kink of the inhibitor chain at P2' and the change of chain direction of P3' and P4' may be mimicked to provide inhibitor selectivity.