Repurposing fusion inhibitor peptide against SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously evolving. Although several vaccines were approved, this pandemic is still a major threat to public life. Till date, no established therapies are available against SARS-CoV-2. Peptide inhibitors hold great promise for this viral pathogen due to their efficacy, safety, and specificity. In this study, seventeen antiviral peptides which were known to inhibit SARS-CoV-1 are collected and computationally screened against heptad repeat 1 (HR1) of the SARS-CoV-2 spike protein (S2). Out of 17 peptides, Fp13 and Fp14 showed better binding affinity toward HR1 compared to a control peptide EK1 (a modified pan-coronavirus fusion inhibitor) in molecular docking. To explore the time-dependent interactions of the fusion peptide with HR1, molecular dynamics simulation was performed incorporating lipid membrane. During 100 ns MD simulation, structural and energy parameters of Fp13-HR1 and Fp14-HR1 complexes demonstrated lower fluctuations compared to the control EK1-HR1 complex. Furthermore, principal component analysis and free energy landscape study revealed that these two peptides (Fp13 and Fp14) strongly bind to the HR1 with higher affinity than that of control EK1. Tyr917, Asn919, Gln926, lys933, and Gln949 residues in HR1 protein were found to be crucial residues for peptide interaction. Notably, Fp13, Fp14 showed reasonably better binding free energy and hydrogen bond contribution than that of EK1. Taken together, Fp13 and Fp14 peptides may be highly specific for HR1 which can potentially prevent the formation of the fusion core and could be further developed as therapeutics for treatment or prophylaxis of SARS-CoV-2 infection.

Environmentally-friendly thermal and acoustic insulation materials from recycled textiles.

Continuing increase in energy consumption and environmental pollution are some of the main challenges of the 21st century. One of the approaches to overcome these challenges is to increase the use of recycled materials and environmentally-friendly approaches to manufacturing. Thermal and acoustic insulation in buildings and transport vehicles from recycled textiles can play an important role in energy savings and reduction of environmental pollution. Textiles contribute a significant amount to the waste stream since most of these valuable fiber products are discarded after use. These discarded but valuable textiles can be recycled to produce several products including thermal and acoustic insulation materials. In this paper, a comprehensive review of the current state of textile waste generation and its environmental effects, and present progress of using industrial and post-consumer recycled textiles in insulation materials is provided. Mechanism of acoustic and thermal insulation materials of textile fibers are also reviewed. Existing research of some textile waste used as building insulation materials, method of conversion of textile waste into building insulation materials, comparative analysis of different insulation materials and life cycle assessment of textile fibers are assessed.

Does gender diversity mediate the relationships of diversity beliefs and workplace happiness?

Though its intensity varies across cultures, practicing diversity beliefs has become increasingly prevalent in contemporary business organizations. Traditionally, diversity encompasses various aspects such as gender, education, religion, language, age, ethnicity, culture and personality orientation. The current study has demonstrated to identify the mediating effects of gender diversity on diversity beliefs and workplace happiness. The targeted population is made up of full-time Bangladeshi employees working in both public and private organizations. The researchers distributed a questionnaire to 500 employees and obtained 320 valid responses, resulting in a response rate of 64%. The study used the Structural Equation Modelling (SEM) technique to assess the mediating effects and direct effects among the variables. The results demonstrate that gender diversity significantly mediate the associations between diversity beliefs and workplace happiness. This means that employees are more likely to be happy with their jobs if the workplace reflects gender variety in its workforce. The study further demonstrates that workplace happiness significantly affects employees' job satisfaction, engagement and commitment. The present research foregrounds that firms and concerned authorities must increase their various attempts to establish gender-equal policies that appear to be more effective for diversity practice and workplace happiness in work organizations.

A data-driven global flood forecasting system for medium to large rivers.

