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Aim: This study investigates the altered expression and CpG methylation patterns of histone demethylase KDM8 in hepatocellular carcinoma (HCC), aiming to uncover insights and promising diagnostics biomarkers. Materials & methods: Leveraging TCGA-LIHC multi-omics data, we employed R/Bioconductor libraries and Cytoscape to analyze and construct a gene correlation network, and LASSO regression to develop an HCC-predictive model. Results: In HCC, KDM8 downregulation is correlated with CpGs hypermethylation. Differential gene correlation analysis unveiled a liver carcinoma-associated network marked by increased cell division and compromised liver-specific functions. The LASSO regression identified a highly accurate HCC prediction signature, prominently featuring CpG methylation at cg02871891. Conclusion: Our study uncovers CpG hypermethylation at cg02871891, possibly influencing KDM8 downregulation in HCC, suggesting these as promising biomarkers and targets.
Changes in gene function can play a role in causing cancer. In this study, we looked at how a specific gene called KDM8 behaves in liver cancer. By analyzing a large set of liver cancer samples, we investigated how gene interactions are different in this disease and if they can help predict liver cancer risk. Our results show that the KDM8 gene is less active, and its DNA gets chemically modified more often in liver cancer. We also found a group of genes and DNA changes, which are linked to the disease. Using this information, we identified 16 important markers and built a computer model that can accurately predict liver cancer. We found that DNA methylation at a specific spot called cg02871891 is especially important for predicting liver cancer. Overall, our study suggests that high levels of DNA methylation may lead to reduced KDM8 activity in liver cancer, which could be important for future research and better diagnostic tools.
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The Nipah virus (NiV) belongs to the Henipavirus genus is a serious public health concern causing numerous outbreaks with higher fatality rate. Unfortunately, there is no effective medication available for NiV. To investigate possible inhibitors of NiV infection, we used in silico techniques to discover treatment candidates in this work. As there are not any approved treatments for NiV infection, the NiV-enveloped attachment glycoprotein was set as target for our study, which is responsible for binding to and entering host cells. Our in silico drug design approach included molecular docking, post-docking molecular mechanism generalised born surface area (MM-GBSA), absorption, distribution, metabolism, excretion/toxicity (ADME/T), and molecular dynamics (MD) simulations. We retrieved 418 phytochemicals associated with the neem plant (Azadirachta indica) from the IMPPAT database, and molecular docking was used to ascertain the compounds' binding strength. The top 3 phytochemicals with binding affinities of -7.118, -7.074, and -6.894 kcal/mol for CIDs 5280343, 9064, and 5280863, respectively, were selected for additional study based on molecular docking. The post-docking MM-GBSA of those 3 compounds was -47.56, -47.3, and -43.15 kcal/mol, respectively. As evidence of their efficacy and safety, all the chosen drugs had favorable toxicological and pharmacokinetic (Pk) qualities. We also performed MD simulations to confirm the stability of the ligand-protein complex structures and determine whether the selected compounds are stable at the protein binding site. All 3 phytochemicals, Quercetin (CID: 5280343), Cianidanol (CID: 9064), and Kaempferol (CID: 5280863), appeared to have outstanding binding stability to the target protein than control ribavirin, according to the molecular docking, MM-GBSA, and MD simulation outcomes. Overall, this work offers a viable approach to developing novel medications for treating NiV infection.
