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Immunological characterization of chitosan adjuvanted outer membrane proteins of Salmonella enterica serovar Typhi as multi-epitope typhoid vaccine candidate

Mol Biol Rep. 2022 Jun 17. doi: 10.1007/s11033-022-07531-w. Online ahead of print.

ABSTRACT

BACKGROUND: Outer membrane proteins (OMPs) of Gram-negative bacteria have been known as potential vaccine targets due to their antigenic properties and host specificity. Here, we focused on the exploration of the immunogenic potential and protective efficacy of total OMPs of Salmonella enterica serovar Typhi due to their multi epitope properties, adjuvanted with nanoporous chitosan particles (NPCPs). The study was designed to extrapolate an effective, low cost prophylactic approach for typhoid fever being getting uncontrolled in Pakistan due to emergence of extensively drug resistant (XDR) strains.

METHODS & RESULTS: The OMPs of two S. Typhi variants (with and without Vi capsule) alone and with nanoporous chitosan particles as adjuvant were comparatively analyzed for immunogenic potential in mice. Adaptive immunity was evaluated by ELISA and relative quantification of cytokine gene expression (IL4, IL6, IL9, IL17, IL10, TNF, INF and PPIA as house keeping gene) using RT-qPCR. Statistical analysis was done using Welch’s test. The protection was recorded by challenging the immunized mice with 50% ×LD50 of S. Typhi. The Vi + ve-OMPs of S. Typhi showed the most promising results by ELISA and significantly high expression of IL-6, IL-10 and IL-17 and 92.5% protective efficacy with no detectable side effects.

CONCLUSION: We can conclude that the OMPs of Vi + ve S. Typhi are the most promising candidates for future typhoid vaccines because of cost effective preparation without expensive purification steps and multi-epitope properties. Chitosan adjuvant may have applications for oral protein based vaccines but found less effective in injectable preparations.

PMID:35713798 | DOI:10.1007/s11033-022-07531-w

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Cohort Profile Update: the China Metal-Exposed workers Cohort Study (Jinchang Cohort)

Eur J Epidemiol. 2022 Jun 17. doi: 10.1007/s10654-022-00875-4. Online ahead of print.

ABSTRACT

The Jinchang Cohort was an ongoing 20-year ambispective cohort with unique metal exposures to an occupational population. From January 2014 to December 2019, the Jinchang Cohort has completed three phases of follow-up. The baseline cohort was completed from June 2011 to December 2013, and a total of 48 001 people were included. Three phases of follow-ups included 46 713, 41 888, and 40 530 participants, respectively. The death data were collected from 2001 to 2020. The epidemiological, physical examination, physiological, and biochemical data of the cohort were collected at baseline and during follow-up. Biological specimens were collected on the baseline to establish a biological specimen bank. The concentrations of metals in urine and serum were detected by inductively coupled plasma mass spectrometry (ICP-MS). The new areas of research aim to study the all-cases mortality, the burden of diseases, heavy metals and diseases, and the course of the chain from disease to high-risk outcomes using a combination of macro and micro means, which provided a scientific basis to explore the pathogenesis of multi-etiology and multi-disease and to evaluate the effects of the intervention measures in the population.

PMID:35713795 | DOI:10.1007/s10654-022-00875-4

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Incident Functional Limitations Among Community-Dwelling Adults Using Opioids: A Retrospective Cohort Study Using a Propensity Analysis with the Health and Retirement Study

Drugs Aging. 2022 Jun 17. doi: 10.1007/s40266-022-00953-y. Online ahead of print.

ABSTRACT

BACKGROUND: Opioid analgesics are commonly used to manage pain; however, it is unclear how they affect patient function. This study examines the association between opioid analgesics and incident limitations in activities of daily living (ADL), instrumental activities of daily living (IADL), and cognitive functioning among community-dwelling older adults.

METHODS: Data included 10,003 participants of the 2016 and 2018 waves of the Health and Retirement Study, which sampled US adults aged 51-98 years. The primary exposure was self-reported opioid pain medication use in 2016. Outcomes included incident limitations in ADL, IADL, and cognitive functioning in 2018. Statistical methods adjusted for confounding using multivariable logistic regressions, inverse probability of treatment weighting, and propensity scores.

