Clinico-Epidemiological Profile, Trends, and Health-Related Outcomes of Snakebite Victims: A One-Year Prospective Study from Eastern India.

INTRODUCTION: Snakebite envenomation is a significant life-threatening public health problem in Southeast Asia (SEA). In this region, India reported the largest number of snakebite deaths from 2000 to 2019 (1.2 million), with an average of 58,000 deaths yearly. METHODS: This prospective observational study was carried out among snakebite victims at the emergency department (ED) of a tertiary care public sector hospital in eastern India. RESULTS: A total of 145 cases of venomous snakebite were investigated. More than half (n = 81, 56%) of the snakebite victims were between 17 to 45 years. Most of the snakebite victims were male (68%) and were farmers (53%) by occupation. The majority of snakebites occurred during the daytime (76%) and while outdoors (67%). Most victims sustained a bite on the lower extremity (71%). The peak incidence of snakebites occurred from June to September (69%). Three-quarters of all patients were unaware of the required first aid measures following a snakebite. Among the 145 venomous snakebites, 48 were presumptively identified as the Indian cobra, 32 by the Indian krait, 56 by the Russel's viper, and 9 by saw-scaled viper. The mean duration from the snakebite to the onset of systemic effects in the Indian cobra was 52 ± 14.28 min, 66 ± 18.35 min in the Indian krait, 42 ± 13.47 min in Russel's viper, and 48 ± 16.38 min in saw-scaled viper. Respiratory failure was the commonly observed complication following an elapid envenomation. The mortality rate was 2.1% among the patients treated with antivenom. CONCLUSIONS: Snakebite is considered an occupational hazard in India, commonly affecting the young population in their productive period. The peak incidence was during monsoon season, and the majority had neurotoxic envenomation following an elapid bite (55%) that contributed to the increased mortality and morbidity among young adults. Of the 145 patients, the majority (84%) recovered fully with treatment; 16% of the victims developed morbidity viz cellulitis, respiratory failure, acute renal failure, compartment syndrome, local tissue necrosis, intracerebral hemorrhage, and disseminated intravascular coagulation. Appropriate first aid measures and timely medical intervention can significantly improve the treatment outcome following snakebites.

ADAMTSL2 protein and a soluble biomarker signature identify at-risk non-alcoholic steatohepatitis and fibrosis in adults with NAFLD.

BACKGROUND & AIMS: Identifying fibrosis in non-alcoholic fatty liver disease (NAFLD) is essential to predict liver-related outcomes and guide treatment decisions. A protein-based signature of fibrosis could serve as a valuable, non-invasive diagnostic tool. This study sought to identify circulating proteins associated with fibrosis in NAFLD. METHODS: We used aptamer-based proteomics to measure 4,783 proteins in 2 cohorts (Cohort A and B). Targeted, quantitative assays coupling aptamer-based protein pull down and mass spectrometry (SPMS) validated the profiling results in a bariatric and NAFLD cohort (Cohort C and D, respectively). Generalized linear modeling-logistic regression assessed the ability of candidate proteins to classify fibrosis. RESULTS: From the multiplex profiling, 16 proteins differed significantly by fibrosis in cohorts A (n = 62) and B (n = 98). Quantitative and robust SPMS assays were developed for 8 proteins and validated in Cohorts C (n = 71) and D (n = 84). The A disintegrin and metalloproteinase with thrombospondin motifs like 2 (ADAMTSL2) protein accurately distinguished non-alcoholic fatty liver (NAFL)/non-alcoholic steatohepatitis (NASH) with fibrosis stage 0-1 (F0-1) from at-risk NASH with fibrosis stage 2-4, with AUROCs of 0.83 and 0.86 in Cohorts C and D, respectively, and from NASH with significant fibrosis (F2-3), with AUROCs of 0.80 and 0.83 in Cohorts C and D, respectively. An 8-protein panel distinguished NAFL/NASH F0-1 from at-risk NASH (AUROCs 0.90 and 0.87 in Cohort C and D, respectively) and NASH F2-3 (AUROCs 0.89 and 0.83 in Cohorts C and D, respectively). The 8-protein panel and ADAMTSL2 protein had superior performance to the NAFLD fibrosis score and fibrosis-4 score. CONCLUSION: The ADAMTSL2 protein and an 8-protein soluble biomarker panel are highly associated with at-risk NASH and significant fibrosis; they exhibited superior diagnostic performance compared to standard of care fibrosis scores. LAY SUMMARY: Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of liver disease worldwide. Diagnosing NAFLD and identifying fibrosis (scarring of the liver) currently requires a liver biopsy. Our study identified novel proteins found in the blood which may identify fibrosis without the need for a liver biopsy.

Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases.

The non-receptor protein tyrosine phosphatase SHP2, encoded by PTPN11, has an important role in signal transduction downstream of growth factor receptor signalling and was the first reported oncogenic tyrosine phosphatase. Activating mutations of SHP2 have been associated with developmental pathologies such as Noonan syndrome and are found in multiple cancer types, including leukaemia, lung and breast cancer and neuroblastoma. SHP2 is ubiquitously expressed and regulates cell survival and proliferation primarily through activation of the RAS­ERK signalling pathway. It is also a key mediator of the programmed cell death 1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) immune checkpoint pathways. Reduction of SHP2 activity suppresses tumour cell growth and is a potential target of cancer therapy. Here we report the discovery of a highly potent (IC50 = 0.071 µM), selective and orally bioavailable small-molecule SHP2 inhibitor, SHP099, that stabilizes SHP2 in an auto-inhibited conformation. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism. SHP099 suppresses RAS­ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells in vitro and is efficacious in mouse tumour xenograft models. Together, these data demonstrate that pharmacological inhibition of SHP2 is a valid therapeutic approach for the treatment of cancers.

The perceived social stigma, self-esteem, and its determinants among the health care professionals working in India during COVID 19 pandemic.

BACKGROUND: Health conditions perceived as contagious, dangerous, or incurable are associated with some facets of social stigma. METHODS: A cross-sectional survey was conducted from May 9, 2020 to June 9, 2020, among frontline healthcare workers (HCWs) in India to understand their perceived stigmatizing experiences (SE) and self-esteem during the COVID-19 pandemic. Google forms, an online forms tool, was used to create the survey, and samples were recruited through snowball sampling. Data comprised baseline characteristics of HCWs and their responses to the modified version of the Inventory of Stigmatizing Experiences and the Rosenberg Self-Esteem Scale. RESULTS: Of the 600 participants (mean age: 30.9 ± 6.7 years), 76% comprised of nurses. Most participants were residing in urban areas and working in government sectors in clinical areas. Approximately 66.3% HCWs had at least 1 SE, and 51.7% reported a high impact of stigma (SI) across their various life domains, viz. quality of life, social contacts, self-esteem, and family relations, but 73% had normal self-esteem. The SI was more at the family level than at the individual level. The prevalence of SE (69.5% vs. 56.6%) and psychosocial SI (54.5% vs. 44.1%) was higher among nurses than among doctors. Being a nurse and working in clinical areas were statistically significant (P < 0.05 and < 0.01, respectively) for predicting SE likelihood. CONCLUSION: Although HCWs have their own apprehensions, they do have high self-esteem and continue to deliver professional duties despite their SE. The government should frame guidelines to stop such discrimination and hail the saviors.

Application of Large-Scale Aptamer-Based Proteomic Profiling to Planned Myocardial Infarctions.

