Tag: nevin manimala

PLoS One. 2023 Mar 30;18(3):e0283537. doi: 10.1371/journal.pone.0283537. eCollection 2023.

ABSTRACT

Zoonotic spillover of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to humans in December 2019 caused the coronavirus disease 2019 (COVID-19) pandemic. Serological monitoring is critical for detailed understanding of individual immune responses to infection and protection to guide clinical therapeutic and vaccine strategies. We developed a high throughput multiplexed SARS-CoV-2 antigen microarray incorporating spike (S) and nucleocapsid protein (NP) and fragments expressed in various hosts which allowed simultaneous assessment of serum IgG, IgA, and IgM responses. Antigen glycosylation influenced antibody binding, with S glycosylation generally increasing and NP glycosylation decreasing binding. Purified antibody isotypes demonstrated a binding pattern and intensity different from the same isotype in whole serum, probably due to competition from the other isotypes present. Using purified antibody isotypes from naïve Irish COVID-19 patients, we correlated antibody isotype binding to different panels of antigens with disease severity, with binding to the S region S1 expressed in insect cells (S1 Sf21) significant for IgG, IgA, and IgM. Assessing longitudinal response for constant concentrations of purified antibody isotypes for a patient subset demonstrated that the relative proportion of antigen-specific IgGs decreased over time for severe disease, but the relative proportion of antigen-specific IgA binding remained at the same magnitude at 5 and 9 months post-first symptom onset. Further, the relative proportion of IgM binding decreased for S antigens but remained the same for NP antigens. This may support antigen-specific serum IgA and IgM playing a role in maintaining longer-term protection, important for developing and assessing vaccine strategies. Overall, these data demonstrate the multiplexed platform as a sensitive and useful platform for expanded humoral immunity studies, allowing detailed elucidation of antibody isotypes response against multiple antigens. This approach will be useful for monoclonal antibody therapeutic studies and screening of donor polyclonal antibodies for patient infusions.

PMID:36996259 | DOI:10.1371/journal.pone.0283537

PLoS One. 2023 Mar 30;18(3):e0283629. doi: 10.1371/journal.pone.0283629. eCollection 2023.

ABSTRACT

BACKGROUND: Vaccination is a global success story, one of the most effective and successful health interventions for health and development, saving the lives of millions of children every year. In 2018, nearly 870,000 Ethiopian children did not receive the life-saving measles, diphtheria, and tetanus vaccines. This study aimed to determine what factors influence children’s immunization status in Ethiopia.

METHODS: Immunization status was examined in a sample of 1843 children aged 12-24 months using data from the 2019 Ethiopian Mini Demographic and Health Survey 2019. The study used percentages to show the prevalence of immunization status among children. The marginal likelihood effect was used to determine the impact of each category of the explanatory variable on one response category of immunization status. Ordinal logistic regression models were constructed, and the best-fitting model was selected to identify significant immunization status variables.

RESULTS: The immunization prevalence among children was 72.2% (34.2% fully immunized and 38.0% partially immunized), while about 27.8% of children were non-immunized. The fitted partial proportional odds model revealed that child immunization status was significantly associated with region afar (OR = 7.90; CI: 4.78-11.92), family planning use (OR = 0.69; CI: 0.54-0.88), residence (OR = 2.22;CI: 1.60-3.09), antenatal visit (OR = 0.73;CI: 0.53-0.99), and delivery place (OR = 0.65;CI: 0.50-0.84).

CONCLUSIONS: Vaccinating children was a significant step forward in improving and protecting child health in Ethiopia, as the proportion of non-immunized children was about 27.8%. The study showed that the prevalence of non-immunization status among rural children was 33.6% and about 36.6% among children from non-educated mothers. As a result, it is agreeable that treatments are better to focus on targeting essential childhood vaccinations by promoting maternal education about family planning, antenatal visits, and maternal access to health care.