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BACKGROUND: Endometriosis is a disease among women of reproductive age, which causes several health problems, such as dysmenorrhea, dyspareunia, and subfertility. In addition, it increases psychological stress and often results in marital disharmony. Similarly, migraine is more frequent among this group of women. Several studies have shown an association between endometriosis and migraine among groups of populations completely different from Bangladesh. OBJECTIVE: This study aimed to identify the association between endometriosis and migraine among the Bangladeshi population. STUDY DESIGN: This nonrandomized case-control study was conducted with cases of endometriosis and controls without endometriosis who were confirmed by laparoscopy or laparotomy. Among the study participants, cases of migraine in 1 group of respondents who were already diagnosed as patients of migraine were identified, and the others with complaints of headaches were further confirmed by a medicine specialist. Patients were recruited from the Department of Obstetrics and Gynecology at the Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders General Hospital and Ibrahim Medical College. The study was approved by the ethical review committee of the Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders General Hospital. Multivariate logistic regression was used to identify the association between endometriosis and migraine using odds ratios and 95% confidence intervals. RESULTS: Of 1496 patients who underwent laparoscopy or laparotomy during the study period, the frequency of endometriosis was found to be 12.7%. A total of 190 patients with confirmed endometriosis cases and an equal number of controls without endometriosis were enrolled, maintaining the age distribution of the controls similar to that of the cases. Compared with controls, the distribution of age, body mass index, education, and marital status of the patients with endometriosis were similar. The average ages of respondents were 30.6 years in both the case and control groups. Regarding occupation, cases included more students than controls (12% vs 0%, respectively). The odds of suffering from dysmenorrhea and dyspareunia among the cases were 3.3 (95% confidence interval, 2.66-4.15; P<.001) and 9.5 (95% confidence interval, 5.3-17.9; P<.001) times higher than that of controls, respectively. In addition, the odds of menstrual irregularity was 60% lower among the cases than among controls (odds ratio, 0.4; 95% confidence interval, 0.24-0.64; P<.001). No significant difference was observed in having primary subfertility and secondary subfertility among the 2 groups of respondents. Univariate regression analysis showed that patients with endometriosis have 6.13 times higher odds (95% confidence interval, 2.50-18.40; P<.001) of having a migraine and 2.00 times higher odds (95% confidence interval, 1.2-3.2; P=.01) of having a headache than controls. Furthermore, the age- and body mass index-adjusted multivariate model showed that patients with endometriosis have 5.4 times higher odds of having migraine than patients without endometriosis (95% confidence interval, 2.11-16.4; P<.001). In addition, the higher the age of reproductive-age women, the higher the odds of having migraine. A 1-year increase in age increases the odds of having migraine by 23% (odds ratio, 1.23; 95% confidence interval, 1.13-1.16; P<.001). CONCLUSION: Our results support the association between endometriosis and migraine among the Bangladeshi population, which is similar to relevant studies conducted in other geographic locations. The groups of physicians who treat patients suffering from the 2 diseases, endometriosis and migraine, should keep this interrelationship in mind to ensure a better quality of life for the patient.
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Widespread contamination by heavy metals (HMs) and dyes poses a major health risk to people and ecosystems requiring effective treatment. In this work, rice husk (RH) and shrimp shells were extracted to obtain amorphous silica and chitosan, respectively, which were utilized to produce nano-chitosan-coated silica (NCCS). To ensure the stability of the nanoparticles, silica was freeze-dried after being coated with nano-chitosan. Functional groups (-NH2, -OH, P]O) from chitosan nanoparticles (CNPs) were introduced to the surface of silica during this process. Dyes such as brilliant green (BG), methylene blue (MB) and reactive brown (RB) as well as HMs (Cr6+, Pb2+, Cd2+, Ni2+) were removed by adsorbents. CNPs showed the highest adsorption capacity for RB (59.52 mg/g) among dyes and Cr6+ (42.55 mg/g) among HMs. CNPs showed the highest adsorption capacity for HMs among different adsorbents. Although NCCS and CNPs showed similar adsorption capabilities for HMs and dyes, NCCS showed the best stability. The adsorption performance decreased as RB > Cr6+ > MB > BG > Pb2+ > Cd2+ > Ni2+. The adsorption reactions followed both pseudo-first-order and second-order kinetics, and was spontaneous from thermodynamic analysis. In summary, the waste-derived adsorbents demonstrated excellent potential for removing HMs and dyes from water, while supporting effective management solid waste.
