Influence of folic acid and vitamin B12 supplementation on arsenic methylation: A double-blinded, placebo-controlled trial in Bangladeshi children.

BACKGROUND: Inorganic arsenic is metabolized to monomethyl- (MMAs) and dimethyl- (DMAs) species via one-carbon metabolism (OCM); this facilitates urinary arsenic elimination. OCM is influenced by folate and vitamin B12 and previous randomized control trials (RCTs) showed that folic acid (FA) supplementation increases arsenic methylation in adults. This RCT investigated the effects of FA + B12 supplementation on arsenic methylation in children, a key developmental stage where OCM supports growth. METHODS: A total of 240 participants (8-11 years, 53 % female) drinking from wells with arsenic concentrations > 50 µg/L, were encouraged to switch to low arsenic wells and were randomized to receive 400 µg FA + 5 µg B12 or placebo daily for 12-weeks. Urine and blood samples were collected at baseline, week 1 (only urine) and week 12. Generalized estimated equation (GEE) models were used to assess treatment effects on arsenic species in blood and urine. RESULTS: At baseline, the mean ± SD total blood and urinary arsenic were 5.3 ± 2.9 µg/L and 91.2 ± 89.5 µg/L. Overall, total blood and urine arsenic decreased by 11.7% and 17.6%, respectively, at the end of follow up. Compared to placebo, the supplementation group experienced a significant increase in the concentration of blood DMAs by 14.0% (95% CI 5.0, 25.0) and blood secondary methylation index (DMAs/MMAs) by 0.19 (95% CI: 0.09, 0.35) at 12 weeks. Similarly, there was a 1.62% (95% CI: 0.43, 20.83) significantly higher urinary %DMAs and -1.10% (95% CI: -1.73, -0.48) significantly lower urinary %MMAs in the supplementatio group compared to the placebo group after 1 week. The direction of the changes in the urinary %iAs, %MMAs, and %DMAs at week 12 were consistent with those at week 1, though estimates were not significant. Treatment effects were stronger among participants with higher baseline blood arsenic concentrations. Results were consistent across males and females, and participants with higher and lower folate and B12 status at baseline. CONCLUSION: This RCT confirms that FA + B12 supplementation increases arsenic methylation in children as reflected by decreased MMAs and increased DMAs in blood and urine. Nutritional interventions may improve arsenic methylation and elimination in children, potentially reducing arsenic toxicity while also improving nutritional status.

Harnessing THz Technology: Biosensor for Highly Accurate Cervical Cancer Cell Detection via Refractive Index.

In order to rapidly identify various species of cancer cells in the tissues of person, a unique diamond shaped hollow-core photonic crystal fiber (PCF)-formed by optical waveform is developed and computationally studied. In this investigation, we found the most prevalent cancers, such as HeLa-derived cervical carcinoma. Since normal and cancer cells differ in their refractive indices (RIs), other significant optical properties can be assessed using this information. With the use of the finite element method, a computational tool for solving simultaneous equations, the defining characteristics the suggested cancer cell sensor are examined using COMSOL-Multiphysics software. Additionally, strict mesh parts are used to preserve the utmost level of modeling realism. At 2.4 THz, the PCF detector attains a Relative Sensitivity of around 97.51% and 96.29%, Confinement Loss of 6.1 × 10 -09db/m and 4.39 × 10-07db/m with respect to cervical carcinoma cell and cervical normal cell. The straightforward PCF structure provides a wide chance of application using the continuing fabrication technique, based on these conventional values of performance indices. This biosensor utilizes the distinctive refractive characteristics of cancer cells, providing a highly accurate and dependable approach for the early identification of cervical cancer. This has the potential to significantly transform the process of cervical cancer screening. The novel method boosts the ability to detect and identify certain conditions, leading to increased diagnostic capabilities for early treatment and better results for patients.

Dysbiosis of the gut microbiota and its effect on α-synuclein and prion protein misfolding: consequences for neurodegeneration.