PMID:36996256 | DOI:10.1371/journal.pone.0283629

PLoS One. 2023 Mar 30;18(3):e0280315. doi: 10.1371/journal.pone.0280315. eCollection 2023.

ABSTRACT

INTRODUCTION: Despite much emphasis on the reproductive health of women, maternal mortality is still high, especially in postnatal period.

OBJECTIVE: To assess the prevalence of postnatal care use and reasons for defaults among mothers attending the child immunization clinics in Enugu, Nigeria.

METHODS: This was a cross-sectional comparative study of 400 consecutive nursing mothers who presented at the Institute of Child Health of UNTH and ESUTH, Enugu for Second dose of the Oral Polio Vaccine (OPV2) for their babies at 10 weeks postpartum. Data was collected using Interviewer-administered questionnaire and subsequently analyzed with version 22.0 IBM SPSS software, Chicago, Illinois. A p-value of less than 0.05 was considered as statistically significant.

RESULT: The prevalence of the 6th week postnatal clinic attendance among the mothers was 59%. The majority of the women (60.6%) who had antenatal care by skilled birth attendants attended postnatal clinic. Unawareness and being healthy were the main reasons for not attending postnatal clinic. Following multivariate analysis, place of antenatal (OR = 2.870, 95% C.I = 1.590-5.180, p < 0.001) and mode of delivery (OR = 0.452, 95% C.I = 0.280-0.728, p = 0.001) were the only significant predictors of postnatal clinic attendance (p < 0.05).

CONCLUSION: Postnatal clinic attendance by women in Enugu is still suboptimal. The main reason for non-attendance of the 6th week postnatal clinic was lack of awareness. There is need for healthcare professionals to create awareness about the importance of postnatal care and encourage mothers to attend.

PMID:36996250 | DOI:10.1371/journal.pone.0280315

PLoS One. 2023 Mar 30;18(3):e0283313. doi: 10.1371/journal.pone.0283313. eCollection 2023.

ABSTRACT

Statistical physics is widely used to study the nonlinear mechanical behaviors of rock. For the limitations of existing statistical damage models and Weibull distribution, a new statistical damage with lateral damage is established. In addition, by introducing the maximum entropy distribution function and the strict constraint on damage variable, a expression of the damage variable matching the proposed model is obtained. Through comparing with the experimental results and the other two statistical damage models, the rationality of the maximum entropy statistical damage model is confirmed. The proposed model can better reflect the strain-softening behavior for rocks and respond to the residual strength, which provides a theoretical reference for practical engineering construction and design.

PMID:36996233 | DOI:10.1371/journal.pone.0283313

Alzheimers Res Ther. 2023 Mar 29;15(1):67. doi: 10.1186/s13195-022-01135-z.

ABSTRACT

BACKGROUND: Individuals from minority ethnic groups in the UK are thought to be at higher risk of developing dementia while facing additional barriers to receiving timely care. However, few studies in the UK have examined if there are ethnic disparities in survival once individuals receive a dementia diagnosis.

METHODS: We conducted a retrospective cohort study using electronic health record data of individuals diagnosed with dementia from a large secondary mental healthcare provider in London. Patients from Black African, Black Caribbean, South Asian, White British, and White Irish ethnic backgrounds were followed up for a 10-year period between 01 January 2008 and 31 December 2017. Data were linked to death certificate data from the Office of National Statistics to determine survival from dementia diagnosis. Standardised mortality ratios were calculated to estimate excess deaths in each ethnicity group as compared to the gender- and age-standardised population of England and Wales. We used Cox regression models to compare survival after dementia diagnosis across each ethnicity group.

RESULTS: Mortality was elevated at least twofold across all ethnicity groups with dementia compared to the general population in England and Wales. Risk of death was lower in Black Caribbean, Black African, White Irish, and South Asian groups as compared to the White British population, even after adjusting for age, gender, neighbourhood-level deprivation, indicators of mental and physical comorbidities. Risk of death remained lower after additionally accounting for those who emigrated out of the cohort.

