The association of CYP2C19 LoF alleles with adverse clinical outcomes in stroke patients taking clopidogrel: An updated meta-analysis.

The aggregated risk of recurrent stroke in stroke/transient ischemic attack (TIA) patients carrying CYP2C19 LoF alleles who take clopidogrel has not been investigated recently, and the available research is limited. This study aimed to perform an updated meta-analysis to assess the association between CYP2C19 LoF alleles and the risk of recurrent stroke in patients taking clopidogrel. Databases were searched for the literature on eligible studies. The end points were recurrent stroke, composite vascular events, and bleeding events. Odds ratios (ORs) were calculated using RevMan software, where p < 0.05 was considered statistically significant. Patients carrying CYP2C19 LoF alleles who were treated with clopidogrel had a significantly increased risk of recurrent ischemic stroke compared with non-carriers (OR 2.18, 96% CI 1.80-2.63; p < 0.00001). The risk of recurrent stroke was only significantly different in Asian patients (OR 2.29, 96% CI 1.88-2.80; p < 0.00001) but not in patients of other ethnicities; however, there were a limited number of studies in other ethnic groups. Both observational studies (OR 2.83, 96% CI 2.20-3.65; p < 0.00001) and RCTs (OR 1.48, 96% CI 1.10-1.98; p = 0.009) found associations with a significantly increased risk of recurrent ischemic stroke. Asian stroke patients or TIA patients carrying CYP2C19 LoF alleles and taking clopidogrel were at a significantly higher risk of recurrent ischemic stroke than non-carriers. Significantly increased risk of recurrent ischemic stroke was found in both observational studies and RCTs.

Meta-analysis investigating the impact of the LEPR rs1137101 (A>G) polymorphism on obesity risk in Asian and Caucasian ethnicities.

Obesity is a chronic condition which is identified by the buildup of excess body fat caused by a combination of various factors, including genetic predisposition and lifestyle choices. rs1137101 (A > G) polymorphism in the CHR1 domain of LEPR protein linked to different diseases including obesity. Nevertheless, the connection between this polymorphism and the likelihood of developing obesity has not been determined definitively. Therefore, a meta-analysis was conducted to assess the relationship between rs1137101 and the risk of obesity. The meta-analysis included all studies meeting pre-defined criteria, found through searching databases up until February 2023. A combined odds ratio with a 95% confidence interval was estimated as overall and in continent subgroups for homozygous, heterozygous, recessive, dominant and allelic models using the fixed or the random-effects model. The meta-analysis identified 39 eligible studies with cases and controls (6099 cases/6711 controls) in 38 articles under different ethnic backgrounds. The results indicated a significant relationship between rs1137101 and the likelihood of developing obesity in each of the genetic models [the homozygous model (GG vs. AA: 95% Confidence Interval = 1.12-1.73, Odds Ratio = 1.39, P value = 0.003); the heterozygous model (AG vs. AA: 95% Confidence Interval = 1.07-1.42, Odds Ratio = 1.23, P value = 0.005); the dominant model (AG/GG vs AA: 95% Confidence Interval = 1.10-1.49, Odds Ratio = 1.28, P value = 0.001); the recessive model (GG vs AA/AG: 95% Confidence Interval = 1.02-1.45, Odds Ratio = 1.21, P value = 0.03); and the allelic model (G vs A; 95% Confidence Interval = 1.07-1.33, Odds Ratio = 1.19, P value = 0.002)] tested. Additionally, with an FDR <0.05, all genotypic models demonstrated statistical significance. The association remained significant among subgroups of Asian and Caucasian populations, although analysis in some genetic models did not show a significant association. Begg's and Egger's tests did not show publication biases. In sensitivity analysis, one particular study was found to have an impact on the Recessive model's significance, but other models remained unaffected. The current meta-analysis found significant indications supporting the association between rs1137101 and obesity. To avail a deeper understanding of this association, future research should include large-scale studies conducted in diverse ethnic populations.

Ascaridia galli, a common nematode in semiscavenging indigenous chickens in Bangladesh: epidemiology, genetic diversity, pathobiology, ex vivo culture, and anthelmintic efficacy.