Abnormal behavior of α-synuclein and prion proteins is the hallmark of Parkinson's disease (PD) and prion illnesses, respectively, being complex neurological disorders. A primary cause of protein aggregation, brain injury, and cognitive loss in prion illnesses is the misfolding of normal cellular prion proteins (PrPC) into an infectious form (PrPSc). Aggregation of α-synuclein causes disruptions in cellular processes in Parkinson's disease (PD), leading to loss of dopamine-producing neurons and motor symptoms. Alteration in the composition or activity of gut microbes may weaken the intestinal barrier and make it possible for prions to go from the gut to the brain. The gut-brain axis is linked to neuroinflammation; the metabolites produced by the gut microbiota affect the aggregation of α-synuclein, regulate inflammation and immunological responses, and may influence the course of the disease and neurotoxicity of proteins, even if their primary targets are distinct proteins. This thorough analysis explores the complex interactions that exist between the gut microbiota and neurodegenerative illnesses, particularly Parkinson's disease (PD) and prion disorders. The involvement of the gut microbiota, a complex collection of bacteria, archaea, fungi, viruses etc., in various neurological illnesses is becoming increasingly recognized. The gut microbiome influences neuroinflammation, neurotransmitter synthesis, mitochondrial function, and intestinal barrier integrity through the gut-brain axis, which contributes to the development and progression of disease. The review delves into the molecular mechanisms that underlie these relationships, emphasizing the effects of microbial metabolites such as bacterial lipopolysaccharides (LPS), and short-chain fatty acids (SCFAs) in regulating brain functioning. Additionally, it looks at how environmental influences and dietary decisions affect the gut microbiome and whether they could be risk factors for neurodegenerative illnesses. This study concludes by highlighting the critical role that the gut microbiota plays in the development of Parkinson's disease (PD) and prion disease. It also provides a promising direction for future research and possible treatment approaches. People afflicted by these difficult ailments may find hope in new preventive and therapeutic approaches if the role of the gut microbiota in these diseases is better understood.

Posterior reversible encephalopathy syndrome associated with dengue fever induced intrauterine death: A case report.

In recent years dengue fever has become a major health concern specifically due to its diverse presentation and adverse outcome. Progression from mild febrile illness to a severe systemic illness may occur in dengue fever including neurological disorder. Here, we report an unusual and rare case of a 20-year-old mother who developed posterior reversible encephalopathy syndrome (PRES) following dengue fever induced intrauterine death and septic shock.

Nectandrin B significantly increases the lifespan of Drosophila - Nectandrin B for longevity.

Phytochemicals are increasingly recognized in the field of healthy aging as potential therapeutics against various aging-related diseases. Nutmeg, derived from the Myristica fragrans tree, is an example. Nutmeg has been extensively studied and proven to possess antioxidant properties that protect against aging and alleviate serious diseases such as cancer, heart disease, and liver disease. However, the specific active ingredient in nutmeg responsible for these health benefits has not been identified thus far. In this study, we present evidence that Nectandrin B (NecB), a bioactive lignan compound isolated from nutmeg, significantly extended the lifespan of the fruit fly Drosophila melanogaster by as much as 42.6% compared to the control group. NecB also improved age-related symptoms including locomotive deterioration, body weight gain, eye degeneration, and neurodegeneration in aging D. melanogaster. This result represents the most substantial improvement in lifespan observed in animal experiments to date, suggesting that NecB may hold promise as a potential therapeutic agent for promoting longevity and addressing age-related degeneration.

Addressing diffuse water pollution from agriculture: Do governance structures matter for the nature of measures taken?