Subject(s)
Chitosan , Metals, Heavy , Oryza , Water Pollutants, Chemical , Humans , Cadmium , Coloring Agents , Water , Ecosystem , Lead , Silicon Dioxide , Adsorption , Kinetics , Hydrogen-Ion ConcentrationABSTRACT
BACKGROUND: Antimicrobial resistance poses a huge risk to human health worldwide, while Bangladesh is confronting the most severe challenge between the food supply and the huge consumption of antibiotics annually. More importantly, probiotics containing Bacillus spp. are claimed to be an alternative to antimicrobial stewardship programs. However, their antibiotic resistance remains elusive. Thus, we employed the antimicrobial susceptibility test and PCR to assess the prevalence of resistance, including multidrug resistance (MDR) and resito-genotyping of isolated Bacillus spp. RESULTS: The phenotypic profile showed that Bacillus spp. were 100% sensitive to gentamicin (2 µg/mL), whereas lowered sensitivity to levofloxacin (67.8%, 0.5-1 µg/mL), ciprofloxacin (62.3%, 0.5-1 µg/mL), clindamycin (52.2%, 0.25-0.5 µg/mL), amoxicillin-clavulanic acid (37.6%, 0.06 µg/mL), azithromycin (33.4%, 1-2 µg/mL), tetracycline (25.6%, 2-4 µg/mL), nitrofurantoin (21.1%, 16-32 µg/mL), co-trimoxazole (19.2%, 2 µg/mL), and erythromycin (18.8%, 0.25-0.5 µg/mL). The strains were completely resistant to penicillin, amoxicillin-clavulanic acid, cefixime, ceftriaxone, vancomycin, and co-trimoxazole, and a species-specific trend was seen in both phenotypic and genotypic resistance patterns. Genotypic resistance indicated prevalence of the bla1 (71.5%), tetA (33%), erm1 (27%), blaTEM (13.1%), blaCTX-M-1/blaCTX-M-2 /sul1 (10.1%), blaSHV (9.6%), and qnrS (4.1%) genes. The ß-lactamase resistance gene bla1 was found in all penicillin-resistant (MIC ≥ 32 µg/mL) Bacillus spp. One hundred ninety-one isolates (89.6%) were MDR, with 100% from diarrhea, 90.3% from food, and 88.7% from animal feed. CONCLUSION: Based on the MIC value and profile analysis of antibiotic resistance genes, this is the first study that Bacillus spp. antimicrobial susceptibilities have been identified in Bangladesh, and our study will shed light on the adverse effects of feed-borne Bacillus spp. emerging from animal feed to the food chain. A comprehensive investigation is urgently needed by policymakers on tolerance limits and harmful effects in the animal industry.
Subject(s)
Bacillus , Humans , Animals , Bacillus/genetics , Trimethoprim, Sulfamethoxazole Drug Combination , Amoxicillin-Potassium Clavulanate Combination , Bangladesh/epidemiology , Anti-Bacterial Agents/pharmacology , Diarrhea , Penicillins , Animal Feed , Microbial Sensitivity TestsABSTRACT
Brucellosis is a zoonotic disease, caused by some species within the Brucella genus. The primary and secondary objectives of this cross-sectional study were to determine the seroprevalence of Brucella antibodies in humans and cows and identify risk factors for exposure to Brucella spp. among people in Shahjadpur sub-district, Bangladesh. Twenty-five villages were randomly selected from the 303 milk-producing villages in the sub-district. We randomly selected 5% of the total households from each village. At each household, we collected demographic information and history of potential exposure to Brucella spp. in humans. In addition, we collected serum from household participants and serum and milk from cattle and tested to detect antibodies to Brucella sp. Univariate analysis was performed to detect associations between seropositivity and demographics, risk factors, and behaviors in households. We enrolled 647 households, 1313 humans, and 698 cows. Brucella antibodies were detected in sera from 27 household participants (2.1%, 95% confidence interval [95%CI]: 1.2-2.9%). Eleven (1.6%, 95%CI 0.6-2.4%) cows had detectable Brucella antibodies in either milk or serum. About half (53%) of the 698 cows exhibited more than one reproductive problem within the past year; of these, seven (2%) had Brucella antibodies. Households with seropositive individuals more frequently reported owning cattle (78% vs. 32%, P < 0.001). Despite a low prevalence of Brucella seropositivity in the study, the public health importance of brucellosis cannot be ruled out. Further studies would help define Brucella prevalence and risk factors in this region and nationally.
Subject(s)
Brucella , Brucellosis , Female , Humans , Animals , Cattle , Milk , Cross-Sectional Studies , Seroepidemiologic Studies , Bangladesh/epidemiology , Brucellosis/epidemiology , Brucellosis/veterinary , Antibodies, Bacterial , Risk FactorsABSTRACT
Curcuma longa L. (turmeric), Beta vulgaris L. (beetroot), and Daucus carota L. (carrot) grown in Bangladesh were analyzed for nutritional and phytochemical contents to reveal their comparative nutritional compositions and antiradical properties. Ash, protein, and carbohydrate content were significantly preeminent in beetroot as compared to others. Whereas fat content was found to be high in turmeric, carrots contained a great percentage of crude fiber. Beetroot was shown to have much greater potassium, calcium, and iron levels than others. Regarding amino acids, glutamic acid was found to be greater in beetroot and carrot whereas turmeric had significantly high aspartic acid content. Leucine had the highest concentration among essential amino acids in these three samples. Total antioxidant activity, total flavonoids, and phenolic contents in the methanolic extract of turmeric were found to be substantially higher than in beetroot and carrot. Furthermore, the extract of turmeric (IC50 value: 13.46 µg/mL) scavenged 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) free radicals considerably to a greater extent than beetroot (IC50 value: 380.61 µg/mL) and carrot (IC50 value: 1252.85 µg/mL). A positive correlation was found between the phytochemical contents and antiradical activity. The information from this study will help to find the potential ingredients from these plants for functional food.