BACKGROUND: Emerging proteomic technologies using novel affinity-based reagents allow for efficient multiplexing with high-sample throughput. To identify early biomarkers of myocardial injury, we recently applied an aptamer-based proteomic profiling platform that measures 1129 proteins to samples from patients undergoing septal alcohol ablation for hypertrophic cardiomyopathy, a human model of planned myocardial injury. Here, we examined the scalability of this approach using a markedly expanded platform to study a far broader range of human proteins in the context of myocardial injury. METHODS: We applied a highly multiplexed, expanded proteomic technique that uses single-stranded DNA aptamers to assay 4783 human proteins (4137 distinct human gene targets) to derivation and validation cohorts of planned myocardial injury, individuals with spontaneous myocardial infarction, and at-risk controls. RESULTS: We found 376 target proteins that significantly changed in the blood after planned myocardial injury in a derivation cohort (n=20; P<1.05E-05, 1-way repeated measures analysis of variance, Bonferroni threshold). Two hundred forty-seven of these proteins were validated in an independent planned myocardial injury cohort (n=15; P<1.33E-04, 1-way repeated measures analysis of variance); >90% were directionally consistent and reached nominal significance in the validation cohort. Among the validated proteins that were increased within 1 hour after planned myocardial injury, 29 were also elevated in patients with spontaneous myocardial infarction (n=63; P<6.17E-04). Many of the novel markers identified in our study are intracellular proteins not previously identified in the peripheral circulation or have functional roles relevant to myocardial injury. For example, the cardiac LIM protein, cysteine- and glycine-rich protein 3, is thought to mediate cardiac mechanotransduction and stress responses, whereas the mitochondrial ATP synthase F0 subunit component is a vasoactive peptide on its release from cells. Last, we performed aptamer-affinity enrichment coupled with mass spectrometry to technically verify aptamer specificity for a subset of the new biomarkers. CONCLUSIONS: Our results demonstrate the feasibility of large-scale aptamer multiplexing at a level that has not previously been reported and with sample throughput that greatly exceeds other existing proteomic methods. The expanded aptamer-based proteomic platform provides a unique opportunity for biomarker and pathway discovery after myocardial injury.

Aptamer Proteomics for Biomarker Discovery in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Proteomic Substudy.

BACKGROUND: Prognostic markers and biological pathways linked to detrimental clinical outcomes in heart failure with preserved ejection fraction (HFpEF) remain incompletely defined. METHODS AND RESULTS: We measured serum levels of 4123 unique proteins in 1117 patients with HFpEF enrolled in the PARAGON-HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) trial using a modified aptamer proteomic assay. Baseline circulating protein concentrations significantly associated with the primary end point and the timing and occurrence of total heart failure hospitalization and cardiovascular death were identified by recurrent events regression, accounting for multiple testing, adjusted for age, sex, treatment, and anticoagulant use, and compared with published analyses in 2515 patients with heart failure with reduced ejection fraction from the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and ATMOSPHERE (Efficacy and Safety of Aliskiren and Aliskiren/Enalapril Combination on Morbidity-Mortality in Patients With Chronic Heart Failure) clinical trials. We identified 288 proteins that were robustly associated with the risk of heart failure hospitalization and cardiovascular death in patients with HFpEF. The baseline proteins most strongly related to outcomes included B2M (ß-2 microglobulin), TIMP1 (tissue inhibitor of matrix metalloproteinase 1), SERPINA4 (serpin family A member 4), and SVEP1 (sushi, von Willebrand factor type A, EGF, and pentraxin domain containing 1). Overall, the protein-outcome associations in patients with HFpEF did not markedly differ as compared with patients with heart failure with reduced ejection fraction. A proteomic risk score derived in patients with HFpEF was not superior to a previous proteomic score derived in heart failure with reduced ejection fraction nor to clinical risk factors, NT-proBNP (N-terminal pro-B-type natriuretic peptide), or high-sensitivity cardiac troponin. CONCLUSIONS: Numerous serum proteins linked to metabolic, coagulation, and extracellular matrix regulatory pathways were associated with worse HFpEF prognosis in the PARAGON-HF proteomic substudy. Our results demonstrate substantial similarities among serum proteomic risk markers for heart failure hospitalization and cardiovascular death when comparing clinical trial participants with heart failure across the ejection fraction spectrum. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifiers: NCT01920711, NCT01035255, NCT00853658.

Effectiveness of breathing exercise on the duration of labour: A systematic review and meta-analysis.