Nutrient pollution of freshwaters from agriculture is a key barrier to achieving the water quality goals of the European Water Framework Directive (WFD). Governance research suggests that governance structures can support the planning of water quality measures. However, it is widely unclear how specific governance structures affect the actual nature of practical measures taken for addressing the "wicked problem" of diffuse nutrient pollution. This study analyses how the extent of consensual policy styles, organizational and program integration, participatory governance, and the capacities of public authorities are related to the substance of practical measures taken (effect-vs. source-based measures) and the choice of policy instruments (e.g., sermons, carrots, sticks). Based on a comparative case study design including six country cases, document analyses, and expert interviews, we find no clear-cut relationships between the country's governance structures and the types of measures chosen or any trend of a combined effect. This suggests that, in the case of the WFD, governance structures are less important than expected or that different governance structures compensate for the effects on the level of practical measures taken and policy instruments chosen. These results question the dominant assumption that these governance structures matter (a lot) in wicked problem solving and may hint to additional context factors these governance structures are embedded in.

Targeted delivery of RNAi to cancer cells using RNA-ligand displaying exosome

Exosome is an excellent vesicle for in vivo delivery of therapeutics, including RNAi and chemical drugs. The extremely high efficiency in cancer regression can partly be attributed to its fusion mechanism in delivering therapeutics to cytosol without endosome trapping. However, being composed of a lipid-bilayer membrane without specific recognition capacity for aimed-cells, the entry into nonspecific cells can lead to potential side-effects and toxicity. Applying engineering approaches for targeting-capacity to deliver therapeutics to specific cells is desirable. Techniques with chemical modification in vitro and genetic engineering in cells have been reported to decorate exosomes with targeting ligands. RNA nanoparticles have been used to harbor tumor-specific ligands displayed on exosome surface. The negative charge reduces nonspecific binding to vital cells with negatively charged lipid-membrane due to the electrostatic repulsion, thus lowering the side-effect and toxicity. In this review, we focus on the uniqueness of RNA nanoparticles for exosome surface display of chemical ligands, small peptides or RNA aptamers, for specific cancer targeting to deliver anticancer therapeutics, highlighting recent advances in targeted delivery of siRNA and miRNA that overcomes the previous RNAi delivery roadblocks. Proper understanding of exosome engineering with RNA nanotechnology promises efficient therapies for a wide range of cancer subtypes.

A genetically encoded BRET-based SARS-CoV-2 Mpro protease activity sensor.

The main protease, Mpro, is critical for SARS-CoV-2 replication and an appealing target for designing anti-SARS-CoV-2 agents. Therefore, there is a demand for the development of improved sensors to monitor its activity. Here, we report a pair of genetically encoded, bioluminescence resonance energy transfer (BRET)-based sensors for detecting Mpro proteolytic activity in live cells as well as in vitro. The sensors were generated by sandwiching peptides containing the Mpro N-terminal autocleavage sites, either AVLQSGFR (short) or KTSAVLQSGFRKME (long), in between the mNeonGreen and NanoLuc proteins. Co-expression of the sensors with Mpro in live cells resulted in their cleavage while mutation of the critical C145 residue (C145A) in Mpro completely abrogated their cleavage. Additionally, the sensors recapitulated the inhibition of Mpro by the well-characterized pharmacological agent GC376. Further, in vitro assays with the BRET-based Mpro sensors revealed a molecular crowding-mediated increase in the rate of Mpro activity and a decrease in the inhibitory potential of GC376. The sensors developed here will find direct utility in studies related to drug discovery targeting the SARS-CoV-2 Mpro and functional genomics application to determine the effect of sequence variation in Mpro.

Bioactive potentiality of secondary metabolites from endophytic bacteria against SARS-COV-2: An in-silico approach.