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Nanotechnology has become a cutting-edge field of research that has emerged as an interdisciplinary research area and contributes to almost every field of science. With the increasing demand for sustainable greener products, attention has recently been focused on green nanotechnology. This study manifested the aptitude of Leea macrophylla (LM) leaf extract, fortified with phytochemicals, to biosynthesize silver nanoparticles (AgNPs) for the first time. As soon as the AgNPs were biosynthesized, they immediately changed color, and the distinctive surface plasmon resonance (SPR) occurred at 420 nm in the Ultraviolet-Visible spectrum, proving that the biosynthesis had been successful. Fourier Transform Infrared Spectroscopy (FTIR) was used to examine the phytochemicals present in the LM leaf extract, those are accountable for the formation and stabilization of AgNPs. The Transmission Electron Microscope (TEM) revealed the formation of quasi spherical silver nanoparticles with an average diameter of 22.77 nm. Synthesized nanoparticles were further characterized by X-ray diffraction (XRD), Field Emission Scanning Electron microscope (FESEM), Energy Dispersive X-ray (EDX), Dynamic Light Scattering (DLS) and Thermogravimetric analysis (TGA). The production of AgNPs with high metal content from LM leaf extract exhibited encouraging results. The LM leaf extract mediated silver nanoparticles evinced significant antibacterial and catalytic activities. The cytotoxicity effects of biosynthesized AgNPs were tested on brine shrimps.
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[This corrects the article DOI: 10.3389/fpubh.2022.985445.].
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Respiratory syncytial virus (RSV) is a common respiratory pathogen that causes mild cold-like symptoms and severe lower respiratory tract infections, causing hospitalizations in children, the elderly and immunocompromised individuals. Due to genetic variability, this virus causes life-threatening pneumonia and bronchiolitis in young infants. Thus, we examined 3600 whole genome sequences submitted to GISAID by 31 December 2022 to examine the genetic variability of RSV. While RSVA and RSVB coexist throughout RSV seasons, RSVA is more prevalent, fatal, and epidemic-prone in several countries, including the United States, the United Kingdom, Australia, and China. Additionally, the virus's attachment glycoprotein and fusion protein were highly mutated, with RSVA having higher Shannon entropy than RSVB. The genetic makeup of these viruses contributes significantly to their prevalence and epidemic potential. Several strain-specific SNPs co-occurred with specific haplotypes of RSVA and RSVB, followed by different haplotypes of the viruses. RSVA and RSVB have the highest linkage probability at loci T12844A/T3483C and G13959T/C2198T, respectively. The results indicate that specific haplotypes and SNPs may significantly affect their spread. Overall, this analysis presents a promising strategy for tracking the evolving epidemic situation and genetic variants of RSV, which could aid in developing effective control, prophylactic, and treatment strategies.
Subject(s)
Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Child , Aged , Infant , Humans , Genome-Wide Association Study , Respiratory Syncytial Virus, Human/genetics , Australia/epidemiology , ChinaABSTRACT
Genomes may now be sequenced in a matter of weeks, leading to an influx of "hypothetical" proteins (HP) whose activities remain a mystery in GenBank. The information included inside these genes has quickly grown in prominence. Thus, we selected to look closely at the structure and function of an HP (AFF25514.1; 246 residues) from Pasteurella multocida (PM) subsp. multocida str. HN06. Possible insights into bacterial adaptation to new environments and metabolic changes might be gained by studying the functions of this protein. The PM HN06 2293 gene encodes an alkaline cytoplasmic protein with a molecular weight of 28352.60 Da, an isoelectric point (pI) of 9.18, and an overall average hydropathicity of around -0.565. One of its functional domains, tRNA (adenine (37)-N6)-methyltransferase TrmO, is a S-adenosylmethionine (SAM)-dependent methyltransferase (MTase), suggesting that it belongs to the Class VIII SAM-dependent MTase family. The tertiary structures represented by HHpred and I-TASSER models were found to be flawless. We predicted the model's active site using the Computed Atlas of Surface Topography of Proteins (CASTp) and FTSite servers, and then displayed it in 3 dimensional (3D) using PyMOL and BIOVIA Discovery Studio. Based on molecular docking (MD) results, we know that HP interacts with SAM and S-adenosylhomocysteine (SAH), 2 crucial metabolites in the tRNA methylation process, with binding affinities of 7.4 and 7.5 kcal/mol, respectively. Molecular dynamic simulations (MDS) of the docked complex, which included only modest structural adjustments, corroborated the strong binding affinity of SAM and SAH to the HP. Evidence for HP's possible role as an SAM-dependent MTase was therefore given by the findings of Multiple sequence alignment (MSA), MD, and molecular dynamic modeling. These in silico data suggest that the investigated HP might be used as a useful adjunct in the investigation of Pasteurella infections and the development of drugs to treat zoonotic pasteurellosis.
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Avirulent halotolerant plant growth-promoting rhizobacteria (HPGPR) located on the roots' periphery can reduce abiotic stressors (such as salinity and drought), enhance plant productivity. Salinity poses a significant challenge for growing agricultural products, like rice, in the coastal regions. It is crucial to enhance production because of limited arable land and the high growth rate of the population. This study targeted to identify HPGPR from legume root nodules and assessed their effects on rice plants experiencing salt stress in coastal regions of Bangladesh. Based on the culture morphology, biochemical, salt, pH, and temperature tolerance traits, sixteen bacteria were isolated from the root nodules of leguminous plants (Common bean, Yardlong bean, Dhaincha, and Shameplant). All the bacterial strains can tolerate 3 % salt concentration, and capable to survive at the highest 45 °C temperature and pH 11 (without isolate 1). Three preeminent bacteria, Agrobacterium tumefaciens (B1), Bacillus subtilis (B2), and Lysinibacillus fusiformis (B3) were specified through morpho-biochemical and molecular (16S rRNA gene sequence) exploration for inoculation. To assess the plant growth-promoting activities, germination tests are applied where bacterial inoculation increased germination in saline and non-saline conditions. Control group (C) showed 89.47 % and bacterial treated groups (C + B1, C + B2, and C + B3) 95 %, 90 %, and 75 % germination after 2 days of inoculation. In (1 % NaCl) saline condition control group revealed 40 % whereas three groups with bacteria showed 60 %, 40 %, and 70 % germination after 3 days, which increased 70 %, 90 %, 85 %, and 95 % respectively after 4 days of inoculation. The HPGPR significantly improved plant development metrics such as root length, shoot length, fresh and arid biomass yield, chlorophyll content, etc. Our results suggest that the salt-resistant bacteria (Halotolerant) have a great potential role in recuperating plant growth and would be cost-effective as a bio-inoculant in saline conditions to be used as a prospective bio-fertilizer for rice production. These findings indicate that the HPGPR has a substantially promising function in reviving plant development in an eco-friendly manner.
Subject(s)
Oryza , Seedlings , Oryza/genetics , RNA, Ribosomal, 16S/genetics , Prospective Studies , Salt-Tolerant Plants/genetics , Salt Stress , Bacteria , Salinity , Plant Roots/microbiologyABSTRACT
Humans frequently contract urinary tract infections (UTIs), which can be brought on by uropathogens (UPs) that are multi-drug resistant. Treatment for UTIs brought on by pathogenic UPs that produce extended-spectrum lactamases (ESBLs) is more costly and potentially fatal. As a result, the objective of this study was to use culture, biochemical, and 16S rRNA sequencing to identify and characterize UPs isolated from outpatients in Noakhali, Bangladesh, who had symptoms of UTIs. ESBL gene identification and quinolone resistance gene typing were then performed on the isolates using polymerase chain reaction (PCR). Throughout the trial's 8-month duration, 152 (76%) of 200 urine samples were positive for the presence of UPs. The overall number of UPs recovered was 210, with 39 individuals having multiple UPs present in their samples. Among all of the isolates, Escherichia coli (45.24%, 95/210; 95% confidence interval (CI): 35.15-57.60%), Enterobacter spp. (24.76%, 52/210; CI: 19.15-35.77%), Klebsiella spp. (20.95%; 44/210; CI: 15.15-30.20%), and Providencia spp. (9.05%; 19/210; CI: 4.95-19.25%) were the four most prevalent bacteria found in the isolates. The UPs displayed a very high level of resistance to piperacillin 96.92% (126/130), ampicillin 90% (117/130), nalidixic acid 77.69% (101/130), cefazolin 70% (91/130), amoxicillin 50% (55/130), cefazolin 42.31% (55/130), nitrofurantoin 43.08% (56/130), and ciprofloxacin 33.08% (43/130), whereas resistance to netilmicin (3.85%), amikacin (4.62%), and imipenem (9.23%) was low. Individually, every species of E. coli and Providencia spp. showed greater ampicillin, amikacin, cefazolin, cefazolin, and nalidixic acid resistance than the others. The bivariate results indicate several antibiotic pairings, and isolates had meaningful associations. All MDR isolates were subjected to PCR, which revealed that blaCTX-M-15 genes predominated among the isolates, followed by the blaTEM class (37%). Isolates also had the qnrS, aac-6´-Ib-cr, and gyrA genes. The findings provide worrying indications of a major expansion of MDR isolates in the study locations, particularly the epidemiological balCTX-M 15, with the potential for the transmission of multi-drug-resistant UP strains in the population.
Subject(s)
Escherichia coli Infections , Quinolones , Urinary Tract Infections , Humans , Escherichia coli , Anti-Bacterial Agents/pharmacology , Escherichia coli Infections/microbiology , Quinolones/pharmacology , Cefazolin , Amikacin , Nalidixic Acid , Bangladesh/epidemiology , RNA, Ribosomal, 16S/genetics , Drug Resistance, Multiple, Bacterial/genetics , beta-Lactamases/genetics , Drug Resistance, Bacterial , Urinary Tract Infections/microbiology , Ampicillin , Microbial Sensitivity TestsABSTRACT
The ongoing COVID-19 contagious disease caused by SARS-CoV-2 has disrupted global public health, businesses, and economies due to widespread infection, with 676.41 million confirmed cases and 6.77 million deaths in 231 countries as of February 07, 2023. To control the rapid spread of SARS-CoV-2, it is crucial to determine the potential determinants such as meteorological factors and their roles. This study examines how COVID-19 cases and deaths changed over time while assessing meteorological characteristics that could impact these disparities from the onset of the pandemic. We used data spanning two years across all eight administrative divisions, this is the first of its kind--showing a connection between meteorological conditions, vaccination, and COVID-19 incidences in Bangladesh. We further employed several techniques including Simple Exponential Smoothing (SES), Auto-Regressive Integrated Moving Average (ARIMA), Auto-Regressive Integrated Moving Average with explanatory variables (ARIMAX), and Automatic forecasting time-series model (Prophet). We further analyzed the effects of COVID-19 vaccination on daily cases and deaths. Data on COVID-19 cases collected include eight administrative divisions of Bangladesh spanning March 8, 2020, to January 31, 2023, from available online servers. The meteorological data include rainfall (mm), relative humidity (%), average temperature (°C), surface pressure (kPa), dew point (°C), and maximum wind speed (m/s). The observed wind speed and surface pressure show a significant negative impact on COVID-19 cases (-0.89, 95% confidence interval (CI): 1.62 to -0.21) and (-1.31, 95%CI: 2.32 to -0.29), respectively. Similarly, the observed wind speed and surface pressure show a significant negative impact on COVID-19 deaths (-0.87, 95% CI: 1.54 to -0.21) and (-3.11, 95%CI: 4.44 to -1.25), respectively. The impact of meteorological factors is almost similar when vaccination information is included in the model. However, the impact of vaccination in both cases and deaths model is significantly negative (for cases: 1.19, 95%CI: 2.35 to -0.38 and for deaths: 1.55, 95%CI: 2.88 to -0.43). Accordingly, vaccination effectively reduces the number of new COVID-19 cases and fatalities in Bangladesh. Thus, these results could assist future researchers and policymakers in the assessment of pandemics, by making thorough efforts that account for COVID-19 vaccinations and meteorological conditions.