CONCLUSIONS: While mortality in dementia is elevated across all ethnic groups as compared to the general population, reasons for longer survival in minority ethnic groups in the UK as compared to the White British group are unclear and merit further exploration. Implications of longer survival, including carer burden and costs, should be considered in policy and planning to ensure adequate support for families and carers of individuals with dementia.

PMID:36991518 | DOI:10.1186/s13195-022-01135-z

Hum Genomics. 2023 Mar 30;17(1):31. doi: 10.1186/s40246-023-00478-4.

ABSTRACT

BACKGROUND: Genome-wide association studies (GWAS) have highlighted over 200 autosomal variants associated with multiple sclerosis (MS). However, variants in non-coding regions such as those encoding microRNAs have not been explored thoroughly, despite strong evidence of microRNA dysregulation in MS patients and model organisms. This study explores the effect of microRNA-associated variants in MS, through the largest publicly available GWAS, which involved 47,429 MS cases and 68,374 controls.

METHODS: We identified SNPs within the coordinates of microRNAs, ± 5-kb microRNA flanking regions and predicted 3’UTR target-binding sites using miRBase v22, TargetScan 7.0 RNA22 v2.0 and dbSNP v151. We established the subset of microRNA-associated SNPs which were tested in the summary statistics of the largest MS GWAS by intersecting these datasets. Next, we prioritised those microRNA-associated SNPs which are among known MS susceptibility SNPs, are in strong linkage disequilibrium with the former or meet a microRNA-specific Bonferroni-corrected threshold. Finally, we predicted the effects of those prioritised SNPs on their microRNAs and 3’UTR target-binding sites using TargetScan v7.0, miRVaS and ADmiRE.

RESULTS: We have identified 30 candidate microRNA-associated variants which meet at least one of our prioritisation criteria. Among these, we highlighted one microRNA variant rs1414273 (MIR548AC) and four 3’UTR microRNA-binding site variants within SLC2A4RG (rs6742), CD27 (rs1059501), MMEL1 (rs881640) and BCL2L13 (rs2587100). We determined changes to the predicted microRNA stability and binding site recognition of these microRNA and target sites.

CONCLUSIONS: We have systematically examined the functional, structural and regulatory effects of candidate MS variants among microRNAs and 3’UTR targets. This analysis allowed us to identify candidate microRNA-associated MS SNPs and highlights the value of prioritising non-coding RNA variation in GWAS. These candidate SNPs could influence microRNA regulation in MS patients. Our study is the first thorough investigation of both microRNA and 3’UTR target-binding site variation in multiple sclerosis using GWAS summary statistics.

PMID:36991503 | DOI:10.1186/s40246-023-00478-4

J Cannabis Res. 2023 Mar 30;5(1):11. doi: 10.1186/s42238-023-00179-8.

ABSTRACT

INTRODUCTION: Cannabidiol (CBD) is a potential therapeutic for pain management. Yet, there exists a dearth of studies of its tolerability and efficacy, especially in special populations. Former elite athletes are a special population both susceptible to chronic pain and also highly trained and attuned to assess medication tolerability concerns. The purpose of the present open-label pilot study was to assess the tolerability of CBD in this population.

MATERIALS AND METHODS: Retrospective analysis was conducted in deidentified data from 20 individuals who were all previously professional athletes in US/American football, track and field, or basketball, with careers ranging from 4 to 10 years. Participants received topical CBD (10 mg twice daily by controlled dispenser) for chronic pain resulting from acute lower extremity injuries. Assessments of tolerability and secondary analyses of pain, pain-related disability, and activities of daily living were collected by self-report over the 6-week study period. Data were analyzed by descriptive statistics, pairwise t-test, and linear regression.