Ascaridia galli is the most common nematode in chickens. Ascaridia galli is highly prevalent in chickens reared in scavenging or semiscavenging systems. Here, we studied the epidemiology, pathology, genetic diversity, ex vivo culture protocol and anthelmintic sensitivity of A. galli prevalent in indigenous chickens in Bangladesh. Through morphological study and molecular analyses, the isolated worms were confirmed as A. galli. Of the chickens examined, 45.6% (178 out of 390) were found infected. The male and young chickens were significantly (P < 0.05) more prone to A. galli infection. Prevalence of the infection was significantly (P < 0.05) lower in the summer season. In heavy infections, A. galli blocked the small intestine. Marked inflammation, increased mucus production and petechial hemorrhages were evident in the small intestine, particularly in the duodenum. Also, there were desquamation and adhesion of the mucosal villi; degeneration, necrosis of the epithelial cells and goblet cell hyperplasia. The mucosal layer was infiltrated mainly with eosinophils and heterophils. We developed a hen egg white-based long-term ex vivo culture protocol which supported the survival and reproduction of A. galli for more than a week. Levamisole (LEV) and ivermectin (IVM) efficiently killed A. galli. However, albendazole (ABZ), mebendazole (MBZ), and piperazine (PPZ) did not kill the worms even at 120 µg/mL and 1mg/mL concentrations, respectively. Taken together, our results suggest that A. galli is highly prevalent in semiscavenging chickens in Bangladesh. Ascaridia galli can be easily maintained ex vivo in egg white supplemented M199 medium. LEV and IVM, but not ABZ, MBZ and PPZ, can be used for treating and controlling A. galli infections in chickens.

An integrated coastal ecosystem monitoring strategy: Pilot case in Naf-Saint Martin Peninsula, Bangladesh.

Rapid population growth creating an excessive pressure on the marine environment and thus monitoring of marine ecosystem is essential. However, due to high technical and financial involvement, monitoring of coastal ecosystem is always challenging in developing countries. This study aims to develop an integrated coastal ecosystem monitoring system that combines scientific sampling, numerical model simulation and citizen science observations to monitor the coastal ecosystem of Bangladesh. This concept of integrated monitoring approach was piloted from January 2022 to April 2023 at the South East coastal zone of Bangladesh. Scientific sampling and numerical model simulations were performed for temperature and salinity data collection. Citizen science approach was employed to collect data on environmental conditions, fisheries, plankton, other marine resources, and plastic pollution. Numerical model simulations and citizen scientists observations of temperature and salinity showed good agreement with the scientifically collected data. In addition, citizen scientists observations on fisheries, plankton, other marine resources and plastic pollution were also in line with the existing database and previous studies. The proposed integrated monitoring approach presents a viable technique, creating a new avenue for coastal and marine ecosystem monitoring where infrastructural facilities are limited.

Electronic aggregated data collection on cervical cancer screening in Bangladesh since 2014: what the data tells us?

INTRODUCTION: To reduce the high prevalence of cervical cancers among the Bangladeshi women, the Government of Bangladesh established a national cervical cancer screening programme in 2005 for women aged 30 to 60 years. The District Health Information System Version 2 (DHIS2) based electronic aggregated data collection system is used since the year 2013. This study summarises data from the year 2014 to 2022 to assess the effectiveness of the electronic data collection system in understanding the outcome of the screening programme. METHODS: This is a descriptive study based on secondary data extracted in MS Excel from the DHIS2-based electronic repository of the national cervical cancer screening programme of Bangladesh. The respondents were women aged 30-60 years, screened for cervical cancer using VIA (Visual Inspection of cervix with Acetic acid) method in 465 government health facilities. The data were collected on the participants' residential location, month and year of screening, name and type of health facilities performing VIA, and VIA screening results. RESULTS: The national screening programme reported a total 3.36 million VIA tests from 465 government hospitals in 8 years (2014 to 2022). The national average VIA-positivity rate was 3.6%, which varied from 1.4 to 9.5% among the districts. This national screening programme witnessed an exponential growth, year after year, with 83.3% increase in VIA test from 2014 to 2022. The primary and the secondary care hospitals were the highest collective contributors of VIA tests (86.2%) and positive cases (77.8%). The VIA-positivity rates in different hospital types varied widely, 7.0% in the medical university hospital, 5.7% in the medical college hospitals, 3.9% in the district/general hospitals, and 3.0% in the upazila health complexes. CONCLUSIONS: A national cervical cancer screening programme using VIA method and a DHIS2-based electronic data collection backbone, is effective, sustainable, and useful to understand the screening coverage, VIA positivity rate and geographic distribution of the participants and case load to initiate policy recommendations and actions. Decentralization of the screening programme and more efforts at the primary and secondary care level is required to increase screening performances.