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Efficient 13C hyperpolarization of ketoisocaproate is demonstrated in natural isotopic abundance and [1-13C]enriched forms via SABRE-SHEATH (Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei). Parahydrogen, as the source of nuclear spin order, and ketoisocaproate undergo simultaneous chemical exchange with an Ir-IMes-based hexacoordinate complex in CD3OD. SABRE-SHEATH enables spontaneous polarization transfer from parahydrogen-derived hydrides to the 13C nucleus of transiently bound ketoisocaproate. 13C polarization values of up to 18% are achieved at the 1-13C site in 1 min in the liquid state at 30 mM substrate concentration. The efficient polarization build-up becomes possible due to favorable relaxation dynamics. Specifically, the exponential build-up time constant (14.3 ± 0.6 s) is substantially lower than the corresponding polarization decay time constant (22.8 ± 1.2 s) at the optimum polarization transfer field (0.4 microtesla) and temperature (10 °C). The experiments with natural abundance ketoisocaproate revealed polarization level on the 13C-2 site of less than 1%-i.e., one order of magnitude lower than that of the 1-13C site-which is only partially due to more-efficient relaxation dynamics in sub-microtesla fields. We rationalize the overall much lower 13C-2 polarization efficiency in part by less favorable catalyst-binding dynamics of the C-2 site. Pilot SABRE experiments at pH 4.0 (acidified sample) versus pH 6.1 (unaltered sodium [1-13C]ketoisocaproate) reveal substantial modulation of SABRE-SHEATH processes by pH, warranting future systematic pH titration studies of ketoisocaproate, as well as other structurally similar ketocarboxylate motifs including pyruvate and alpha-ketoglutarate, with the overarching goal of maximizing 13C polarization levels in these potent molecular probes. Finally, we also report on the pilot post-mortem use of HP [1-13C]ketoisocaproate in a euthanized mouse, demonstrating that SABRE-hyperpolarized 13C contrast agents hold promise for future metabolic studies.
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Wastewater based epidemiology (WBE) is an important tool to fight against COVID-19 as it provides insights into the health status of the targeted population from a small single house to a large municipality in a cost-effective, rapid, and non-invasive way. The implementation of wastewater based surveillance (WBS) could reduce the burden on the public health system, management of pandemics, help to make informed decisions, and protect public health. In this study, a house with COVID-19 patients was targeted for monitoring the prevalence of SARS-CoV-2 genetic markers in wastewater samples (WS) with clinical specimens (CS) for a period of 30 days. RT-qPCR technique was employed to target nonstructural (ORF1ab) and structural-nucleocapsid (N) protein genes of SARS-CoV-2, according to a validated experimental protocol. Physiological, environmental, and biological parameters were also measured following the American Public Health Association (APHA) standard protocols. SARS-CoV-2 viral shedding in wastewater peaked when the highest number of COVID-19 cases were clinically diagnosed. Throughout the study period, 7450 to 23,000 gene copies/1000 mL were detected, where we identified 47 % (57/120) positive samples from WS and 35 % (128/360) from CS. When the COVID-19 patient number was the lowest (2), the highest CT value (39.4; i.e., lowest copy number) was identified from WS. On the other hand, when the COVID-19 patients were the highest (6), the lowest CT value (25.2 i.e., highest copy numbers) was obtained from WS. An advance signal of increased SARS-CoV-2 viral load from the COVID-19 patient was found in WS earlier than in the CS. Using customized primer sets in a traditional PCR approach, we confirmed that all SARS-CoV-2 variants identified in both CS and WS were Delta variants (B.1.617.2). To our knowledge, this is the first follow-up study to determine a temporal relationship between COVID-19 patients and their discharge of SARS-CoV-2 RNA genetic markers in wastewater from a single house including all family members for clinical sampling from a developing country (Bangladesh), where a proper sewage system is lacking. The salient findings of the study indicate that monitoring the genetic markers of the SARS-CoV-2 virus in wastewater could identify COVID-19 cases, which reduces the burden on the public health system during COVID-19 pandemics.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/epidemiology , Follow-Up Studies , Wastewater , Genetic Markers , RNA, ViralABSTRACT
Stress has been defined in many ways as a state of psychological arousal that results when the external demand is beyond what one can cope with. Stress is caused by various factors called stressors. Medical students are subjected to different kinds of stressors, such as pressure of academics with obligation to succeed, an uncertain future and difficulties of integrating into the system and different teaching protocols, which may affect their learning ability and performance. Stress has a great impact on brain mainly in the form of impaired memory and on cardiovascular function in the form of increased heart rate and blood pressure. The study was planned to assess the effects of examination induced stress on memory and blood pressure. The study was longitudinal in nature conducted at Department of Physiology, Santosh Medical College, Ghaziabad, India. Initially 100 subjects were selected from 17-24 years of age group then all the subjects were divided into two groups of 'slow-learners' and 'fast-learners' based upon their past academic performances. Readings were taken at two stages of academic year, 05 months before pre-prof examination and 03 days before pre-prof examination. Blood Pressure were measured and the memory assessments were done by using 10 subtests of PGI memory scale. We found a significant increase in stress level 3 days before the examination, compared to 5 months before the examination which in turn affected both blood pressure and memory functions. But, slow-learners were affected more compared to fast-learners.