Losses from catastrophic floods are driving intense efforts to increase preparedness and improve response to disastrous flood events by providing early warnings. Yet accurate flood forecasting remains a challenge due to uncertainty in modeling, calibrating, and validating a useful early warning system. This paper presents the Requisitely Simple (ReqSim) flood forecasting system that includes key variables and processes of basin hydrology and atmospheric forcing in a data-driven modeling framework. The simplicity of the modeling structure and data requirements of the system allows for customization and implementation in any medium to large rain-fed river basin globally, provided there are water level or discharge measurements at the forecast locations. The proposed system's efficacy is demonstrated in this paper through providing useful forecasts for various river basins around the world. This include 3-10-day forecasts for the Ganges and Brahmaputra rivers in South Asia, 2-3-day forecast for the Amur and Yangtze rivers in East Asia, 5-10-day forecasts for the Niger, Congo and Zambezi rivers in West and Central Africa, 6-8-day forecasts for the Danube River in Europe, 2-5-day forecasts for the Parana River in South America, and 2-7-day forecasts for the Mississippi, Missouri, Ohio, and Arkansas rivers in the USA. The study also quantifies the effect of basin size, topography, hydrometeorology, and river flow controls on forecast accuracy and lead times. Results indicate that ReqSim's forecasts perform better in river systems with moderate slopes, high flow persistence, and less flow controls. The simple structure, minimal data requirements, ease of operation, and useful operational accuracy make ReqSim an attractive option for effective real-time flood forecasting in medium and large river basins worldwide.

Evaluation of environmental impacts of cotton polo shirt production in Bangladesh using life cycle assessment.

The textile industry is widely considered as one of the most pollutant-releasing sectors globally. As the world is moving toward sustainability, it is essential to thoroughly assess how a textile product affects the environment. The aim of this study is to investigate the environmental impact of textile manufacturing in Bangladesh using life cycle assessment (LCA) method. A cradle-to-gate LCA was conducted to produce 1000 units of cotton polo shirts following ISO 14040 standards. LCA was also conducted for each final product at every manufacturing stage of cotton polo shirt, including the production of 1000 kg of cotton fibers, 1000 kg of yarn, 1000 kg of grey fabrics, 1000 kg of dyed-finished fabrics, and finally, assembling of 1000 pieces of polo shirts. Inventory analysis revealed that for producing 1000 pieces of polo shirts, 0.12 hector of land, 363.89 kg of cotton fiber, 324.84 kg of yarn, 320.45 kg of knitted fabric, and 299.5 kg of dyed-finished fabrics were required. The study also found that 1550.9 kWh of electricity, 15.47 L of diesel, and 72.54 m3 of natural gas were needed to produce 1000 pieces of polo shirts. The potential environmental impacts were categorized into 12 different types based on the CML 2001 method and calculated using openLCA 2.0 software. The outcomes of LCA revealed considerable environmental impacts in different categories during manufacturing of cotton polo shirts in Bangladesh. For example, the global warming potential (GWP) associated with the manufacturing of 1000 pieces of polo shirts was 1345.97 kg CO2-eq. Among several production stages of polo shirts, the highest contributor of GWP was dyeing section (38.36 %), followed by cotton fiber production (29.32 %) and yarn manufacturing (18.92 %). The obtained data also revealed that for cultivating cotton fibers, manufacturing of yarn and grey fabrics, and finally dyeing-finishing of same quantity fabric (1000 kg), the GWP were 1084.41 kg CO2-eq, 783.67 kg CO2-eq, 145.88 kg CO2-eq, 1723.88 kg CO2-eq, 314.94 kg CO2-eq, respectively. The outcome of the impact assessment will be crucial for decision-making when it comes to taking remedial actions to lessen negative environmental consequences for the sustainable development of textile industry in Bangladesh.

Association of low serum 25-Hydroxy vitamin D [25(OH) d] with hepatic encephalopathy in patients with decompensated liver cirrhosis.

BACKGROUND AND STUDY AIMS: The mechanism of hepatic encephalopathy is complex and has not been conclusively established. Recent studies support lower serum 25-Hydroxy Vitamin D [25(OH) D] levels in patients with hepatic encephalopathy. This study aimed to evaluate the association between serum 25(OH) D and hepatic encephalopathy in patients with decompensated cirrhosis of liver. PATIENTS AND METHODS: A total of 70 cirrhosis patients (35 cases of hepatic encephalopathy and 35 patients without encephalopathy as control, mean age 53.07 ± 12.99 years, 67 % male) were recruited for this study. Assessment of the severity of cirrhosis was done by using a model for end-stage liver disease(MELD) and Child Turcotte Pugh (CTP) scores, and assessment of the severity of hepatic encephalopathy was done according to West Haven criteria. Serum 25 (OH) D level was measured by Chemiluminescent Microparticle Immuno Assay(CMIA). RESULTS: The mean serum 25(OH) D level among hepatic encephalopathy patients was significantly lower in comparison to the control group without encephalopathy (18.76 ± 8.84 nmol/L vs 31.19 ± 13.9 nmol/L, P<0.0001). 91.4 % of hepatic encephalopathy patients had moderate to severe 25(OH)D deficiency as compared to 51.4 % in the control group. There was a significant correlation observed between the severity of the 25 (OH) D deficiency and the severity of liver disease (r =  - 0.35, P = 0.002). No statistically significant difference in serum 25(OH) D levels was found among patients with different hepatic encephalopathy grades (P = 0.416). CONCLUSION: A significant association was found between a low serum 25(OH) D leveland hepatic encephalopathy. It requires further large-scale multicenter studies to establish it as a risk factor and predictor of hepatic encephalopathy.