Background: Prolonged labour intensifies labour pain, and failure to address labour pain may lead to abnormal labour and augments the usage of operative interventions. Prolonged labour is common among women, resulting in maternal morbidity, increased caesarean section (CS) rates, and postpartum complications. It may bring forth negative birth experiences that may increase the preference for CS. There is a dearth of evidence concerning the effectiveness of breathing exercises on the duration of labor. As per our knowledge, this is the first systematic review and meta-analysis on the effect of breathing exercises on the duration of labor. This systematic review and meta-analysis aimed to appraise the evidence concerning the effectiveness of breathing exercises on the duration of labour. Methods: Electronic databases MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Web of Science, SCOPUS, and ClinicalKey were searched for randomized controlled trials, quasi-experimental studies published in the English language between January 2005 to March 2022 that reported on the effectiveness of breathing exercises on the duration of labour. Duration of labour was the primary analysed outcome. The secondary outcomes assessed were anxiety, duration of pain, APGAR scores, episiotomy, and mode of delivery. Meta-analysis was done using RevMan v5.3. Results: The reviewed trials involved 1418 participants, and the study participants ranged from 70 to 320. The mean gestational weeks of the participants among the reported trials was 38.9 weeks. Breathing exercise shortened the duration of the intervention group's second stage of labour compared with the control group. Conclusions: Breathing exercise is a beneficial preventive intervention in shortening the duration of second stage of labour. Registration: The review protocol was registered with PROSPERO (CRD42021247126).

A proteogenomic view of Parkinson's disease causality and heterogeneity.

The pathogenesis and clinical heterogeneity of Parkinson's disease (PD) have been evaluated from molecular, pathophysiological, and clinical perspectives. High-throughput proteomic analysis of cerebrospinal fluid (CSF) opened new opportunities for scrutinizing this heterogeneity. To date, this is the most comprehensive CSF-based proteomics profiling study in PD with 569 patients (350 idiopathic patients, 65 GBA + mutation carriers and 154 LRRK2 + mutation carriers), 534 controls, and 4135 proteins analyzed. Combining CSF aptamer-based proteomics with genetics we determined protein quantitative trait loci (pQTLs). Analyses of pQTLs together with summary statistics from the largest PD genome wide association study (GWAS) identified 68 potential causal proteins by Mendelian randomization. The top causal protein, GPNMB, was previously reported to be upregulated in the substantia nigra of PD patients. We also compared the CSF proteomes of patients and controls. Proteome differences between GBA + patients and unaffected GBA + controls suggest degeneration of dopaminergic neurons, altered dopamine metabolism and increased brain inflammation. In the LRRK2 + subcohort we found dysregulated lysosomal degradation, altered alpha-synuclein processing, and neurotransmission. Proteome differences between idiopathic patients and controls suggest increased neuroinflammation, mitochondrial dysfunction/oxidative stress, altered iron metabolism and potential neuroprotection mediated by vasoactive substances. Finally, we used proteomic data to stratify idiopathic patients into "endotypes". The identified endotypes show differences in cognitive and motor disease progression based on previously reported protein-based risk scores.Our findings not only contribute to the identification of new therapeutic targets but also to shape personalized medicine in CNS neurodegeneration.

Clinical characteristics of heart failure with reduced ejection fraction patients with rare pathogenic variants in dilated cardiomyopathy-associated genes: A subgroup analysis of the PARADIGM-HF trial.

AIMS: To evaluate the prevalence of pathogenic variants in genes associated with dilated cardiomyopathy (DCM) in a clinical trial population with heart failure and reduced ejection fraction (HFrEF) and describe the baseline characteristics by variant carrier status. METHODS AND RESULTS: This was a post hoc analysis of the Phase 3 PARADIGM-HF trial. Forty-four genes, divided into three tiers, based on definitive, moderate or limited evidence of association with DCM, were assessed for rare predicted loss-of-function (pLoF) variants, which were prioritized using ClinVar annotations, measures of gene transcriptional output and evolutionary constraint, and pLoF confidence predictions. Prevalence was reported for pLoF variant carriers based on DCM-associated gene tiers. Clinical features were compared between carriers and non-carriers. Of the 1412 HFrEF participants with whole-exome sequence data, 68 (4.8%) had at least one pLoF variant in the 8 tier-1 genes (definitive/strong association with DCM), with Titin being most commonly affected. The prevalence increased to 7.5% when considering all 44 genes. Among patients with idiopathic aetiology, 10.0% (23/229) had tier-1 variants only and 12.6% (29/229) had tier-1, -2 or -3 variants. Compared to non-carriers, tier-1 carriers were younger (4 years; adjusted p-value [padj ] = 4 × 10-3 ), leaner (27.8 kg/m2 vs. 29.4 kg/m2 ; padj = 3.2 × 10-3 ), had lower ejection fraction (27.3% vs. 29.8%; padj = 5.8 × 10-3 ), and less likely to have ischaemic aetiology (37.3% vs. 67.4%; padj = 4 × 10-4 ). CONCLUSION: Deleterious pLoF variants in genes with definitive/strong association with DCM were identified in ∼5% of HFrEF patients from a PARADIGM-HF trial subset, who were younger, had lower ejection fraction and were less likely to have had an ischaemic aetiology.

Prevalence of Somatic Symptoms and Quality of Life Among Married Women Having a Distant Relationship With Their Spouses in Mangalore, India.

BACKGROUND: Married women having a distant relationship with their husbands are prone to mental disorders like somatic symptoms, eventually reducing their quality of life (QoL). OBJECTIVE: To assess the somatic symptoms and quality of life among married women having a distant relationship with their spouses. METHODOLOGY: A descriptive cross-sectional study was conducted in 2018. Women having a distant relationship were selected using snowball sampling from selected urban areas of Mangalore, Karnataka. The Scale for Assessment of Somatic Symptoms (SASS) and the World Health Organization Quality of Life Scale (WHOQOL)-BREF questionnaire were used to assess somatic symptoms and quality of life, respectively. Multiple linear regression was used to identify the predictors of somatic symptoms and QoL. RESULTS: Out of 100 married women with a distant relationship, 83% experienced at least one symptom at a moderate/severe level, whereas the prevalence of somatic symptoms was 30% (at least one symptom at a severe level). Among these 30 women, the majority were in the age groups of 25-30 (32%) and 31-35 (30%). The somatic symptoms had a negative association with Christians (p<0.05), whereas they were positively associated with women living in nuclear families (p<0.05) and marriages of less than 3 years (p<0.05). Among the four domains of WHOQOL-BREF, the highest QoL was seen in the social domain (61.06 ± 18.58), the lowest was seen in the psychological domain (54.78 ± 13.05). CONCLUSION: Women who have a distant relationship with their husbands manifest somatic symptoms which decrease their quality of life. This emphasizes the need to use different approaches during hospital visits and community-oriented programs to identify and improve mental health among married women and wellbeing in the family.

Intrapartum respectful maternity care practices and its barriers in Eastern India.

Background: Respectful maternal care (RMC) is increasingly recognized globally as critical to improving the quality of maternity care as women deserve respectful and dignified care. Numerous women face disrespectful maternal care during labor and delivery, especially in low- and middle-income countries, which dissuades them from seeking institutional care. Women, the consumers of care, are better positioned to report on the level of respectful care they receive. Health care workers' perspectives on barriers to delivering respective maternity care are seldom explored. Thus, this study aims to assess the levels of respectful maternity care and its barriers. Methods: This cross-sectional study assesses the level of RMC and its barriers in the labor room of tertiary care hospital in Odisha among 246 women selected by consecutive sampling technique by a questionnaire. Results: More than one-third of women reported good RMC. Although women rated high in domains of environment, resources, dignified care, and non-discrimination, non-consented care and non-confidential care were poorly rated. Barriers that adversely affect the delivery of RMC perceived by health care workers were lack of resources, staffing, uncooperative mother, communication issues, privacy issues, lack of policies, workload, and language problems. There was a significant association of RMC with age, education, occupation, and income. In contrast, residence, marital status, number of children, antenatal visit, type of institute of antenatal care, mode of delivery, and gender of health care provider were not associated with RMC. Conclusion: Given the above findings, we recommend vigorous efforts to improve the institutional policies, resources, training, and supervision of health care professionals on women's rights during childbirth to strengthen the quality of care for positive birth experiences.

Knowledge, perceived threats and protective behaviour related to COVID 19 among pregnant women.