Five endophytic bacterial isolates were studied to identify morphologically and biochemically, according to established protocols and further confirmed by 16S rDNA Sanger sequencing, as Priestia megaterium, Staphylococcus caprae, Neobacillus drentensis, Micrococcus yunnanensis, and Sphingomonas paucimobiliz, which were then tested for phytohormone, ammonia, and hydrolytic enzyme production. Antioxidant compounds total phenolic content (TPC), and total flavonoid content (TFC) were assessed by using bacterial crude extracts obtained from 24-hour shake-flask culture. Phylogenetic tree analysis of those identified isolates shared sequence similarities with the members of Bacillus, Micrococcus, Staphylococcus, and Pseudomonas species, and after GenBank submission, accession numbers for the nucleotide sequences were found to be MW494406, MW494408, MW494401, MW494402, and MZ021340, respectively. In silico analysis was performed to identify their bioactive genes and compounds in the context of bioactive secondary metabolite production with medicinal value, where nine significant bioactive compounds according to six different types of bioactive secondary metabolites were identified, and their structures, gene associations, and protein-protein networks were analyzed by different computational tools and servers, which were reported earlier with their antimicrobial, anti-infective, antioxidant, and anti-cancer capabilities. These compounds were then docked to the 3-chymotrypsin-like protease (3CLpro) of the novel SARS-COV-2. Docking scores were then compared with 3CLpro reference inhibitor (lopinavir), and docked compounds were further subjected to ADMET and drug-likeness analyses. Ligand-protein interactions showed that two compounds (microansamycin and aureusimine) interacted favorably with coronavirus 3CLpro. Besides, in silico analysis, we also performed NMR for metabolite detection whereas three metabolites (microansamycin, aureusimine, and stenothricin) were confirmed from the 1H NMR profiles. As a consequence, the metabolites found from NMR data aligned with our in-silico analysis that carries a significant outcome of this research. Finally, Endophytic bacteria collected from medicinal plants can provide new leading bioactive compounds against target proteins of SARS-COV-2, which could be an effective approach to accelerate drug innovation and development.

Virucidal Effect of Povidone Iodine on SARS-CoV-2 in Nasopharynx: An Open-label Randomized Clinical Trial.

To assess the virucidal effect of povidone iodine (PVP-I) on severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) located in the nasopharynx and suitable dose-formulation for nasal application were the purpose of this clinical trial. This single-center, open-label randomized clinical trial with a 7-arm parallel-group design was conducted in Dhaka Medical College (DMC) Hospital. A total of 189 reverse transcription-polymerase chain reaction (RT-PCR)-confirmed SARS CoV-2 positive cases aged 12-90 years with symptoms was sequentially enrolled following randomization. Nasopharyngeal clearance of SARS-CoV-2 was tested against PVP-I nasal irrigation (NI) at diluted concentrations of 0.4%, 0.5% and 0.6%, and PVP-I nasal spray (NS) at diluted concentrations of 0.5% and 0.6%. All groups were compared to the corresponding controls (distilled water). Written informed consent was ensured before participation. All procedures were conducted in after ethical clearance from the Ethical Review Board and in accordance with the Declaration of Helsinki. Viral clearance in a repeat RT-PCR (qualitative) was the primary outcome, and occurrence of any adverse event following administration of testing drug was considered as the secondary outcome. Analysis was performed using SPSS (Version 26). All cases were randomized into seven groups and each group consists of 27-patient. Mean age of the cases 43.98 ± 12.67 years (SD). All strength of NI were effective in nasopharyngeal clearance compared to the control (0.4%, p = 0.006; 0.5%, p < 0.001; and 0.6%, p = 0.018). Similarly, all strength of the NS is also effective than control (0.5%, p = < 0.001; and 0.6%, p ≤ 0.001). Highest nasopharyngeal clearance was observed in patients using 0.5% NI (n = 25, 92.6%, p = 0.018). Nasal irritation was the single most adverse event recorded in this trial and found in two patients using 0.4%, and 0.6% PVP-I NI, respectively. Both PVP-I NS and NI are effective for nasopharyngeal clearance in-vivo. However, further community trials are needed to repurpose these solutions as preventive agents against SARS-CoV2. Ethical clearance memo no ERC-DMC/ECC/2020/93. Trial registration NCT Identifier number NCT04549376. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03106-0.

Characterization, molecular modeling and pharmacology of some 2́-hydroxychalcone derivatives as SARS-CoV-2 inhibitor.