Leveraging AI and patient metadata to develop a novel risk score for skin cancer detection.

Melanoma of the skin is the 17th most common cancer worldwide. Early detection of suspicious skin lesions (melanoma) can increase 5-year survival rates by 20%. The 7-point checklist (7PCL) has been extensively used to suggest urgent referrals for patients with a possible melanoma. However, the 7PCL method only considers seven meta-features to calculate a risk score and is only relevant for patients with suspected melanoma. There are limited studies on the extensive use of patient metadata for the detection of all skin cancer subtypes. This study investigates artificial intelligence (AI) models that utilise patient metadata consisting of 23 attributes for suspicious skin lesion detection. We have identified a new set of most important risk factors, namely "C4C risk factors", which is not just for melanoma, but for all types of skin cancer. The performance of the C4C risk factors for suspicious skin lesion detection is compared to that of the 7PCL and the Williams risk factors that predict the lifetime risk of melanoma. Our proposed AI framework ensembles five machine learning models and identifies seven new skin cancer risk factors: lesion pink, lesion size, lesion colour, lesion inflamed, lesion shape, lesion age, and natural hair colour, which achieved a sensitivity of 80.46 ± 2.50 % and a specificity of 62.09 ± 1.90 % in detecting suspicious skin lesions when evaluated using the metadata of 53,601 skin lesions collected from different skin cancer diagnostic clinics across the UK, significantly outperforming the 7PCL-based method (sensitivity 68.09 ± 2.10 % , specificity 61.07 ± 0.90 % ) and the Williams risk factors (sensitivity 66.32 ± 1.90 % , specificity 61.71 ± 0.6 % ). Furthermore, through weighting the seven new risk factors we came up with a new risk score, namely "C4C risk score", which alone achieved a sensitivity of 76.09 ± 1.20 % and a specificity of 61.71 ± 0.50 % , significantly outperforming the 7PCL-based risk score (sensitivity 73.91 ± 1.10 % , specificity 49.49 ± 0.50 % ) and the Williams risk score (sensitivity 60.68 ± 1.30 % , specificity 60.87 ± 0.80 % ). Finally, fusing the C4C risk factors with the 7PCL and Williams risk factors achieved the best performance, with a sensitivity of 85.24 ± 2.20 % and a specificity of 61.12 ± 0.90 % . We believe that fusing these newly found risk factors and new risk score with image data will further boost the AI model performance for suspicious skin lesion detection. Hence, the new set of skin cancer risk factors has the potential to be used to modify current skin cancer referral guidelines for all skin cancer subtypes, including melanoma.

CTC together with Shh and Nrf2 are prospective diagnostic markers for HNSCC.