'Synthesis, antiviral activity, molecular docking, and molecular dynamics studies of ethoxy phthalimide pyrazole derivatives against Cytomegalovirus and Varicella-Zoster virus: potential consequences and strategies for developing new antiviral treatments'.

Substituted ethoxy phthalimide pyrazole derivatives (6a-e) have been produced using a one-pot synthesis technique. Spectral analysis was used to establish the molecular structure of the synthesized compounds, and they were examined in silico and in vitro for their ability to bind to and inhibit replication of the AD-169 strain, the Davis strain of CMV, the OKA strain and the 07/1 strain of Varicella-Zoster virus (VZV). Molecular Docking was used to estimate the binding mechanism and energy of compounds 4, 6a-e to their respective target proteins, thymidine kinase (TK), Varicella-Zoster protease (VZP) of VZV and tegument protein pp71 (TPpp71) of Cytomegalovirus (CMV). The MIC50 and EC50 were utilized to evaluate the antiviral and cytotoxic activities of test compounds in human embryonic lung (HEL) cells against the two reference medicines, Ganciclovir and Acyclovir. The chemicals studied showed a high affinity for binding sites and near binding sites of target proteins by generating H-bonds, carbon-hydrogen bonds, π-anion, π-sulfur, π-sigma, alkyl and π-alkyl interactions. All of the test compounds (6a-e) had higher binding energy than the standard medications. The ADME/T data suggests that these potential inhibitors are less toxic. Drug-protein complexes are structurally compact and demonstrate minimal conformational change in molecular dynamics (MDs) simulations, indicating stability and stiffness. MM-PBSA and post-simulation analysis can predict lead compound active cavity binding stability. By inhibiting multitargeted proteins, these synthetic compounds may improve antiviral therapy. Our research suggests that these unique synthesized chemicals may be useful and accessible adjuvant antiviral therapy for Varicella Zoster and CMV. HighlightsTwo components synthesis of substituted ethoxy phthalimide pyrazole derivatives (6a-e).Tested compounds (6a-e) have antiviral and cytotoxicity activity against CMV and Varicella-Zoster virus (VZV) in HEL cells.Compounds bind to TK, Varicella-Zoster protease (VZP) of VZV, and modeled TPpp71 of Cytomegalovirus (CMV).In comparison to reference drugs, compounds have strong binding free energy and interactions with VZV and CMV protein complexes.The RMSD, RMSF, Rg, residual correlative motion (RCM), No. of hydrogen bonds, protein secondary structure content, per-residue protein secondary structure and MM/PBSA energy calculated for the selected compound with thymidine kinase (TK), VZP of VZV, and modeled tegument protein pp71 (TPpp71) of CMV through MD simulation studies for 50 ns.In comparison to the two reference drugs, ligands/compounds were found to meet the Lipinski rule of five and to have strong biological activity.Communicated by Ramaswamy H. Sarma.

Microplastic contamination in commercial fish feeds: A major concern for sustainable aquaculture from a developing country.