RESULTS: Opioid use (adjusted odds ratio [aOR]: 1.34, 95% confidence interval [CI] 1.07-1.68) was associated with a statistically significant higher odds of incident ADL limitation in multivariable regression and in propensity score adjustment (aOR: 1.41, 95% CI 1.13-1.76). The association between opioid use and ADL and IADL limitations was modified by age. Adults aged < 65 years had a higher odds of incident ADL (aOR: 1.83, 95% CI 1.38-2.42) and IADL (aOR: 1.42, 95% CI 1.06-1.90) limitations compared with those aged ≥ 65 years.

CONCLUSIONS: Community-dwelling adults using opioid analgesics to manage pain may be at risk for incident ADL limitations. Middle-aged adults, compared with those older than 65 years of age, experienced the greatest odds for incident ADL and IADL limitations following opioid use. According to sensitivity analyses, our findings were robust to unmeasured confounding.

PMID:35713791 | DOI:10.1007/s40266-022-00953-y

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Antimicrobial effects of agitational irrigation on single- and multispecies biofilms in dentin canals

Odontology. 2022 Jun 17. doi: 10.1007/s10266-022-00719-3. Online ahead of print.

ABSTRACT

This study aimed to compare the antibacterial effects of different agitation devices on single- and multispecies biofilms in dentin canals using confocal laser scanning microscopy (CLSM). Dentin blocks were prepared from human root dentin. Enterococcus faecalis and multiple species were introduced into the dentinal tubules via centrifugation and incubation. Two infected dentin samples were placed at 8 and 16 mm in a customized model. Samples were randomly divided into eight groups according to the agitation device used: syringe needle irrigation, EndoActivator, passive ultrasonic irrigation (PUI), and EDDY, at 2.5% or 6% NaOCl concentrations. The samples were stained and observed using CLSM. Statistical analysis was performed using an independent sample t test and analysis of variance. Linear models were used to assess the joint impact of the experimental groups on the proportion of biofilms killed. No significant differences were observed between the killing rates of the single- and multispecies biofilms. Both concentrations of NaOCl significantly increased the percentage of dead bacteria compared with the control. Biofilms in dentin tubules was more effectively killed when NaOCl was agitated; however, the difference between PUI and EDDY was not significant. Significantly more bacteria were killed in dentin blocks placed at 8 mm than at 16 mm (p < 0.05). In conclusion, EDDY was as effective as PUI when combined with NaOCl. However, the apical portion, which had a low antimicrobial efficiency, remains a concern. Mechanical instrumentation is incapable of completely eradicating bacteria, and additional research is required to improve the efficacy of root canal disinfection.

PMID:35713740 | DOI:10.1007/s10266-022-00719-3

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QSAR, homology modeling, and docking simulation on SARS-CoV-2 and pseudomonas aeruginosa inhibitors, ADMET, and molecular dynamic simulations to find a possible oral lead candidate

J Genet Eng Biotechnol. 2022 Jun 17;20(1):88. doi: 10.1186/s43141-022-00362-z.

ABSTRACT

BACKGROUND: In seek of potent and non-toxic iminoguanidine derivatives formerly assessed as active Pseudomonas aeruginosa inhibitors, a combined mathematical approach of quantitative structure-activity relationship (QSAR), homology modeling, docking simulation, ADMET, and molecular dynamics simulations were executed on iminoguanidine derivatives.

RESULTS: The QSAR method was employed to statistically analyze the structure-activity relationships (SAR) and had conceded good statistical significance for eminent predictive model; (GA-MLR: Q2LOO = 0.8027; R2 = 0.8735; R2ext = 0.7536). Thorough scrutiny of the predictive models disclosed that the Centered Broto-Moreau autocorrelation – lag 1/weighted by I-state and 3D topological distance-based autocorrelation-lag 9/weighted by I-state oversee the biological activity and rendered much useful information to realize the properties required to develop new potent Pseudomonas aeruginosa inhibitors. The next mathematical model work accomplished here emphasizes finding a potential drug that could aid in curing Pseudomonas aeruginosa and SARS-CoV-2 as the drug targets Pseudomonas aeruginosa. This involves homology modeling of RNA polymerase-binding transcription factor DksA and COVID-19 main protease receptors, docking simulations, and pharmacokinetic screening studies of hits compounds against the receptor to identify potential inhibitors that can serve to regulate the modeled enzymes. The modeled protein exhibits the most favorable regions more than 90% with a minimum disallowed region less than 5% and is simulated under a hydrophilic environment. The docking simulations of all the series to the binding pocket of the built protein model were done to demonstrate their binding style and to recognize critical interacting residues inside the binding site. Their binding constancy for the modeled receptors has been assessed through RMSD, RMSF, and SASA analysis from 1-ns molecular dynamics simulations (MDS) run.