This work presented the microwave assisted synthesis of six new 2́-hydroxychalcones and their characterization based on FTIR, UV-Vis, 1H NMR, and mass spectral analysis. Quantum chemical studies confirmed the structures of prepared chalcones. Antioxidant, in vitro antimicrobial and in silico antiviral studies have been performed to evaluate their biological performance. Results of molecular docking of prepared 2́-hydroxychalcones against SARS-CoV-2 (7BQY) main protease disclosed their inhibition which is comparable to standard, remdesivir and better than hydroxychloroquine (HCQ). ADMET prediction revealed them to be non-carcinogenic and relatively safe.

A Genetically Encoded BRET-based SARS-CoV-2 Mpro Protease Activity Sensor

The SARS-CoV-2 main protease, Mpro, is critical for its replication and is an appealing target for designing anti-SARS-CoV-2 agents. In this regard, a number of assays have been developed based on its cleavage sequence preferences to monitor its activity. These include the usage of Fluorescence Resonance Energy Transfer (FRET)-based substrates in vitro and a FlipGFP reporter, one which fluoresces after Mpro-mediated cleavage, in live cells. Here, we have engineered a pair of genetically encoded, Bioluminescence Resonance Energy Transfer (BRET)-based sensors for detecting SARS-CoV-2 Mpro proteolytic activity in living host cells as well as in vitro assays. The sensors were generated by sandwiching Mpro N-terminal autocleavage sites, either AVLQSGFR (short) or KTSAVLQSGFRKME (long), in between the mNeonGreen and nanoLuc proteins. Co-expression of the sensor with the Mpro in live cells resulted in its cleavage in a dose- and time-dependent manner while mutation of the critical C145 residue (C145A) in Mpro completely abrogated the sensor cleavage. Importantly, the BRET-based sensors displayed increased sensitivities and specificities as compared to the recently developed FlipGFP-based Mpro sensor. Additionally, the sensors recapitulated the inhibition of Mpro by the well-characterized pharmacological agent GC376. Further, in vitro assays with the BRET-based Mpro sensors revealed a molecular crowding-mediated increase in the rate of Mpro activity and a decrease in the inhibitory potential of GC376. The sensor developed here will find direct utility in studies related to drug discovery targeting the SARS-CoV-2 Mpro and functional genomics application to determine the effect of sequence variation in Mpro.

Environmental correlation and epidemiologic analysis of COVID-19 pandemic in ten regions in five continents.

BACKGROUND: Coronavirus disease-2019 (COVID-19) has caused worldwide health emergencies during the last 6 months of 2020. Within very short time, severe acute respiratory coronavirus-2 (SARS-CoV-2) has infected over 64,516,333 people with 1,493,264 fatalities in 210 countries and regions. Previous studies have reported that environmental factors can affect the viability and transmission of SARS-CoV-2. This study aimed to determine the correlation of environmental factors with COVID-19 pandemic and epidemiology of COVID-19 across nine countries in five continents. METHODS: Both environmental and health data were retrieved from various databases during January 1, 2020 to June 30, 2020. Mean value of environmental factors were calculated for weekly and daily cases and fatalities. Spearman correlation test was conducted. RESULTS: In this study, most of the COVID-19 cases and fatalities were detected from regions (New York, Madrid, Lombardy, London and Sau Paulo) with 7 °C-25 °C mean temperature per day, 3 to 6 mean UV index per day and 14 km/h to 22 km/h mean wind velocity per day. Both cases and fatalities increased significantly after removing lockdown in Bangladesh, India, Brazil and South Africa. Over 50% COVID-19 patients were asymptomatic in every country except Brazil and Australia. Fever (>50%) was the most common symptom followed by cough (45%), tiredness (38%) and sore throat (30%), respectively. In India and Bangladesh over 70% of cases were reported in male. Significant correlation of COVID-19 cases with temperature and UV were detected in London, Lombardy, Madrid, New York and Dhaka. CONCLUSION: This is one of the first cross-country epidemiologic and correlation studies between environmental factors and COVID-19 pandemics. This study will help both local and international health organizations and policy makers to face the COVID-19 challenge.