RESULTS: Seventy percent of participants completed the study. Of the individuals who completed the study, 50% reported minor adverse effects, none of which required medical attention, and 50% did not report any adverse effects. The mostly commonly reported effects were skin dryness (43% of study completers) and skin rash (21% of study completers), which rapidly resolved. There was a significant improvement in self-reported pain levels (intake mean 3.5 ± 0.29; exit mean 1.7 ± 0.23; P < 0.001) and pain-related disability, including family and home responsibilities, life support activities, occupational activities, recreational activities, self-care, sexual function, and social activities (all P < 0.001).

DISCUSSION: To the best of our knowledge, this is the first study to assess CBD treatment in elite athletes, who are disproportionally susceptible to disabling injuries. Topical administration of CBD was tolerated well by this population and resulted in only minor adverse effects. As elite athletes are trained and attuned to assess their own bodies due to their professional lives, this population is likely to detect tolerability concerns. However, this study was limited to a convenience sample and self-reported data. These pilot findings warrant further study of topical CBD in randomized and controlled studies of elite athletes.

PMID:36991501 | DOI:10.1186/s42238-023-00179-8

BMC Med Genomics. 2023 Mar 29;16(1):64. doi: 10.1186/s12920-023-01488-w.

ABSTRACT

BACKGROUND: Detection of appropriate receptor proteins and drug agents are equally important in the case of drug discovery and development for any disease. In this study, an attempt was made to explore colorectal cancer (CRC) causing molecular signatures as receptors and drug agents as inhibitors by using integrated statistics and bioinformatics approaches.

METHODS: To identify the important genes that are involved in the initiation and progression of CRC, four microarray datasets (GSE9348, GSE110224, GSE23878, and GSE35279) and an RNA_Seq profiles (GSE50760) were downloaded from the Gene Expression Omnibus database. The datasets were analyzed by a statistical r-package of LIMMA to identify common differentially expressed genes (cDEGs). The key genes (KGs) of cDEGs were detected by using the five topological measures in the protein-protein interaction network analysis. Then we performed in-silico validation for CRC-causing KGs by using different web-tools and independent databases. We also disclosed the transcriptional and post-transcriptional regulatory factors of KGs by interaction network analysis of KGs with transcription factors (TFs) and micro-RNAs. Finally, we suggested our proposed KGs-guided computationally more effective candidate drug molecules compared to other published drugs by cross-validation with the state-of-the-art alternatives of top-ranked independent receptor proteins.

RESULTS: We identified 50 common differentially expressed genes (cDEGs) from five gene expression profile datasets, where 31 cDEGs were downregulated, and the rest 19 were up-regulated. Then we identified 11 cDEGs (CXCL8, CEMIP, MMP7, CA4, ADH1C, GUCA2A, GUCA2B, ZG16, CLCA4, MS4A12 and CLDN1) as the KGs. Different pertinent bioinformatic analyses (box plot, survival probability curves, DNA methylation, correlation with immune infiltration levels, diseases-KGs interaction, GO and KEGG pathways) based on independent databases directly or indirectly showed that these KGs are significantly associated with CRC progression. We also detected four TFs proteins (FOXC1, YY1, GATA2 and NFKB) and eight microRNAs (hsa-mir-16-5p, hsa-mir-195-5p, hsa-mir-203a-3p, hsa-mir-34a-5p, hsa-mir-107, hsa-mir-27a-3p, hsa-mir-429, and hsa-mir-335-5p) as the key transcriptional and post-transcriptional regulators of KGs. Finally, our proposed 15 molecular signatures including 11 KGs and 4 key TFs-proteins guided 9 small molecules (Cyclosporin A, Manzamine A, Cardidigin, Staurosporine, Benzo[A]Pyrene, Sitosterol, Nocardiopsis Sp, Troglitazone, and Riccardin D) were recommended as the top-ranked candidate therapeutic agents for the treatment against CRC.