CONCLUSION: Our acknowledged drugs could be a proficient cure for SARS-CoV-2 and Pseudomonas aeruginosa drug discovery, having said that extra testing (in vitro and in vivo) is essential to explain their latent as novel drugs and manner of action.

PMID:35713736 | DOI:10.1186/s43141-022-00362-z

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AHP and TOPSIS based flood risk assessment- a case study of the Navsari City, Gujarat, India

Environ Monit Assess. 2022 Jun 17;194(7):509. doi: 10.1007/s10661-022-10111-x.

ABSTRACT

Flooding is one of the major natural catastrophic disasters that causes massive environmental and socioeconomic destruction. The magnitude of losses due to floods has prompted researchers to focus more on robust and comprehensive modeling approaches for alleviating flood damages. Recently developed multi-criteria decision making (MCDM) methods are being widely used to construct decision-making process more participatory, rational, and efficient. In this study, two statistical MCDM approaches, namely the analytical hierarchy process (AHP) and the technique for order preference by similarity to ideal solution (TOPSIS), have been employed to generate flood risk maps together with hazard and vulnerability maps in a GIS framework for Navsari city in Gujarat, India, to identify the vulnerable areas that are more susceptible to inundation during floods. The study area was divided into 10 sub areas (i.e., NC1 to NC10) to appraise the degree of flood hazard, vulnerability and risk intensities in terms of areal coverage and categorized under 5 intensity classes, viz., very low, low, moderate, high, and very high. A total of 14 flood indicators, seven each for hazard (i.e., elevation, slope, drainage density, distance to river, rainfall, soil, and flow accumulation) and vulnerability (i.e., population density, female population, land use, road network density, household, distance to hospital, and literacy rate) were considered for evaluating the flood risk. Flood risk coverage evaluated from the two approaches were compared with the flood extent computed from the actual flood data collected at 36 random locations. Results revealed that the TOPSIS approach estimated more precise flood risk coverage than the AHP approach, yielding high R2 values, i.e., 0.78 to 0.95 and low RMSE values, i.e., 0.95 to 0.43, for all the 5 risk intensity classes. The sub areas identified under “very high” and “high” risk intensity classes (i.e., NC1, NC4, NC6, NC7, NC8, and NC10) call for immediate flood control measures with a view to palliate the extent of flood risk and consequential damages. The study demonstrates the potential of AHP and TOPSIS integrated with GIS towards precise identification of flood-prone areas for devising effective flood management strategies.

PMID:35713716 | DOI:10.1007/s10661-022-10111-x

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Effect of light intensity on the tear production, central corneal thickness, and intraocular pressure in broiler chickens

Vet Ophthalmol. 2022 Jun 17. doi: 10.1111/vop.13005. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of the present study was to examine the effect of different light intensities on tear production, corneal thickness, and intraocular pressure in broilers.

ANIMALS STUDIED: Both eyes of 72 male broilers were evaluated in this study.

MATERIALS AND METHODS: Broilers were divided into the following three groups: low light intensity (n = 24, 5 lux), moderate light intensity (n = 24, 20 lux), and high light intensity (n = 24, 80 lux). The eyes of all birds (n = 72) underwent a complete ophthalmic examination, which included the Schirmer tear test (STT-I), intraocular pressure (IOP), and the central cornea thickness measurement (CCT). The effect of light intensity on the Schirmer test, intraocular pressure, and central corneal thickness values was examined at eye and animal level (right and left eyes separately and cumulatively/no distinguishing left or right) by using one-way ANOVA.

RESULTS: At the animal level, without discrimination of left and right eye measurements, statistically significant differences were found between 5-20 and 20-80 lux groups on IOP measurements (p < .05). The difference in CCT measurements between the 5 and 20 lux groups was statistically significant (p < .05), and the corneal thickness of the 5 lux group animals was found to be statistically significant and higher than the 20 lux group (p < .05).

CONCLUSIONS: In conclusion, light intensity has an influence on eye health in broilers. Present results may attribute to the future studies as a reference value for broilers raised under different light intensities.

PMID:35713163 | DOI:10.1111/vop.13005

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Investigating The Impacts of Working at Home Among Offıce Workers With Neck Pain on Health Status, Depression and Sleep Quality During COVID-19 Pandemic

Int J Occup Saf Ergon. 2022 Jun 17:1-25. doi: 10.1080/10803548.2022.2090132. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to assess the effect of workplace and ergonomic features on neck pain intensity, sleep problems, depression and health status at office workers during COVID-19 pandemic.

