Evolutionary Pattern of Asian HIV-1 Subtype B from 1990 to 2007: In Silico Analysis Based on Envelop Protein

HIV-1 envelop gene is a major target for vaccine development. Envelop protein and its V3 loop is shown to be important determinant of HIV-1 pathogenecity. Herein, the evolutionary pattern of most prevalent HIV-1 subtype B in Asia is determined by analyzing envelop protein and V3 domain based on the 40 randomly selected sequences of HIV-1 from database (Los Alamos), divided into four groups since 1990–2007. Construction of envelop protein phylogeny by using MEGA 5 exhibit the active mutation pattern, increase in potential N-glycosylation sites which were predicted by using online software SignalP-NN. An online available tool Drawgram was used for multiple sequence alignment (MSA) of HIV-1 subtype B envelop region and V3 loop while the alignment was rechecked by using CLUSTAL W and further was analyzed for GPGX motif and conserved region in V3 loop. Variation at fourth position of the GPGX motif and 60% conservation was found in V3 loop. Hence, this diversifying pattern of envelop protein in the Asia formulates the HIV-1 strains more pathogenic during the period of 17 years. These findings might help in understanding significant structural and functional constrains of the mutant viral strains and ultimately in vaccine development

Conceptos erróneos comunes sobre COVID-19 entre los profesionales de la salud: una encuesta transversal global en línea.

Background: The COVID-19 pandemic has taken the world by storm, with cases continuously increasing by the hour and with a shortage of information regarding the virus available to the general public. Despite the availability of trusted online sources, there are still misconceptions relating to the virus floating around. This study aimed to find out the level of misconceptions among healthcare professionals (HCPs) worldwide about the ensuing COVID-19 pandemic. Materials and Methods: A descriptive cross sectional study was conducted through a global online survey. The self-administered questionnaire was designed and registered at an online website (Kwiksurveys). A total of 652 participants from 35 different countries across the world responded. Statistical analysis was performed using SPSS version 23. Socio-demographic and discipline characteristics were compared with the help of the chi-square test and univariate and multivariate logistic regression to find significant relationships. Results: Among all HCPs, general physicians (61.2%) were the most common respondents. The responses from females (63.3%) almost doubled those of men, and nearly half of the participants were working in private institutes (49.2%). Additionally, the major source of information used by HCPs about COVID-19 was social media (55.4%). Regarding misconception assessment, 71.6% of participants had correct concepts regarding COVID-19. However, 28.4% had incorrect information. Female HCPs were 1.49 times more likely to have correct concepts compared to males (OR=1.49, 95% CI=1.04-2.14). Conclusions: The majority of the HCPs were keeping themselves up-to-date with current information concerning the knowledge, prevention, and hygiene practices of COVID-19 infection. However, some misconceptions are deeply rooted in the mindsets of HCPs worldwide and need to be addressed by the continuous professional development of HCPs. The availability of reliable sources of information on the pandemic should be encouraged, with adequate explanations also available to the general public in simple terms.Antecedentes: la pandemia de COVID-19 ha asolado al mundo, con casos que aumentan continuamente  y con una escasez de información sobre el virus disponible para el público en general. A pesar de la disponibilidad de fuentes confiables en línea, todavía hay conceptos erróneos relacionados con el virus. Este estudio tuvo como objetivo dilucidar el nivel de ideas erróneas entre los profesionales de la salud (PS) en todo el mundo sobre la pandemia de COVID-19. Material y Métodos: Se realizó un estudio descriptivo de corte transversal a través de una encuesta global en línea. El cuestionario autoadministrado fue diseñado y registrado en un sitio web en línea (Kwiksurveys). Respondieron un total de 652 participantes de 35 países. El análisis estadístico se realizó con el programa SPSS versión 23. Las características sociodemográficas y disciplinarias se compararon con la ayuda de la la prueba de chi-cuadrado y la regresión logística univariada y multivariada para encontrar relaciones significativas. Resultado: Entre todos los profesionales de la salud, los médicos generales (61,2%) fueron los que más respondieron. Las respuestas de las mujeres (63,3%) casi duplicaron las de los hombres, y casi la mitad de los participantes trabajaban en institutos privados (49,2%). Además, la principal fuente de información utilizada por los profesionales de la salud sobre COVID-19 fueron las redes sociales (55,4%). En cuanto a los conceptos erróneos, el 71,6% de los participantes tenían conceptos correctos con respecto a COVID-19. Sin embargo, el 28.4% poseía información incorrecta. Los profesionales de la salud mujeres tenían 1.49 veces más probabilidades de tener conceptos correctos en comparación con los hombres (OR = 1.49, IC 95% = 1.04-2.14). Conclusion: La mayoría de los profesionales de la salud se mantuvieron actualizados con la información actual sobre el conocimiento, la prevención y las prácticas de higiene de la infección por COVID-19. Sin embargo, algunos conceptos erróneos están profundamente arraigados en la mentalidad de los PS en todo el mundoy deben abordarse mediante el continuo desarrollo profesional de los PS. Se debe alentar la disponibilidad de fuentes confiables de información sobre la pandemia, con explicaciones adecuadas también disponibles para el público en general en términos simples