Exploring the Behavioral Determinants of COVID-19 Vaccine Acceptance among an Urban Population in Bangladesh: Implications for Behavior Change Interventions

BackgroundWhile vaccines ensure individual protection against COVID-19 infection, delay in receipt or refusal of vaccines will have both individual and community impacts. The behavioral factors of vaccine hesitancy or refusal are a crucial dimension that need understanding to implicate appropriate interventions. The aim of this study was to assess the behavioral determinants of COVID-19 vaccine acceptance and to provide recommendations to increase the uptake of COVID-19 vaccines in Bangladesh. MethodsWe employed a Barrier Analysis (BA) approach to examine twelve potential behavioral determinants (drawn from the Health Belief Model and Theory of Reasoned Action [TRA]) of intended vaccine acceptance. We conducted 45 interviews with those who intended to take the vaccine (Acceptors) and another 45 interviews with those who did not have that intention (Non-acceptors). We performed data analysis to find statistically significant differences and to identify which beliefs were most highly associated with acceptance and non-acceptance with COVID-19 vaccines. ResultsCOVID-19 vaccine Acceptors in Dhaka were different from Non-acceptors in terms of many of their beliefs and responses. The behavioral determinants associated with the behavior included perceived social norms, perceived safety of COVID-19 vaccines and trust in them, perceived risk/susceptibility, perceived self-efficacy, perceived positive and negative consequences, perceived action efficacy, perceived severity of COVID-19, access, and perceived divine will. In line with the Health Belief Model, beliefs about the disease itself were highly correlated with vaccine acceptance, although not the only determinant. Other responses of Acceptors provide clues such as providing vaccination through government health facilities, schools, and kiosks, and having vaccinators maintain proper COVID-19 health and safety protocols as to ways to make it easier to boost acceptance. ConclusionAn effective behavior change strategy for COVID-19 vaccines uptake will need to address multiple beliefs and behavioral determinants, reducing barriers and leveraging enablers identified in this study. The national plans on COVID-19 vaccination should adopt culturally and community label acceptable and appropriate evidence-based behavior change interventions strategies to promote high vaccination coverage and acceptance in all societal structures across the country.

Association between body mass index and arsenic methylation in three studies of Bangladeshi adults and adolescents.

BACKGROUND: Water-borne arsenic (As) exposure is a global health problem. Once ingested, inorganic As (iAs) is methylated to mono-methyl (MMA) and dimethyl (DMA) arsenicals via one-carbon metabolism (OCM). People with higher relative percentage of MMA (MMA%) in urine (inefficient As methylation), have been shown to have a higher risk of cardiovascular disease and several cancers but appear to have a lower risk of diabetes and obesity in populations from the US, Mexico, and Taiwan. It is unknown if this opposite pattern with obesity is present in Bangladesh, a country with lower adiposity and higher As exposure in drinking water. OBJECTIVE: To characterize the association between body mass index (BMI) and As methylation in Bangladeshi adults and adolescents participating in the Folic Acid and Creatine Trial (FACT); Folate and Oxidative Stress (FOX) study; and Metals, Arsenic, and Nutrition in Adolescents Study (MANAS). METHODS: Arsenic species (iAs, MMA, DMA) were measured in urine and blood. Height and weight were measured to calculate BMI. The associations between concurrent BMI with urine and blood As species were analyzed using linear regression models, adjusting for nutrients involved in OCM such as choline. In FACT, we also evaluated the prospective association between weight change and As species. RESULTS: Mean BMIs were 19.2/20.4, 19.8/21.0, and 17.7/18.7 kg/m2 in males/females in FACT, FOX, and MANAS, respectively. BMI was associated with As species in female but not in male participants. In females, after adjustment for total urine As, age, and plasma folate, the adjusted mean differences (95% confidence) in urinary MMA% and DMA% for a 5 kg/m2 difference in BMI were -1.21 (-1.96, -0.45) and 2.47 (1.13, 3.81), respectively in FACT, -0.66 (-1.56, 0.25) and 1.43 (-0.23, 3.09) in FOX, and -0.59 (-1.19, 0.02) and 1.58 (-0.15, 3.30) in MANAS. The associations were attenuated after adjustment for choline. Similar associations were observed with blood As species. In FACT, a 1-kg of weight increase over 2 to 10 (mean 5.4) years in males/females was prospectively associated with mean DMA% that was 0.16%/0.19% higher. DISCUSSION: BMI was negatively associated with MMA% and positively associated with %DMA in females but not males in Bangladesh; associations were attenuated after plasma choline adjustment. These findings may be related to the role of body fat on estrogen levels that can influence one-carbon metabolism, e.g. by increasing choline synthesis. Research is needed to determine whether the associations between BMI and As species are causal and their influence on As-related health outcomes.

Knowledge, attitude, and practices regarding COVID-19: A study on workers from a food industry in Bangladesh.

While people around the world are terrified of the global pandemic coronavirus disease 2019 (COVID-19) and are dying for a permanent solution, undertaking preventive safety measures are said to be the most effective way to stay away from it. Peoples adherences to these measures are broadly dependent on their knowledge, attitude, and practices (KAP). People working in the food industries must be extra cautious during this time because they are in close proximity to consumable items. The present study was designed to evaluate food handlers knowledge, attitude, and practices regarding COVID-19 in different food industries in Bangladesh. A number of 400 food handlers from 15 food industries took part in this online-based study. The information was collected from the participants through a questionnaire prepared in Google form. With a correct response rate of about 90% on average (knowledge 89.7%, attitude 93%, practices 88.2%), the participants showed an acceptable of KAP regarding COVID-19. Education and working experiences had a significant association with the total KAP scores (p < 0.05). The findings may assist public health professionals and practitioners in developing targeted strategies for implementing such studies in other industrial sectors and taking appropriate measures based on the KAP studies.

Deep neural networks capture texture sensitivity in V2.

Deep convolutional neural networks (CNNs) trained on visual objects have shown intriguing ability to predict some response properties of visual cortical neurons. However, the factors (e.g., if the model is trained or not, receptive field size) and computations (e.g., convolution, rectification, pooling, normalization) that give rise to such ability, at what level, and the role of intermediate processing stages in explaining changes that develop across areas of the cortical hierarchy are poorly understood. We focused on the sensitivity to textures as a paradigmatic example, since recent neurophysiology experiments provide rich data pointing to texture sensitivity in secondary (but not primary) visual cortex (V2). We initially explored the CNN without any fitting to the neural data and found that the first two layers of the CNN showed qualitative correspondence to the first two cortical areas in terms of texture sensitivity. We therefore developed a quantitative approach to select a population of CNN model neurons that best fits the brain neural recordings. We found that the CNN could develop compatibility to secondary cortex in the second layer following rectification and that this was improved following pooling but only mildly influenced by the local normalization operation. Higher layers of the CNN could further, though modestly, improve the compatibility with the V2 data. The compatibility was reduced when incorporating random rather than learned weights. Our results show that the CNN class of model is effective for capturing changes that develop across early areas of cortex, and has the potential to help identify the computations that give rise to hierarchical processing in the brain (code is available in GitHub).

The Aging Imageomics Study: rationale, design and baseline characteristics of the study population.