METHODS: One-hundred and thirty-nine office workers with neck pain who are 18-55 years of age were enrolled in the study. Sociodemographic features including ergonomic features of workplace were evaluated. The Beck Depression Inventory (BDI), the Nottingham Health Profile (NHP), the Pittsburgh Sleep Quality Index (PSQI), the Neck Pain and Disability Scale (NPDS) were administered to all patients.

RESULTS: All participants was grouped based on workplace into Group 1 (working in office n = 84) and Group 2(working at home n = 55). There was a statistically significant difference between the groups according to rate of absence of back support, flexible back (respectively p = 0.020 and p = 0.029). The scores of the Neck Pain and Disability Index scores of the participants who work with a computer more than 3 hours without break was higher in Group 2 than ın Group 1, and the differences between groups were found statistically significant (p = 0.001).

CONCLUSIONS: The health related quality of life was worse and neck pain intensity was severe in working at home group than working in office group.Trial registration:ClinicalTrials.gov identifier: NCT05074407..

PMID:35713149 | DOI:10.1080/10803548.2022.2090132

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CD163 in Macrophages: A Potential Biomarker for Predicting the Progression of Diabetic Nephropathy based on Bioinformatics Analysis

Endocr Metab Immune Disord Drug Targets. 2022 Jun 16. doi: 10.2174/1871530322666220616102754. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to identify the potential biomarkers in DN.

METHOD: DN dataset GSE30528 and GSE47183 were downloaded from Gene Expression Omnibus database. Immune cell infiltration was analyzed using CIBERSORT. Weighted gene co-expression network analysis (WGCNA) was performed to obtain the module genes specific to DN. The relevant genes were identified intersecting the module genes and differentially expression genes (DEGs). The core genes were identified using the MCC algorithm in Cytoscape software. ROC and Pearson analyses alongside gene set enrichment analysis (GSEA) were performed to identify the key gene for the core genes. Finally, we performed the Spearman to analyze the correlation between key gene and glomerular filtration rate (GFR), serum creatinine (Scr), age and sex in DN.

RESULTS: CIBERSORT analysis revealed the immune cell infiltration in the DN renal tissue and Venn identified 12 relevant genes. Among these, 5 core genes namely TYROBP, C1QA, C1QB, CD163 and MS4A6A, were identified. Pearson analyses revealed that immune cell infiltration and expression of core genes related. The key genes with high diagnostic values for DN were identified to be CD163 via ROC analyses. After Spearman correlation analysis, the expression level of CD163 was correlated with GFR (r =0.27), a difference that nearly reached statistical significance (P =0.058). However, there was no correlation between the level of CD163 and age (r =-0.24, P =0.09), sex (r =-0.11, P=0.32) and Scr (r=0.15, P=0.4) Conclusion: We found that CD163 in macrophages may be a potential biomarker in predicting and treating DN.

PMID:35713142 | DOI:10.2174/1871530322666220616102754

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Suicide exposure experience screener for use in therapeutic settings: A validation report

Suicide Life Threat Behav. 2022 Jun 17. doi: 10.1111/sltb.12894. Online ahead of print.

ABSTRACT

INTRODUCTION: A brief screener assessing experience of exposure to suicide for use in therapeutic settings is warranted. To examine the concurrent validity of such a screening tool, labeled as the Suicide Exposure Experience Screener (SEES), the associations of the two SEES items: (i) reported closeness with the person who died by suicide and (ii) perceived impact of suicide death with psychological distress are presented.

METHODS: Five separate datasets comprising surveys from Australia, Canada, and the United States (Ncombined = 7782) were used to provide evidence of concurrent validity of closeness and impact of suicide exposure.

RESULTS: Overall, closeness and impact were significantly correlated with measures of global distress across five different datasets, showing small to medium effect sizes. Closeness and impact were also intercorrelated demonstrating a large effect size across all surveys. This report used cross-sectional data and comprised varied sample sizes across different datasets that influenced statistical significance of obtained effects and did not tease apart the roles of cumulative exposure of suicide and prolonged bereavement in experiencing global distress.

CONCLUSION: The SEES has clinical utility in determining psychological distress in bereaved individuals and is recommended for use in therapeutic settings.

PMID:35713122 | DOI:10.1111/sltb.12894