BACKGROUND: The lack of appropriate prognostic biomarkers remains a significant obstacle in the early detection of Head and Neck Squamous Cell Carcinoma (HNSCC), a cancer type with a high mortality rate. Despite considerable advancements in treatment, the success in diagnosing HNSCC at an early stage still needs to be improved. Nuclear factor erythroid 2-related factor 2 (Nrf2) and Sonic Hedgehog (Shh) are overexpressed in various cancers, including HNSCC, and have recently been proposed as possible therapeutic targets for HNSCC. Circulating Tumor Cell (CTC) is a novel concept used for the early detection of cancers, and studies have suggested that a higher CTC count is associated with the aggressiveness of HNSCC and poor survival rates. Therefore, we aimed to establish molecular markers for the early diagnosis of HNSCC considering Shh/Nrf2 overexpression in the background. In addition, the relation between Shh/Nrf2 and CTCs is still unexplored in HNSCC patients. METHODS: In the present study, we selected a cohort of 151 HNSCC patients and categorized them as CTC positive or negative based on the presence or absence of CTCs in their peripheral blood. Data on demographic and clinicopathological features with the survival of the patients were analyzed to select the patient cohort to study Shh/Nrf2 expression. Shh and Nrf2 expression was measured by qRT-PCR. RESULTS: Considering significant demographic [smoking, betel leaf (p-value < 0.0001)] and clinicopathological risk factors [RBC count (p < 0.05), Platelet count (p < 0.05), Neutrophil count (p < 0.005), MCV (p < 0.0001), NLR (p < 0.05), MLR (p < 0.05)], patients who tested positive for CTC also exhibited significant overexpression of Shh/Nrf2 in both blood and tissue compared to CTC-negative patients. A strong association exists between CTCs and tumor grade. Following chemotherapy (a combination of Cisplatin, 5FU, and Paclitaxel), the frequency of CTCs was significantly decreased in patients with HNSCC who had tested positive for CTCs. The Kaplan-Meier plot illustrated that a higher number of CTCs is associated with poorer overall survival (OS) in patients with HNSCC. CONCLUSIONS: Detecting CTCs, and higher expression of Shh and Nrf2 in HNSCC patients' blood, can be a promising tool for diagnosing and prognosticating HNSCC.

Evaluation of antioxidant and anticancer properties of the seed extracts of Syzygium fruticosum Roxb. growing in Rajshahi, Bangladesh.

BACKGROUND: The use of plants and their derived substances increases day by day for the discovery of therapeutic agents owing to their versatile applications. Current research is directed towards finding naturally-occurring antioxidants having anticancer properties from plant origin since oxidants play a crucial role in developing various human diseases. The present study was designed to investigate the antioxidant and anticancer properties of Sygygium fruticosum (Roxb.) (abbreviated as SF). METHODS: The dried coarse powder of seeds of SF was exhaustively extracted with methanol and the resulting crude methanolic extract (CME) was successively fractionated with petroleum ether, chloroform and ethyl acetate to get petroleum ether (PEF), chloroform (CHF), ethyl acetate (EAF) and lastly aqueous (AQF) fraction. The antioxidant activities were determined by several assays: total antioxidant capacity assay, DPPH free radical scavenging assay, hydroxyl radical scavenging assay, ferrous reducing antioxidant capacity and lipid peroxidation inhibition assay. The in vivo anticancer activity of SF was determined on Ehrlich's Ascite cell (EAC) induced Swiss albino mice. RESULTS: All the extractives showed strong antioxidant activities related to the standard. The total antioxidant capacity (TAC) of the fractions was in the following order: EAF>AQF>CME>PEF>CHF. The TAC of EAF at 320 µg/mL was 2.60±0.005 which was significantly higher (p < 0.01) than that of standard catechin (1.37 ± 0.005). The ferrous reducing antioxidant capacity of the extracts was in the following order: EAF>AQF>CME>AA>CHF>PEF. In DPPH free radical scavenging assay, the IC50 value of EAF was 4.85 µg/mL, whereas that of BHT was 9.85 µg/mL. In hydroxyl radical scavenging assay and lipid peroxidation inhibition assay, the EAF showed the most potent inhibitory activity with IC50 of 43.3 and 68.11 µg/mL, respectively. The lipid peroxidation inhibition assay was positively correlated (p < 0 .001) with both DPPH free radical scavenging and hydroxyl radical scavenging assay. The total phenolic contents of SF were also positively correlated (p < 0 .001) with DPPH free radical scavenging, hydroxyl radical scavenging and lipid peroxidation inhibition assay. Based on antioxidant activity, EAF was selected for cytotoxic assay and it was found that EAF inhibited 67.36% (p < 0.01) cell growth at a dose of 50 mg/kg (ip) on day six of EAC cell incubation. CONCLUSIONS: Our results suggest that EAF of seeds of SF possess significant antioxidant and moderate anticancer properties. Seeds of SF may therefore be a good source for natural antioxidants and a possible pharmaceutical supplement.

Structural and functional effects of the L84S mutant in the SARS-COV-2 ORF8 dimer based on microsecond molecular dynamics study.

The L84S mutation has been observed frequently in the ORF8 protein of SARS-CoV-2, which is an accessory protein involved in various important functions such as virus propagation, pathogenesis, and evading the immune response. However, the specific effects of this mutation on the dimeric structure of ORF8 and its impacts on interactions with host components and immune responses are not well understood. In this study, we performed one microsecond molecular dynamics (MD) simulation and analyzed the dimeric behavior of the L84S and L84A mutants in comparison to the native protein. The MD simulations revealed that both mutations caused changes in the conformation of the ORF8 dimer, influenced protein folding mechanisms, and affected the overall structural stability. In particular, the 73YIDI76 motif has found to be significantly affected by the L84S mutation, leading to structural flexibility in the region connecting the C-terminal ß4 and ß5 strands. This flexibility might be responsible for virus immune modulation.  The free energy landscape (FEL) and principle component analysis (PCA) have also supported our investigation. Overall, the L84S and L84A mutations affect the ORF8 dimeric interfaces by reducing the frequency of protein-protein interacting residues (Arg52, Lys53, Arg98, Ile104, Arg115, Val117, Asp119, Phe120, and Ile121) in the ORF8 dimer.  Our findings provide detail insights for further research in designing structure-based therapeutics against the SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Unraveling the impact of ORF3a Q57H mutation on SARS-CoV-2: insights from molecular dynamics.

ORF3a is a conserved accessory protein of SARS-CoV-2, linked to viral infection and pathogenesis, with acquired mutations at various locations. Previous studies have shown that the occurrence of the Q57H mutation is higher in comparison to other positions in ORF3a. This mutation is known to induce conformational changes, yet the extent of structural alteration and its role in the viral adaptation process remain unknown. Here we performed molecular dynamics (MD) simulations of wt-ORF3a, Q57H, and Q57A mutants to analyze structural changes caused by mutations compared to the native protein. The MD analysis revealed that Q57H and Q57A mutants show significant structural changes in the dimer conformation than the wt-ORF3a. This dimer conformer narrows down the ion channel cavity, which reduces Na + or K + permeability leading to decrease the antigenic response that can help the virus to escape the host immune system. Non-bonding interaction analysis shows the Q57H mutant has more interacting residues, resulting in more stability within dimer conformation than the wt-ORF3a and Q57A. Moreover, both mutant dimers (Q57H and Q57A) form a novel salt-bridge interaction at the same position between A:Asp142 and B:Lys61, whereas such an interaction is absent in the wt-ORF3a dimer. We have also noticed that the TM3 domain's flexibility in Q57H is increased because of strong inter-domain interactions of TM1 and TM2 within the dimer conformation. These unusual interactions and flexibility of Q57H mutant can have significant impacts on the SARS-CoV-2 adaptations, virulence, transmission, and immune system evasion. Our findings are consistent with the previous experimental data and provided details information on the structural perturbation in ORF3a caused by mutations, which can help better understand the structural change at the molecular level as well as the reason for the high virulence properties of this variant.Communicated by Ramaswamy H. Sarma.

Reduced IFN-γ levels along with changes in hematologic and immunologic parameters are key to COVID-19 severity in Bangladeshi patients.

The manifestation of coronavirus disease 2019 (COVID-19) severity and mortality has been associated with dysregulation of the immune response, often influenced by racial disparities and conferred by changes in hematologic and immunologic parameters. These biological and hematologic parameters as well as cytokine profiles were investigated in a cohort of 61 COVID-19-positive patients (categorized into mild, moderate, and severe groups) from Bangladesh using standard analytical methods. The data reported that the interleukin (IL)-4 and IL-6 levels were significantly increased, whereas the levels of interferon (IFN)-γ were significantly reduced in patients with severe COVID-19 (p < 0.05) compared with those in patients with mild and/or moderate COVID-19. The extent of erythrocyte sedimentation rate (ESR); neutrophil count; and levels of ferritin, C-reactive protein (CRP), and D-dimer (p < 0.05) were found to be significantly increased, whereas the white blood cell (WBC), lymphocyte, eosinophil, and platelet counts (p < 0.05) were observed to be significantly reduced in patients with severe COVID-19 compared with those in the patients in other 2 groups. Our study exhibited a significantly higher IL-6-to-lymphocyte ratio in patients with severe COVID-19 than in those with mild and moderate COVID-19. The calculated neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and ferritin-to-ESR ratio were significantly increased in patients with severe COVID-19. The increase in the IL-4 and IL-6 levels along with CRP and D-dimer levels may envisage a hyperinflammatory environment and immune dysregulation, which contribute to prolonged viral persistence, leading to severe disease. However, the reduced level of IFN-γ can be attributed to a less fatality toll in Bangladesh compared with that in the rest of the world.

Satellite Remote Sensing of Space-Time Plankton Variability in the Bay of Bengal: Connections to Cholera Outbreaks.

Cholera bacteria exhibit strong association with coastal plankton. Characterization of space-time variability of chlorophyll, a surrogate for plankton abundance, in Northern Bay of Bengal is an essential first step to develop any methodology for predicting cholera outbreaks in the Bengal Delta region using remote sensing. This study quantifies the space-time distribution of chlorophyll, using data from SeaWiFS, in the Bay of Bengal region using ten years of satellite data. Variability of chlorophyll at daily scale, irrespective of spatial averaging, resembles white noise. At a monthly scale, chlorophyll shows distinct seasonality and chlorophyll values are significantly higher close to the coast than in the offshore regions. At pixel level (9 km) on monthly scale, on the other hand, chlorophyll does not exhibit much persistence in time. With increased spatial averaging, temporal persistence of chlorophyll increases and lag one autocorrelation stabilizes around 0.60 for 1296 km(2) or larger areal averages. In contrast to the offshore regions, spatial analyses of chlorophyll suggest that only coastal region has a stable correlation length of 100 km. Presence (absence) of correlation length in the coastal (offshore) regions, indicate that the two regions may have two separate processes controlling the production a phytoplankton This study puts a lower limit on space-time averaging of satellite measured plankton at 1296 km(2)-monthly scale to establish relationships with cholera incidence in Bengal Delta.

Large cerebellopontine angle tuberculoma: a case report.

Tuberculoma involving the cerebellopontine angle is very rare. Preoperative neuroradiological features of such lesions may mimic neoplastic lesions and postoperative histopathological study brings the ultimate diagnosis. Here we present a patient with a large tuberculoma at the cerebellopontine angle who had another small lesion at the right fronto-basal region and was managed by surgical excision of the cerebellopontine angle lesion along with post-surgical antitubercular therapy for 18 months. On the 14th postoperative day, the patient developed status epilepticus, left hemiplegia and left-sided complete hearing loss. Computed tomography showed right frontal oedema. Then he recovered his motor function slowly and incompletely but left-sided hearing loss remained unchanged. Magnetic resonance imaging of the brain at 18 months after surgery showed no residual lesion with right frontal cortical atrophy.

Patient factors associated with the offering of telehealth appointments from primary care physicians among Medicare Beneficiaries: Results from a national survey.

INTRODUCTION: This study assessed patient factors associated with self-reported telehealth offerings from their primary care physicians (PCPs) among Medicare beneficiaries during the COVID-19 pandemic, and compared potential telehealth accessibility of telehealth appointments from PCP by US census region before and during the COVID-19 pandemic. METHODS: Data were from the Medicare Current Beneficiary Survey (MCBS) 2021 Winter COVID-19 Supplement. We conducted a multivariable logistic regression to examine patient-level factors associated with telehealth offerings. RESULTS: Overall, 78% Medicare beneficiaries reported that they had access to telehealth appointments from their PCPs during the COVID-19 pandemic. Majority beneficiary respondents reported to have Internet access (82.1%) and own at least one type of computer device (81.5%). Respondents with Internet access (Adjusted Odds Ratio (AOR) = 1.66, 95% Confidence Interval (CI): 1.38, 2.00; p < 0.0001) and owning a device (AOR = 1.43, 95 %CI: 1.19, 1.72; p < 0.0001) were more likely to report PCP telehealth offerings controlling for patient characteristic variables in the model. Respondents who were female (AOR = 1.16, 95 %CI: 1.02, 1.31; p = 0.020), age group of 65-74 years (AOR = 1.29, 95 %CI: 1.07, 1.56; p = 0.008), income ≥$25,000 (AOR = 1.36, 95 %CI: 1.18 1.56; p < 0.0001), metropolitan residence (AOR = 1.96, 95 %CI: 1.72, 2.24; p < 0.0001), and with a history of weakened immune system (AOR = 1.46, 95 %CI: 1.18, 1.80; p < 0.0001) or diabetes (AOR = 1.20, 95 %CI: 1.06, 1.37; p = 0.005) were more likely to report PCP telehealth offerings compared to their counterparts. Non-Hispanic Black (AOR = 0.70, 95 %CI: 0.58, 0.85; p < 0.0001) (compared to Non-Hispanic-White) and beneficiaries living in the South (compared to those living in the Northwest, Midwest, and West) were less likely to report PCP telehealth offerings. DISCUSSION: Key findings suggested health disparities existed in telehealth offerings from PCPs in terms of Internet access, device owning, age, race/ethnicity, income, residential locations, and census regions. Policy makers should consider these health disparities and provide targeted incentives and/or interventions when expanding and encouraging utilization of telehealth among Medicare beneficiaries.

Heavy metal pollution through hand loom-dyeing effluents and its effect on the community health.

Kumarkhali upazila in Kushtia district of western Bangladesh has become especially vulnerable to dye-effluent pollution over the last two decades. Twenty dyeing effluent samples were obtained at random from various dyeing units and used to determine the heavy metal concentration. The effluent pH, electrical conductivity and total dissolved solids ranged from 3.69 to 13.68, 627 to 7160 mS cm-1 and 4140 to 19800 mg L-1, respectively. In dyeing effluents, the average concentrations of Zn, Cu, Pb, Mn, Fe and Cr ions were 5.50, 82.75, 6.80, 14.27, 66.03 and 65.28 µg mL-1, respectively, while the amount of Cd was barely detectable. Total annual discharges of Cu, Zn, Pb, Mn, Fe and Cr were found to be 21.52, 1.43, 1.77, 3.71, 17.12 and 16.98 kg year-1, respectively, which were high enough to pollute the local environment. According to the survey report, only a minority were aware of public safety measures and proper disposal procedures, though many respondents were conscious of the dangers associated with dyes and chemical substances. Most interviewees (58.33%) used synthetic dyes and other dangerous chemicals throughout the dyeing process, despite the fact that 43.33% did not use hand gloves. A remarkable 80% of respondents were improperly disposing of unused dyes and chemicals. Overall, there was a lack of awareness, right attitude and appropriate behavioural patterns about using dyeing chemicals. To prevent the negative effects of dyeing effluents on the community in the research area, environmental conservation rules should be appropriately implemented.

Structure and dynamics of membrane protein in SARS-CoV-2.

SARS-CoV-2 membrane (M) protein performs a variety of critical functions in virus infection cycle. However, the expression and purification of membrane protein structure is difficult despite tremendous progress. In this study, the 3 D structure is modeled followed by intensive validation and molecular dynamics simulation. The lack of suitable homologous templates (>30% sequence identities) leads us to construct the membrane protein models using template-free modeling (de novo or ab initio) approach with Robetta and trRosetta servers. Comparing with other model structures, it is evident that trRosetta (TM-score: 0.64; TM region RMSD: 2 Å) can provide the best model than Robetta (TM-score: 0.61; TM region RMSD: 3.3 Å) and I-TASSER (TM-score: 0.45; TM region RMSD: 6.5 Å). 100 ns molecular dynamics simulations are performed on the model structures by incorporating membrane environment. Moreover, secondary structure elements and principal component analysis (PCA) have also been performed on MD simulation data. Finally, trRosetta model is utilized for interpretation and visualization of interacting residues during protein-protein interactions. The common interacting residues including Phe103, Arg107, Met109, Trp110, Arg131, and Glu135 in the C-terminal domain of M protein are identified in membrane-spike and membrane-nucleocapsid protein complexes. The active site residues are also predicted for potential drug and peptide binding. Overall, this study might be helpful to design drugs and peptides against the modeled membrane protein of SARS-CoV-2 to accelerate further investigation. Communicated by Ramaswamy H. Sarma.

Evaluation of Antioxidant, Cytotoxic, Anti-Inflammatory, Antiarthritic, Thrombolytic, and Anthelmintic Activity of Methanol Extract of Lepidagathis hyalina Nees Root.