Hepatitis C Virus Infection: Molecular Pathways to Insulin resistance

Chronic Hepatitis C virus has the potential of inducing insulin resistance and type 2 Diabetes Mellitus in vitro as well as in vivo . Structural and non-structural proteins of HCV modulate cellular gene expression in such a way that insulin signaling is hampered, concomitantly leads toward diabetes mellitus. A number of mechanisms have been proposed in regard to the HCV induced insulin resistance involving the upregulation of Inflammatory cytokine TNF-α, hypophosphorylation of IRS-1 and IRS-2, phosphorylation of Akt, up-regulation of gluconeogenic genes, accumulation of lipids and targeting lipid storage organelles. This review provides an insight of molecular mechanisms by which HCV structural and non-structural proteins can induce insulin resistance

Safety and efficacy of bendamustine in the conditioning regimen for autologous stem cell transplantation in patients with relapsed/refractory lymphoma

Background: Bendamustine is an attractive option for the management of both de novo and relapsed lymphomas. It is being increasingly used in the conditioning regimen for autologous stem cell transplantation (SCT) and can be an alternative to the traditionally-used carmustine. In this study, we aimed to determine the safety and efficacy of bendamustine in the conditioning regimen for autologous SCT in refractory/relapsed lymphomas.Methods: We designed a descriptive study to evaluate bendamustine in combination with etoposide, cytarabine, and melphalan (BeEAM) in the conditioning regimen for autologous SCT.Results: Fourteen patients (median age, 28 yr) with Hodgkin\u27s lymphoma (HL) (N=8), non-Hodgkin\u27s lymphomas (NHL) (N=5), or peripheral T-cell lymphoma, not otherwise specified (PTCL NOS) (N=1) were included in the study. A median number of 5.95×106 CD34+ cells/kg were transfused. Median times to absolute neutrophil count and platelet engraftment were 17 days and 24 days, respectively. The 100-day transplantation mortality rate was 28% (4 patients). Eight patients (57.14%) had GII-III acute kidney injury, four patients (28.5%) had GIII-IV hyperbilirubinemia, and twelve patients (85%) had GII-III diarrhea. After 3 months, 37% (5 patients) and 21.4% (3 patients) demonstrated complete response and partial response, respectively. The median follow-up was 5.5 months (15 days-19 mo). At the final follow-up, 7 patients (50%) were alive and in CR.Conclusion: Our study showed that bendamustine is a potentially toxic agent in the conditioning regimen for autologous SCT, resulting in significant liver, kidney, and gastrointestinal toxicity. Further studies are required to assess its safety and efficacy at reduced doses

Sporadic early onset colorectal cancer in Pakistan: A case- control analysis of microsatellite instability

Background: Early onset sporadic colorectal cancer (CRC) is a biologically and clinically distinct entity hypothesized to exhibit differences in histological features and microsatellite instability (MSI) as compared to typical onset CRC. This study compared the MSI status, mismatch repair enzyme deficiency and clinicopathological features of early onset (aged ≤45 years) with controls (\u3e45 years).Materials and Methods: A total of 30 cases and 30 controls were analyzed for MSI status using the Bethesda marker panel. Using antibodies against hMLH1, hMSH2 and hMSH6, mismatch repair protein expression was assessed by immunohistochemistry. Molecular characteristics were correlated with clinicopathological features.Results: The early onset sporadic CRCs were significantly more poorly differentiated tumors, with higher N2 nodal involvement and greater frequency of signet ring phenotype than the typical onset cases. MSI was observed in 18/30 cases, with 12/18 designated as MSI-high (MSI-H) and 6/18 designated as MSI-low (MSI-L). In the control group, 14 patients exhibited MSI, with 7 MSI-H and 7 MSI-L. MSI tumors in both cases and controls exhibited loss of hMLH1, hMSH2 and hMSH6. MSS tumors did not exhibit loss of expression of MMR proteins, except hMLH1 protein in 3 controls. No statistically significant difference was noted in MSI status or expression of MMR proteins in cases versus controls.Conclusions: Microsatellite status is comparable between early and typical onset sporadic CRC patients in Pakistan suggesting that differences in clinicopathological features between these two subsets are attributable to other molecular mechanisms