Plastic pollution has become a global issue nowadays. Due to the increased population in developing countries, we largely depend on fish from our aquaculture industry to meet the required protein demand. Though several studies documented plastic ingestion in freshwater and marine organisms, very limited studies have been conducted to elucidate microplastic (MP) contamination in commercial fish feed. Therefore, this study was designed to identify, quantify, and characterize microplastics (MPs) in commercial fish feeds in Bangladesh and assess possible health risks in fish consuming different commercial fish feeds. All fish feed samples were 100 % contaminated with MPs, where the mean abundance of MPs ranged between 500 and 2200 MPs/kg. No significant differences among different types of feeds (e.g., starter, grower, and finisher) were observed in terms of MPs abundance (F = 0.999, p = 0.385). This study revealed that fiber was the most dominant shape of MPs (90 %), while the most dominant color of MPs was red (34 %), followed by black (31 %) and blue (19 %). The 100-1500 µm size class covers 88 % of the total MPs in the collected fish feed samples. Identified polymers in the samples were polyethylene (PE, 37.71 %), polyvinyl chloride (PVC, 27.14 %), polypropylene (PP, 22.08 %), and polyethylene terephthalate (PET, 13.07 %), respectively, where PE and PVC fall under the risk category IV to V. The Pollution load index (PLI) values of all fish feed samples were <10, indicating the risk category of I (low risk). Therefore, this study highly recommended avoiding plastic materials in the packaging and storing purposes of feed ingredients in the feed mills to ensure contamination-free fish feed for sustainable aquaculture.

Dynamics of chemically reactive Carreau nanomaterial flow along a stretching Riga plate with active bio-mixers and Arrhenius catalysts.

Nanomaterial flow has fascinated the concern of scientists across the globe due to its innovative applications in various manufacturing, industrial, and engineering domains. Bearing aforementioned uses in mind, the focal point of this study is to examine the Carreau nanofluid flow configured by the Riga surface with Arrhenius catalysts. Microorganisms are also suspended in nanofluid to strengthen the density of the regular fluid. Time-dependent coupled partial differential equations that represent the flow dynamics are modified into dimensionless patterns via appropriate non-dimensional variables, and handled through an explicit finite difference approach with stability appraisal. The performances of multiple flow variables are examined graphically and numerically. Representation of 3D surface and contour plots for heat transportation and entropy generation are also epitomized. The findings express that the modified Hartmann number strengthens the motion of nanomaterial. Reverse outcomes for heat transport rate and entropy are seen for the radiation variable. Concentration diminishes for chemical reaction variable. Activation energy enhances the concentration of nanomaterial, whereas reduction happens in the movement of microbes for bio-Lewis number. Greater Brinkman variable heightens the entropy.

Insights into the diagnosis, vaccines, and control of Taenia solium, a zoonotic, neglected parasite.

Taenia solium taeniasis/cysticercosis (TSTC) is a foodborne, zoonotic neglected tropical disease affecting predominately low- and middle-income countries. Humans are definitive hosts for T. solium, whereas pigs act as intermediate hosts. Taeniasis, i.e. intestinal infection with adult T. solium in the human host, occurs through ingestion of undercooked pork infected with the larval stage (porcine cysticercosis, PCC). Human cysticercosis occurs after humans ingest T. solium eggs, acting as accidental intermediate hosts. Migration of cysticerci to the human brain results in neurocysticercosis (NCC), manifesting in a variety of clinical symptoms, most notably epilepsy. NCC is the leading cause of acquired epilepsy cases in endemic areas. PCC results in reduced pork value because of condemnation or the risk of condemnation of the meat. Available serological diagnostic tests for porcine and human cysticercosis are characterized by low sensitivity and are not cost-effective. An effective vaccine for T. solium cysticercosis in pigs has been developed, although it is not yet commercially available in all endemic countries, and still no vaccine is available for use in humans. This primer highlights the recent development in the field of diagnostic tests and vaccine production and explores possible strategies for future control and eradication of T. solium. In the absence of highly specific diagnostic tests and human vaccines, treatment of infected pigs and tapeworm carriers and prevention of disease transmission remain the principal means to interrupt the zoonotic cycle of T. solium in endemic countries.

Prevalence of Escherichia coli isolated from oropharynx and trachea of clinically sick poultry and antimicrobial resistance pattern of the strains isolated.

The study was carried out to investigate the isolation of Escherichia coli from tracheal and oropharyngeal swab of clinically sick chickens. The antibiotic susceptibility patterns of the isolates to several antimicrobials were determined with a striking emphasis on oxytetracycline. The PCR technique was applied to detect tetA, tetB, and tetC in the tetracycline-resistant isolates. The isolates were initially screened for their resistance patterns against 6 antimicrobials of six different groups using the disc diffusion technique. The results showed that 41% tracheal, 51% oropharyngeal, and 34% samples from both sites were E. coli positive respectively. Antimicrobial resistance profiling of the isolates revealed that all the isolates were resistant to oxytetracycline and sulphamethoxazole-trimethoprim, and also 90 %, 82.9%, 63.4%, and 39% resistant to ciprofloxacin, amoxicillin, gentamicin, and colistin respectively. Notably, 82.9% isolates (95% CI 68.4%-91.8%) showed resistance to ≥3 groups of antimicrobials that means these were multi-drug resistant. Among the tetracycline-resistant isolates, 85.4% (95% CI 71.2%-93.5%), 29.3% (7.5%-44.6%), and 7.3% (1.8% - 20.1) were positive for tetA, tetB, and tetC genes respectively. The frequency of the isolation of E. coli is greater in oropharyngeal than tracheal and both kinds of samples. Commercial poultry with E. coli strains has acquired extensive resistance to oxytetracycline. This study suggests a possible association between the tetA gene and oxytetracycline resistance in E. coli isolates, but further investigations like knockdown, whole-genome sequencing, and rescue experiments are needed to establish a direct causal relationship.

Therapeutic Potential of Antiviral Peptides against the NS2B/NS3 Protease of Zika Virus.

The NS2B/NS3 protease is highly conserved among various proteases of the Zika virus, making it an important therapeutic target for developing broad-spectrum antiviral drugs. The NS2B/NS3 protease is a crucial enzyme in the replication cycle of Zika virus and plays a significant role in viral maturation and assembly. Inhibiting the activity of this protease can potentially prevent viral replication, making it an attractive target for developing therapies against Zika virus infection. This work screens 429 antiviral peptides in comparison with substrate peptide against the NS2B/NS3 of Zika virus using molecular docking and molecular dynamics (MD) simulation. Based on the docking screening, MD simulation conducted for the best four peptides including AVP0239, AVP0642, AVP0660, and AVP2044, could be effective against NS2B/NS3. These results were compared with the control substrate peptide. Further analysis indicates that AVP0642 and AVP2044 are the most promising candidates. The interaction analysis showed that the catalytic site residues including His51, Asp75, Ser135 and other non-catalytic residues such as Asp129, Asp83, and Asp79 contribute substantial interactions. Hydrogen bonds (41%) and hydrophobic interactions (33%) are observed as the prominent non-covalent interaction prompting the peptide-protein complex formation. Furthermore, the structure-activity relationship (SAR) illustrates that positively charged (Lys, Arg) residues in the peptides dominate the interactions. This study provides the basis for developing novel peptide-based protease inhibitors for Zika virus.

Ascaridia galli infection in chicken: Pathobiology and immunological orchestra.

BACKGROUND: Ascaridia galli is the largest gut-dwelling helminth of chickens, which confers adverse effects on meat and egg production; thus, on the animal protein supply and the economy. Both adult and immature parasites affect gut health, but larval stages play a major role in pathology. AIMS: Here, we present immunology and pathology of A. galli in chickens. MATERIALS AND METHODS: Literatures were surveyed through online platforms such as PubMed, Google Scholar and Researchgate. RESULTS: The larvae cause excessive mucus production, damage to the intestinal gland, hemorrhage, anemia, diarrhea, and malnutrition. The adult worms can cause death by intestinal obstruction and intussusception. Although both cellular and humoral immunity are involved in fighting against ascariasis, the role of naturally acquired immunity is poorly defined. In cellular immunity, Th-2 cytokines (IL-4, IL-5, IL-9, and IL-13), goblet cells (mucin), gut-associated lymphoid tissues, CD8α+ intraepithelial cells, TCRγδ + T cells, and TGF-ß4 form a protective band. Type 2 immunity provides protection by forming a network of endogenous damage-associated molecular patterns, chitin, and parasitic antigens. Among antibodies, IgY is the most prominent in chickens and provides temporary humoral protection. During parasitic infection, infiltration of various immune cells is evident, especially in the intestinal epithelium, lamina propria, and crypts of the duodenum and jejunum. In chickens older than 12 weeks, gradual reduction of worm burden is more successful than the younger birds. Female chickens exert a short-lived but higher level of protection by passing IgY to chicks in the form of egg yolk antibodies. In laying conditions, immunity differs between breeds. This review provides an overview of the silent but inevitable pathological changes induced by A. galli and the interaction of host immunity with the parasite.

Demographic and Clinical Characteristics of Persons With Spinal Cord Injury in Bangladesh: Database for the International Spinal Cord Injury Community Survey 2023.

The study aims to explore the demographic and clinical characteristics of persons with spinal cord injury (SCI) in Bangladesh. A total of 3035 persons with SCI spanning from 2018 to 2022 were included in this cross-sectional study. Information about demographic and clinical variables was obtained from the medical records and verified through telephone calls to ensure accuracy and consistency. Approximately half (48.30%) of the study participants were located in Dhaka Division. The average age of persons with SCI was 38.3 years, with a standard deviation of 15.9 years, and the largest proportion (33.4%) fell within the age range of 18-30 years. Males outnumbered females by nearly 2.5 times. In the study, 59.6% had suffered traumatic injuries, whereas 40.4% had SCI attributable to disease-related causes; 58.1% were diagnosed with tetraplegia and 40.1% with paraplegia. Fall from height (42.1%) and road traffic trauma (27%) were the most common causes of traumatic injuries. Degenerative myelopathy (41.1%) was the most frequent cause of non-traumatic SCI, followed by tumors (27.7%) and tuberculosis (TB; 14.8%). Both traumatic (58.3%) and degenerative (56.7%) causes of SCI commonly affected the cervical spine, whereas TB (24.4%) and tumors (47.5%) had a higher incidence of affecting the dorsal spine. In the absence of a registry or national database for patients with SCI in Bangladesh, this study would serve as representative data for future studies.

Understanding residents' behaviour intention of recycling plastic waste in a densely populated megacity of emerging economy.

Plastic waste is choking our planet, but the recycling rate is still universally low. Understanding factors affecting recycling behaviours can help address this pressing issue. Taking Dhaka as an example, this study explores the determinants of the intentions to recycle plastic waste. We employed the Theory of Planned Behaviour (TPB) and extended it with two additional variables: Moral Norms, and Perceived sufficiency of knowledge and policy support. Survey data of 577 were collected and analysed using PLS-SEM. The findings suggest attitude, perceived behavioural control, moral norms and subjective norms significantly impact recycling intention, among which moral norms (ß = 0.148, p < 0.05) acts even more strongly than subjective norms (ß = 0.12, p < 0.05). Moreover, low level perception of knowledge and policy support makes people perceive less control over recycling behaviour (ß = 0.188, p < 0.05), but actually reinforce their recycling intention (ß = -0.091, p < 0.1). This study enriches the theoretical discussion of TPB, and contributes to the efforts of encouraging plastic recycling in populated megacity of emerging economy.

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.

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.

COVID-19: Modeling Out-of-Home and In-Home Activity Participation during the Pandemic.

Understanding the interaction between in-home and out-of-home activity participation decisions is important, particularly at a time when opportunities for out-of-home activities such as shopping, entertainment, and so forth are limited because of the COVID-19 pandemic. The travel restrictions imposed as a result of the pandemic have had a massive impact on out-of-home activities and have changed in-home activities as well. This study investigates in-home and out-of-home activity participation during the COVID-19 pandemic. Data comes from the COVID-19 Survey for assessing Travel impact (COST), conducted from March to May in 2020. This study uses data for the Okanagan region of British Columbia, Canada to develop the following two models: a random parameter multinomial logit (RPMNL) model for out-of-home activity participation and a hazard-based random parameter duration (HRPD) model for in-home activity participation. The model results suggest that significant interactions exist between out-of-home and in-home activities. For example, a higher frequency of out-of-home work-related travel is more likely to result in a shorter duration of in-home work activities. Similarly, a longer duration of in-home leisure activities might yield a lower likelihood for recreational travel. Health care workers are more likely to engage in work-related travel and less likely to participate in personal and household maintenance activities at home. The model confirms heterogeneity among the individuals. For instance, a shorter duration of in-home online shopping yields a higher probability for participation in out-of-home shopping activity. This variable shows significant heterogeneity with a large standard deviation, which reveals that sizable variation exists for this variable.

A comprehensive review on clinically proven natural products in the management of nerve pain, with mechanistic insights.

Introduction: People are treating their neuropathic pain with several approved and licensed pharmacological drugs. But due to having existing limitations like low efficacy with some side effects, there needs to be a more effective alternative and complementary therapeutic options. Purpose: s: The study was designed to discuss the mechanistic role of several clinically proven natural products that have been shown to play a significant role against different nerve pain or neuropathic pain. Method: ology: Information for this review article was salvaged using several accessible searching databases like SciVerse Scopus ® (Elsevier Properties S. A, USA), Web of Science® (Thomson Reuters, USA), and PubMed® (U.S. National Library of Medicine, USA) considering some search items like - nerve pain, natural products in pain/nerve pain management, clinically proven natural products in pain management, pain-reducing agents and so on. Result: Our study reported the therapeutic efficacy of natural products and their possible mechanism against neuropathic pain in the human body. Natural products widely used to treat neuropathic pain include comfrey root extract ointment, lavender oil, Rose Oil, aromatic essential oil, ginger oil, vitex agnus-castus, peganum oil, and ajwain 10%. Some common pathways are involved in pain relief through sensory stimulation, enzymatic, anti-inflammatory, and pain-related receptor regulation. Conclusion: The present study suggests that the mentioned natural products can be an appropriate choice for the treatment and management of neuropathic pain.

Endosulfan affects embryonic development synergistically under elevated ambient temperature.

In the present study, we determined the developmental toxicity of endosulfan at an elevated ambient temperature using the zebrafish animal model. Zebrafish embryos of various developmental stages were exposed to endosulfan through E3 medium, raised under two selected temperature conditions (28.5 °C and an elevated temperature of 35 °C), and monitored under the microscope. Zebrafish embryos of very early developmental stages (cellular cleavage stages, such as the 64-cell stage) were highly sensitive to the elevated temperature as 37.5% died and 47.5% developed into amorphous type, while only 15.0% of embryos developed as normal embryos without malformation. Zebrafish embryos that were exposed concurrently to endosulfan and an elevated temperature showed stronger developmental defects (arrested epiboly progress, shortened body length, curved trunk) compared to the embryos exposed to either endosulfan or an elevated temperature. The brain structure of the embryos that concurrently were exposed to the elevated temperature and endosulfan was either incompletely developed or malformed. Furthermore, the stress-implicated genes hsp70, p16, and smp30 regulations were synergistically affected by endosulfan treatment under the elevated thermal condition. Overall, the elevated ambient temperature synergistically enhanced the developmental toxicity of endosulfan in zebrafish embryos.

Economic perspectives and policy insights on carbon capture, storage, and utilization for sustainable development.

Carbon capture storage and utilization (CCSU) has the potential to become a key tool to mitigate climate change, thus, aiding in achieving the objectives of the 2015 Paris Agreement. Even though the relevant remediation technology has achieved technical maturity to a certain extent, implementation of CCSU on a larger scale is currently limited because of non-technical parameters that include cost, legalization, lack of storage reservoir, and market mechanism to penalize CO2 emitter. Among these, cost emerges as the primary barrier to the dissemination of CCSU. Hence, necessary policy frameworks and incentives must be provided by governing agencies to enable faster dissemination of carbon capture and utilization (CCU) and carbon capture and storage (CCS) globally. Meanwhile, strict implementation of a carbon tax across nations and market demand for products generated using captured CO2 can aid in the fast adoption of CCU and CCS. This review assessed the economic feasibility and sustainability of CCS and CCU technologies to identify the barriers to commercializing these technologies.