Pregnancy is usually a period of joy, happiness, and expectation for a baby. However, COVID-19 changed the priority and created an environment of worry, perceived threats, and increased protective behaviour to safeguard mother and baby against COVID-19. METHOD: A cross-sectional study was conducted to assess, the level of knowledge, perceived threats, protective behavior, and factors affecting protective behavior among pregnant women by using a convenient sampling technique. The questionnaire collected the demographic profile, knowledge related to the risk factors of COVID-19, perceived treats (severity and susceptibility), and protective behaviors adopted by pregnant women. RESULT: Among the 325 pregnant women, knowledge was high (50.5%), the highest relative Importance Index for perceived susceptibility and severity was coming to hospital visits (0.64), and the belief that COVID-19 is a severe health problem (0.81) respectively. Around 69.8% had followed COVID appropriate protective behaviors. The study also revealed that, a high level of knowledge (AOR=2.45, 95%CI:1.45-4.13) and having a university education (AOR= 2.91, 95%CI:1.62-5.22) had a significantly higher probability of adapting COVID appropriate behavior among pregnant women. CONCLUSION: This study emphasizes the need to streamline communication and adequate education for pregnant women which can help reduce perceived threats and improve protective behavior.

Do different positions during a non-stress test affect the maternofetal physiological parameters and comfort in pregnant women?

BACKGROUND: A non-stress test (NST) is an essential diagnostic test performed during pregnancy to assess fetal well-being. It is a recording of fetal movements besides fetal heart rate, indicating fetal biophysiological well-being. As maternal physiology is altered in various positions, apt positioning during the NST is essential for accurate results while ensuring maternal comfort. This study aims to evaluate the effect of different maternal positions, left lateral and semi-fowler's, on NST reactivity, maternal blood pressure, heart rate, and comfort in pregnant women while performing the NST. MATERIALS AND METHODS: This crossover study evaluated 50 healthy pregnant women between 32 and 40 weeks of gestation with no obstetric complications for the effect of maternal positions on maternofetal physiological parameters and comfort. The NST was performed for 20 min in each position with a washout period of 10 min. The maternofetal physiological parameters were recorded by a calibrated sphygmomanometer and the electrocardiograph interpretations. The maternal comfort was assessed using a maternal comfort rating scale (MCRS) for each position after the NST. Relevant descriptive and inferential statistics are applied to compute the results. RESULTS: Statistically, there was a significant difference in the mean maternal blood pressure and heart rate between the left lateral and semi-fowler's positions at 0 and 20 min (P = 0.001), whereas within the groups, in the same position at 0 and 20 min, no significant difference was found. There was no significant difference in NST reactivity (P = 0.79) in different positions. There was no significant difference between the MCR scores of women in either of the positions (Z = -1.64, df = 49, P = 0.100). CONCLUSION: Semi-fowler's position demonstrated favorable maternal blood pressure and heart rate during the NST in the third trimester of pregnancy, though it was clinically not significant. There was no significant difference in the comfort of women in both positions. Hence, either of the positions can be implemented in practice as an alternative position while performing the NST, based on the women's preference.

Scrutiny of COVID-19 response strategies among severely affected European nations.

Although the health care systems in Europe are considered the global benchmark, European nations were severely affected by the coronavirus disease 2019 (COVID-19) pandemic. This manuscript aimed to examine the strategies implemented to combat the COVID-19 pandemic by France, the United Kingdom, Spain, Italy, Germany, and Russia and their outcomes in terms of the number of cases, testing, and deaths. This is the first review of its kind that extensively analyzes the preparedness, mitigation, and response strategies against the COVID-19 pandemic adopted by these nations. This paper further suggests a strategic preparedness model for future pandemics. From the analysis, we found that a decentralized approach, prompt decision-making and timely execution, coordination between local health authorities, and public participation in the implementation of strategies could substantially reduce the case fatality rate. Nations with a high percentage of gross domestic product invested in the health sector, as well as more nurses, physicians, hospital beds, intensive care unit beds, and ventilators, better managed the pandemic. Instead, nations that postponed their pandemic response by delaying tracking, tracing, testing, quarantine, and lockdown were badly affected. The lessons learned from the present pandemic could be used as a guide to prepare for further pandemics.

Determinants of Willingness for COVID-19 Vaccine: Implications for Enhancing the Proportion of Vaccination Among Indians.