ABSTRACT
The epidermal growth factor receptor (EGFR) plays a crucial role in regulating cellular growth and survival, and its dysregulation is implicated in various cancers, making it a prime target for cancer therapy. Natural compounds known as catechins have garnered attention as promising anticancer agents. These compounds exert their anticancer effects through diverse mechanisms, primarily by inhibiting receptor tyrosine kinases (RTKs), a protein family that includes the notable member EGFR. Catechins, characterized by two chiral centers and stereoisomerism, demonstrate variations in chemical and physical properties due to differences in the spatial orientation of atoms. Although previous studies have explored the membrane fluidity effects and transport across cellular membranes, the stereo-selectivity of catechins concerning EGFR kinase inhibition remains unexplored. In this study, we investigated the stereo-selectivity of catechins in inhibiting EGFR kinase, both in its wild-type and in the prevalent L858R mutant. Computational analyses indicated that all stereoisomers, including the extensively studied catechin (-)-EGCG, effectively bound within the ATP-binding site, potentially inhibiting EGFR kinase activity. Notably, gallated catechins emerged as superior EGFR inhibitors to their non-gallated counterparts, revealing intriguing binding trends. The top four stereoisomers exhibiting high dock scores and binding energies with wild-type EGFR comprise (-)-CG (-)-GCG (+)-CG, and (-)-EGCG. To assess dynamic behavior and stability, molecular dynamics simulations over 100 ns were conducted for the top-ranked catechin (-)-CG and the widely investigated catechin (-)-EGCG with EGFR kinase. This study enhances our understanding of how the stereoisomeric nature of a drug influences inhibitory potential, providing insights that could guide the selection of specific stereoisomers for improved efficacy inexisting drugs.
ABSTRACT
The lack of precise molecular signatures limits the early diagnosis of non-small cell lung cancer (NSCLC). The present study used gene expression data and interaction networks to develop a highly accurate model with the least absolute shrinkage and selection operator (LASSO) for predicting NSCLC. The differentially expressed genes (DEGs) were identified in NSCLC compared with normal tissues using TCGA and GTEx data. A biological network was constructed using DEGs, and the top 20 upregulated and 20 downregulated hub genes were identified. These hub genes were used to identify signature genes with penalized logistic regression using the LASSO to predict NSCLC. Our model's development involved the following steps: (i) the dataset was divided into 80% for training (TR) and 20% for testing (TD1); (ii) a LASSO logistic regression analysis was performed on the TR with 10-fold cross-validation and identified a combination of 17 genes as NSCLC predictors, which were used further for development of the LASSO model. The model's performance was assessed on the TD1 dataset and achieved an accuracy and an area under the curve of the receiver operating characteristics (AUC-ROC) of 0.986 and 0.998, respectively. Furthermore, the performance of the LASSO model was evaluated using three independent NSCLC test datasets (GSE18842, GSE27262, GSE19804) and achieved high accuracy, with an AUC-ROC of >0.99, >0.99, and 0.95, respectively. Based on this study, a web application called NSCLCpred was developed to predict NSCLC.
ABSTRACT
In developing countries, acute respiratory infections (ARIs) cause a significant number of deaths among children. According to Bangladesh Demographic and Health Survey (BDHS), about 25% of the deaths in children under-five years are caused by ARI in Bangladesh every year. Low-income families frequently rely on wood, coal, and animal excrement for cooking. However, it is unclear whether using alternative fuels offers a health benefit over solid fuels. To clear this doubt, we conducted a study to investigate the effects of fuel usage on ARI in children. In this study, we used the latest BDHS 2017-18 survey data collected by the Government of Bangladesh (GoB) and estimated the effects of fuel use on ARI by constructing multivariable logistic regression models. From the analysis, we found that the crude (the only type of fuel in the model) odds ratio (OR) for ARI is 1.69 [95% confidence interval (CI): 1.06-2.71]. This suggests that children in families using contaminated fuels are 69.3% more likely to experience an ARI episode than children in households using clean fuels. After adjusting for cooking fuel, type of roof material, child's age (months), and sex of the child-the effect of solid fuels is similar to the adjusted odds ratio (AOR) for ARI (OR: 1.69, 95% CI: 1.05-2.72). This implies that an ARI occurrence is 69.2% more likely when compared to the effect of clean fuel. This study found a statistically significant association between solid fuel consumption and the occurrence of ARI in children in households. The correlation between indoor air pollution and clinical parameters of ARI requires further investigation. Our findings will also help other researchers and policymakers to take comprehensive actions by considering fuel type as a risk factor as well as taking proper steps to solve this issue.