Biomarkers of aging are urgently needed to identify individuals at high risk of developing age-associated disease or disability. Growing evidence from population-based studies points to whole-body magnetic resonance imaging's (MRI) enormous potential for quantifying subclinical disease burden and for assessing changes that occur with aging in all organ systems. The Aging Imageomics Study aims to identify biomarkers of human aging by analyzing imaging, biopsychosocial, cardiovascular, metabolomic, lipidomic, and microbiome variables. This study recruited 1030 participants aged ≥50 years (mean 67, range 50-96 years) that underwent structural and functional MRI to evaluate the brain, large blood vessels, heart, abdominal organs, fat, spine, musculoskeletal system and ultrasonography to assess carotid intima-media thickness and plaques. Patients were notified of incidental findings detected by a certified radiologist when necessary. Extensive data were also collected on anthropometrics, demographics, health history, neuropsychology, employment, income, family status, exposure to air pollution and cardiovascular status. In addition, several types of samples were gathered to allow for microbiome, metabolomic and lipidomic profiling. Using big data techniques to analyze all the data points from biological phenotyping together with health records and lifestyle measures, we aim to cultivate a deeper understanding about various biological factors (and combinations thereof) that underlie healthy and unhealthy aging.

Epitope-Based Peptide Vaccine Against Severe Acute Respiratory Syndrome-Coronavirus-2 Nucleocapsid Protein: An in silico Approach

With an increasing fatality rate, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has emerged as a promising threat to human health worldwide. SARS-CoV-2 is a member of the Coronaviridae family, which is transmitted from animal to human and because of being contagious, further it transmitted human to human. Recently, the World Health Organization (WHO) has announced the infectious disease caused by SARS-CoV-2, which is known as coronavirus disease-2019 (COVID-2019) as a global pandemic. But, no specific medications are available for the treatment of COVID-19 so far. As a corollary, there is a need for a potential vaccine to impede the progression of the disease. Lately, it has been documented that the nucleocapsid (N) protein of SARS-CoV-2 is responsible for viral replication as well as interferes with host immune responses. We have comparatively analyzed the sequences of N protein of SARS-CoV-2 for the identification of core attributes and analyzed the ancestry through phylogenetic analysis. Subsequently, we have predicted the most immunogenic epitope for T-cell as well as B-cell. Importantly, our investigation mainly focused on major histocompatibility complex (MHC) class I potential peptides and NTASWFTAL interacted with most human leukocyte antigen (HLA) that are encoded by MHC class I molecules. Further, molecular docking analysis unveiled that NTASWFTAL possessed a greater affinity towards HLA and also available in a greater range of the population. Our study provides a consolidated base for vaccine design and we hope that this computational analysis will pave the way for designing novel vaccine candidates.

Molecular and Epidemiologic Analysis of Diarrheal Pathogens in Children With Acute Gastroenteritis in Bangladesh During 2014-2019.

BACKGROUND: Diarrheal disease is one of the leading causes of childhood morbidity and mortality in the 21st century in developing countries. Mainly infants and young children develop diarrheal diseases. This study aims to determine the incidence of diarrheal pathogens in children in Bangladesh. METHODS: During 2014 to 2019, 387 fecal specimens were collected from children with diarrhea in Bangladesh. Bacterial pathogens were detected by conventional bacteriologic, biochemical and molecular sequence analysis methods. DNA virus and RNA virus (diarrheal viruses) were detected using polymerase chain reaction and reverse transcriptase polymerase chain reaction, respectively and confirmed by molecular sequence analysis. RESULTS: Bacterial infections were detected in 39.27% (152 of 387) of the stool samples. Escherichia coli was the most prevalent (17.3%) followed by Vibrio cholerae (13.5%), Salmonella spp. (4.9%) and Shigella spp. (3.6%). From 387 fecal specimens tested, 42.4% (164 of 387) were positive for viral infections. Rotavirus was the most prevalent (26.3%), followed by adenovirus (5.7%), norovirus (5.4%) and human bocavirus (4.9%). Dual infection between rotavirus and E. coli accounted for the largest portion of coinfection (48%). Diarrhea (77%) and abdominal pain (65%) were most common followed by vomiting (63%), fever (43%) and dehydration (39%). E. coli and V. cholerae were most resistant against ciprofloxacin (62.7%) and tetracycline (88.5%). qnrA and sul4 resistance genes were isolated from these pathogens. CONCLUSIONS: Data from this study underline the high incidence of diarrheal pathogens and presence of antibiotics resistance genes in a pediatric population in Bangladesh.