CONCLUSION: The findings of this study recommended that our proposed target proteins and agents might be considered as the potential diagnostic, prognostic and therapeutic signatures for CRC.

PMID:36991484 | DOI:10.1186/s12920-023-01488-w

Arthritis Res Ther. 2023 Mar 29;25(1):51. doi: 10.1186/s13075-023-03033-7.

ABSTRACT

OBJECTIVE: To estimate the global prevalence of hip osteoarthritis (HOA) through a systematic review and meta-analysis, and to determine by regression analysis the respective relationships between age and sex, and sex and prevalence.

METHODS: EMBASE, PubMed, Web of science, CINAHL, and SCOPUS were searched from inception until August 2022. Two authors independently extracted data and assessed the quality of the retrieved literature. Random-effects meta-analysis was performed to derive the pooled prevalence. Variations in the prevalence estimate in different subgroups, including diagnostic methods, region, and patient sex, were examined by subgroup meta-analysis. Meta-regression was used to construct the age-specific prevalence of HOA.

RESULTS: A total of 31 studies were included in our analysis, involving 326,463 participants. Quality evaluation showed that all studies included in the analysis had a Quality Score of at least 4. The most frequently used method for diagnosing HOA was the Kellgren-Lawrence (K-L) grade classification, accounting for 19/31 (61.3%) studies. The pooled prevalence of HOA diagnosed based on the K-L grade ≥ 2 criterion was 8.55% (95% CI 4.85-13.18) worldwide. The prevalence of HOA was lowest in Africa at 1.20% (95% CI: 0.40-2.38), followed by Asia at 4.26% (95% CI 0.02-14.93) and North America at 7.95% (95% CI 1.98-17.36), and highest in Europe at 12.59% (95% CI 7.17-19.25). There was no statistically significant difference in HOA prevalence between men (9.42%, 95% CI:4.81-15.34) and women at (7.94%, 95% CI: 3.57-13.81). The regression model showed a correlation between age and the prevalence of HOA.

CONCLUSION: HOA has high prevalence worldwide and increases with age. The prevalence varies significantly by region but not by patient sex. High-quality epidemiological studies are warranted to more accurately estimate the prevalence of HOA.

PMID:36991481 | DOI:10.1186/s13075-023-03033-7

BMC Endocr Disord. 2023 Mar 29;23(1):69. doi: 10.1186/s12902-023-01325-2.

ABSTRACT

BACKGROUND: A high resting heart rate (HR) has been associated with an increased risk of diabetes mellitus. This study explored the association between initial in-hospital HR and glycemic control in patients with acute ischemic stroke (AIS) and diabetes mellitus.

METHODS: We analyzed data from 4,715 patients with AIS and type 2 diabetes mellitus enrolled in the Chang Gung Research Database between January 2010 and September 2018. The study outcome was unfavorable glycemic control, defined as glycated hemoglobin (HbA1c) ≥ 7%. In statistical analyses, the mean initial in-hospital HR was used as both a continuous and categorical variable. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression analysis. The associations between the HR subgroups and HbA1c levels were analyzed using a generalized linear model.

RESULTS: Compared with the reference group (HR < 60 bpm), the adjusted ORs for unfavorable glycemic control were 1.093 (95% CI 0.786-1.519) for an HR of 60-69 bpm, 1.370 (95% CI 0.991-1.892) for an HR of 70-79 bpm, and 1.608 (95% CI 1.145-2.257) for an HR of ≥ 80 bpm. Even after adjusting for possible confounders, the HbA1c levels after admission and discharge among diabetic stroke patients increased significantly in the subgroups with higher HRs (p < 0.001).

CONCLUSIONS: High initial in-hospital HR is associated with unfavorable glycemic control in patients with AIS and diabetes mellitus, particularly in those with an HR of ≥ 80 bpm, compared with those with an HR of < 60 bpm.

PMID:36991469 | DOI:10.1186/s12902-023-01325-2