Lepidagathis hyalina Nees is an ethnomedicinally potential Asian herb, locally used to treat cardiovascular diseases and coughs. The study was intended to evaluate qualitative and quantitative investigation to ensure numerous pharmacological properties of methanol extracts of L. hyalina Ness root (MELHR). MELHR manifested strong radical scavenging activity in the reducing power and DPPH (1, 1-diphenyl-2-picrylhydrazyl) assays, and phenol and flavonoid in the quantitative assays. In the study of the thrombolytic assay, MELHR showed moderate explicit percentage of clot lysis (29.39 ± 1.40%) with moderate (135.35 µg/mL) toxic properties. The in vitro anti-inflammatory activity was evaluated by the inhibition of hypotonicity-induced RBC hemolysis, whereas the plant extract exhibited a significant (pp ˂ 0.005) dose-dependent inhibition and the highest inhibition was found 55.01 ± 3.22% at 1000 µg/mL concentration. Moreover, the MELHR also showed significant (p < 0.005) dose-dependent potentiality on protein denaturation which is considered as antiarthritic activity, and the peak inhibition was found significant (71.97 ± 2.71%) at 1000 µg/mL concentration. MELHR also exhibited the dose-dependent and statistically significant anthelmintic potential on aquarium worm (Tubifex tubifex). So, the present investigation suggests that L. hyalina could be the best choice for the management of cardiovascular, inflammation, arthritis, and anthelmintic diseases. Further investigation should be necessary to determine behind the mechanism of bioactivity and therapeutic potential of this plant.

Genetic alterations of Keap1 confers chemotherapeutic resistance through functional activation of Nrf2 and Notch pathway in head and neck squamous cell carcinoma.

Keap1 mutations regulate Nrf2 activity and lead to chemoresistance in cancers. Yet the underlying molecular mechanisms of chemoresistance are poorly explored. By focusing and genotyping head and neck squamous cell carcinoma (HNSCC) that had available pathologic and clinical data, we provide evidence that Keap1 displays frequent alterations (17%) in HNSCC. Functional loss of Keap1 results in significant activation of Nrf2 and promotes cancer cell growth, proliferation, and elevated cancer stem cell (CSCs) self-renewal efficiency and resistance to oxidative stress. Furthermore, decreased Keap1 activity in these cells increased nuclear accumulation of Nrf2 and activation of the Notch pathway, causing enhanced transcriptional alterations of antioxidants, xenobiotic metabolism enzymes, and resistance to chemotherapeutic treatment. Limiting the Nrf2 activity by either Keap1 complementation or by Nrf2 silencing increased the sensitivity to chemotherapy in Keap1-mutated cells and repressed the CSC self-renewal activity. Our findings suggest that Keap1 mutations define a distinct disease phenotype and the Keap1-Nrf2 pathway is one of the leading molecular mechanisms for clinical chemotherapeutic resistance. Targeting this pathway may provide a potential and attractive personalized treatment strategy for overcoming chemotherapeutic resistance conferred by Keap1 mutations.

Detection of SARS-CoV-2 RNA by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) on Self-Collected Nasal Swab Compared With Professionally Collected Nasopharyngeal Swab.

BACKGROUND: Self-collection of nasal swabs for the detection of SARS-CoV-2 RNA by reverse transcription-polymerase chain reaction (RT-PCR) would considerably increase the testing capability and decrease the risk of transmission among healthcare workers (HCW) and the use of personal protective equipment (PPE). OBJECTIVES: This study aimed to evaluate the performance of self-collected nasal swabs compared with professionally collected nasopharyngeal (NP) swabs for detection of SARS-CoV-2 RNA by RT-PCR. MATERIALS AND METHODS: We performed a cross-sectional study where the suspected cases of coronavirus disease 2019 (COVID-19) were instructed about the self-collection of nasal swabs from their mid-turbinate. The results were compared to a nasopharyngeal swab collected by a trained healthcare worker in the same patient at the same sitting. RESULTS: We enrolled 100 participants, of which, 69 (69%) were male and 31 (31%) were female. The median age of the study participant was 36 years. Of the participants, 58 (58%) were symptomatic, and the commonest clinical presentation was cough, which was present in 42 (42%) participants. Out of 100 samples, 31 (31%) professionally collected nasopharyngeal swabs and 28 (28%) self-collected nasal swabs were positive for SARS-CoV-2 by RT-PCR. Out of 31 professionally collected positive samples, three samples were negative in self-collection. Out of 28 self-collected positive samples, no sample was negative in the professional collection. The sensitivity and specificity of self-collected nasal swabs compared to professionally collected nasopharyngeal swabs were 90.32% and 100.00%, respectively. The sensitivity of self-collected nasal was 100% when the cycle threshold (Ct) value of the professionally collected NP swab was less than 30. CONCLUSION: Our study showed that self-collected nasal swabs' sensitivities were similar to professionally collected NP swabs with a high viral load (low Ct value). Hence, this method could be used when the patient is symptomatic and come to the health providers in the early stage of COVID-19 illness.