Objective To assess willingness for the coronavirus disease 2019 (COVID-19) vaccine and identify the factors attributing to the willingness. Design A cross-sectional study was conducted, adopting an exponential, non-discriminative snowball sampling technique. The questionnaire collected the socio-demographic profile, history of COVID-19 infection, presence of co-morbidities (diabetes mellitus, hypertension, chronic obstructive pulmonary disease (COPD), asthma, cancer), willingness, and preference of vaccine among participants. An online platform (Google Forms) was used to collect data from all over India. A total of 2032 Indian adults aged above 18 years were included in the study. Results Around 1598 (78.6%) expressed willingness to receive the COVID vaccine, and among the healthcare providers (HCPs), 579 (80.3%) were willing for COVID vaccination. Factors like the belief that the vaccine is necessary (aOR=1.68, 95% CI =1.34 to 2.11), respondents having no history of COVID infection (aOR=0.71, 95% CI: 0.52 to 0.97), having trust in the government (aOR=6.09, CI: 4.59 to 7.98), people who felt the cost of the vaccine didn't matter (aOR=4.92, CI: 3.80 to 6.37), and respondents with no perceived risk of COVID infection (aOR=0.63; CI: 0.47 to 0.83) were more associated with willingness for COVID vaccination. Conclusions An effective vaccine should be well-received by the public. The responsibility lies with the government, health authorities, and manufacturers to take appropriate steps to dispel rumors in order to ensure people's understanding and acceptance.

COVID-19: Weighing the Endeavors of Nations, with Time to Event Analysis.

The cataclysmic COVID-19 pandemic erupted silently causing colossal impact worldwide, the repercussions of which indicated a lackadaisical vigilance in preparation for such a pandemic. This review assessed the measures taken by nations to contain this pandemic. A literature review was conducted using Medline, Google Scholar, Science Direct, Scopus, and WHO website. There were 8 nations (selected from the GHS index list) appraised for containment strategies. This was achieved by using mortality rate (per million) as the primary endpoint. The nations which were proactive, initiated scientific strategies earlier with rigor, appeared to have succeeded in containing the pandemic, although it is still too early to arbitrate a verdict. The so called "pandemic war" mandates international, interdisciplinary, and interdepartmental collaboration. Furthermore, building trust and confidence between the government and the public, having transparent communication, information sharing, use of advanced research-technology, and plentiful resources are required in the fight against COVID-19.

The Pandemic League of COVID-19: Korea Versus the United States, With Lessons for the Entire World.

Coronavirus disease 2019 (COVID-19) is inflicting a brutal blow on humankind, and no corner of the world has been exempted from its wrath. This study analyzes the chief control measures and the distinctive features of the responses implemented by Korea and the United States to contain COVID-19 with the goal of extracting lessons that can be applied globally. Even though both nations reported their index cases on the same day, Korea succeeded in flattening the curve, with 10 752 cases as of April 28, 2020, whereas the outbreak skyrocketed in the United States, which had more than 1 million cases at the same time. The prudent and timely execution of control strategies enabled Korea to tame the spread of the virus, whereas the United States paid a major price for its delay, although it is too early to render a conclusive verdict. Information pertaining to the number of people infected with the virus and measures instituted by the government to control the spread of COVID-19 was retrieved from the United States Centers for Disease Control and Prevention and the Korea Centers for Disease Control and Prevention websites and press releases. Drawing lessons from both nations, it is evident that the resolution to the COVID-19 pandemic lies in the prudent usage of available resources, proactive strategic planning, public participation, transparency in information sharing, abiding by the regulations that are put into place, and how well the plan of action is implemented.

Discovery of benzisoxazoles as potent inhibitors of chaperone heat shock protein 90.

Heat shock protein 90 (Hsp90) is a molecular chaperone that is responsible for activating many signaling proteins and is a promising target in tumor biology. We have identified small-molecule benzisoxazole derivatives as Hsp90 inhibitors. Crystallographic studies show that these compounds bind in the ATP binding pocket interacting with the Asp93. Structure based optimization led to the identification of potent analogues, such as 13, with good biochemical profiles.