MILK: carrier of heavy metals from crops through ruminant body to human beings

Exposure of heavy metals to humans is higher today than ever before in modern history due to continuously increasing industrialization around the globe. Industrial wastes are rich in heavy metals and these wastes are discharged near agricultural fields or mixed with soil, from where these metals are taken up by the crops and are finally transported to humans. Due to this increasing threat of heavy metals contamination in food, it is necessary to analyze the food before consumption. Content of selected metals (Cd, Cr, Cu, Pb and Zn) in cow milk is determined in this study. To investigate the possible pathways of these metals to reach in milk; fodder supplied to these cows was analyzed besides analysis of soil samples on which this fodder was grown. Pearson correlation among metal contents in soil-forage and forage-milk was also determined to check the route of transfer of these metals from soil to forage and from forage to milk. It was found that a strong correlation (p < 0.5) exists for Cr, Cd, Cu and Zn. This shows that these metals are mainly transferred through soil. However, a weak correlation was found for Pb, which shows that Pb is introduced into forage through some other source (automobile exhaust etc.). A comparison of present study is also done with previously reported work from other countries on metal contents in milk and findings of both the studies were in good agreement mutually

Clinical Profile of Mortality and Treatment Profile of Survival in Patients with COVID-19 Pneumonia Admitted to Dubai Hospital

Background: Most COVID-19 studies conclude old age and coexisting illnesses as mortality determinants owing to different populations or methodologies, or omitting factors affecting outcomes. Methods: We analyzed COVID-19 patients’ data (N = 391) of Dubai Hospital between January 1, 2020 and June 30, 2020. Results: Only 19 patients (4.8%) were UAE nationals, while 372 (95.2%) were expatriates. Median age was 48 (interquartile range, 40–56) years; 22% were &#x3c;40 years, and only 16.6% were female. Cough was the most common symptom (78.7%), fever was 77.4%, and gastrointestinal symptoms were least common (13.8%). Approximately 95% had elevated C-reactive protein (CRP) and D-dimers (79%), lymphocytopenia 47.3%, and thrombocytopenia 13.8%. Mortality was 30% for the total sample and 50% in ICU patients. ICU patients were older than non-ICU (age; 49.6 ± 10.9 vs. 46.7 ± 12.7 years, p = 0.04). Eighty-five percent of ICU patients required invasive mechanical ventilation, 78% vasopressors, 88% sedation, 84% muscle paralysis, while none require any of these in the medical group. Survivors had fewer patients with sedatives (p = 0.01). The median length of stay in the hospital was 19 days, ICU stays 14 days, and ventilator 11 days. The Mann-Whitney test showed that survivors spent more days in the ICU (median [IQR] 18 [6.5–29.5] vs. 11 [4–18], p value 0.003) and the hospital (32 [14.5–49.5] vs. 14 [7–21], p value 0.001) than nonsurvivors. Ferritin and D-dimers were higher in nonsurvivors, but CRP was lower in nonsurvivors (ferritin (ng/mL) median (IQR) 1,434 (661.5–2206.5) versus 1,362 (630–2,094), p value = 0.017, CRP (mg/L) 118.7 (53.4–184) versus 134.9 (66.5–203.2), p value 0.001 and D-dimer (µg/mL) 1.54 (0–3.13) versus 1.09 (0–2.51), p value = 0.001). Multiple logistic regression analysis determined age, fever on admission, use of oxygen, mechanical ventilation, and steroids as predictors of survival. Conclusions: COVID-19 patients were young males with pre-existing conditions. Ferritin, CRP, and D-dimers were higher in nonsurvivors. Treatment with chloroquine, antivirals, and anticoagulation was not different between survivors and nonsurvivors. Steroid use was a survival predictor

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions