Nevin Manimala

PLoS Negl Trop Dis. 2022 Sep 23;16(9):e0010722. doi: 10.1371/journal.pntd.0010722. Online ahead of print.

ABSTRACT

BACKGROUND: Shigella infections cause inflammation, which has been hypothesized to mediate the associations between Shigella and child development outcomes among children in low-resource settings. We aimed to assess whether early life inflammation and Shigella infections affect school-aged growth and cognitive outcomes from 6-8 years of age.

METHODOLOGY/PRINCIPAL FINDINGS: We conducted follow-up assessments of anthropometry, reasoning skills, and verbal fluency in 451 children at 6-8 years of age in the Brazil, Tanzania, and South Africa sites of MAL-ED, a longitudinal birth cohort study. We estimated the associations between Shigella burden and inflammation with linear growth at 2, 5, and 6-8 years of age, and with the cognitive test scores using linear regression and adjusting for potential confounding variables. We also assessed whether inflammation mediated the associations between Shigella and school-aged outcomes using a regression-based approach to mediation analysis. A high prevalence of Shigella was associated with a 0.32 (95% CI: 0.08, 0.56) z-score lower height-for-age z-score (HAZ) at 6-8 years compared to a low prevalence of Shigella. Intestinal inflammation had a smaller association with HAZ at 6-8 years. Shigella burden had small and consistently negative associations with cognitive outcomes in Brazil and Tanzania, but not South Africa, and the estimates were not statistically significant. Systemic inflammation was strongly associated with lower verbal fluency scores in Brazil (semantic fluency z-score difference: -0.57, 95% CI: -1.05, -0.10; phonemic fluency z-score difference: -0.48, 95% CI: -0.93, -0.03). There was no evidence that intestinal inflammation mediated the association between Shigella and HAZ or cognitive outcomes.

CONCLUSIONS/SIGNIFICANCE: While Shigella infections were consistently associated with long-term deficits in linear growth, the estimates of the negative associations between Shigella and cognitive outcomes were imprecise and only observed in the Brazil and Tanzania sites. Systemic inflammation was strongly associated with lower semantic and phonemic fluency scores in Brazil only, highlighting the site-specificity of effects.

PMID:36149931 | DOI:10.1371/journal.pntd.0010722

PLoS Pathog. 2022 Sep 23;18(9):e1010848. doi: 10.1371/journal.ppat.1010848. Online ahead of print.

ABSTRACT

Aneuploidy causes system-wide disruptions in the stochiometric balances of transcripts, proteins, and metabolites, often resulting in detrimental effects for the organism. The protozoan parasite Leishmania has an unusually high tolerance for aneuploidy, but the molecular and functional consequences for the pathogen remain poorly understood. Here, we addressed this question in vitro and present the first integrated analysis of the genome, transcriptome, proteome, and metabolome of highly aneuploid Leishmania donovani strains. Our analyses unambiguously establish that aneuploidy in Leishmania proportionally impacts the average transcript- and protein abundance levels of affected chromosomes, ultimately correlating with the degree of metabolic differences between closely related aneuploid strains. This proportionality was present in both proliferative and non-proliferative in vitro promastigotes. However, as in other Eukaryotes, we observed attenuation of dosage effects for protein complex subunits and in addition, non-cytoplasmic proteins. Differentially expressed transcripts and proteins between aneuploid Leishmania strains also originated from non-aneuploid chromosomes. At protein level, these were enriched for proteins involved in protein metabolism, such as chaperones and chaperonins, peptidases, and heat-shock proteins. In conclusion, our results further support the view that aneuploidy in Leishmania can be adaptive. Additionally, we believe that the high karyotype diversity in vitro and absence of classical transcriptional regulation make Leishmania an attractive model to study processes of protein homeostasis in the context of aneuploidy and beyond.

PMID:36149920 | DOI:10.1371/journal.ppat.1010848

PLoS One. 2022 Sep 23;17(9):e0275086. doi: 10.1371/journal.pone.0275086. eCollection 2022.

ABSTRACT

BACKGROUNDS: Micronutrient deficits in women of reproductive age have been linked to poor pregnancy outcomes. The most common micronutrient deficits in women are iron and folate. The World Health Organization recommends daily oral iron and folic acid supplementation (IFAS) as part of routine antenatal care to lower the risk of maternal anemia and adverse pregnancy outcomes. However, the effectiveness of the supplementation relies on client’s strict adherence. The aim of this study was to determine time- to- non-adherence to IFAS and associated factors among pregnant women in Hosanna Town, South Ethiopia.

METHODS: A community based cross sectional study design was employed from May 15-June11, 2021. Data were entered into Epi-Data version 3.1 and exported to SPSS version 23 for analysis. The Cox regression hazard model was applied. The threshold of statistical significance was declared at a p-value <0.05 and adjusted hazard ratios (AHRs) with corresponding 95% confidence intervals were used to report.

RESULT: The median time-to-non-adherence was 74 days (95 percent CI: 65.33-82.67). After adjusting for the confounders, age (AHR = 1.05, 95% CI: 1.01-1.09), education status (AHR = 2.43 95%CI 1.34-4.40, AHR 3.00, 95% CI: 2.09-4.31, AHR 1.91, 95% CI: 1.32-2.77), household’s wealth index (AHR = 1.73, 95% CI: 1.19-2.51, AHR = 1.64, 95% CI:1.15-2.35), and counseling at service delivery (AHR = 2.53, 95% CI: 1.88-3.41) were independent predictors of time to non-adherence to IFAS among pregnant women.

CONCLUSION: The median time to non-adherence was short and women became non-adherent before the recommended duration. Improving women’s education and counseling pregnant women on IFAS during pregnancy would make a change.

PMID:36149913 | DOI:10.1371/journal.pone.0275086

PLoS One. 2022 Sep 23;17(9):e0275032. doi: 10.1371/journal.pone.0275032. eCollection 2022.

ABSTRACT

BACKGROUND: Though initiation of insulin results in a significant change in glycemic levels, treating patients without significant hypoglycemic events remains difficult in diabetes patients initiated with different insulin-based regimens. This study assessed the association of hypoglycemic incidence and glycemic control between NPH and premixed insulin regimens in patients with type 2 diabetes mellitus (T2DM).

METHODS: This was a retrospective observational study in patients with T2DM who were treated with insulin-based therapy from 2015 to 2020 at the University of Gondar Comprehensive Specialized hospital. Average fasting blood glucose (FBG) between NPH and premixed insulin regimens was compared using an independent t-test. The Association of NPH and premixed insulin regimens with hypoglycemic incidences and glycemic control was examined by a logistic regression model. P < 0.05 was statistically significant.

RESULTS: From 405 participants, more than half (55.3%) were males with a mean age of 59.2(±9.1) years. Baseline mean HbA1C and FBG levels were 12.73(±1.1) % and 347.7(±48.5) mg/dl, respectively. Within a one-year follow-up period of insulin initiation, the rate of hypoglycemia was 13.1%. The incidence of hypoglycemia was significantly higher in patients initiated with premixed insulin compared with NPH insulin regimens (P < 0.001). After one year of insulin initiation, HbA1C decreased from 12.7 to 7.6 and from 12.8 to 7.3% and FBG levels decreased from 347.5 to 160.7 and from 348.2 to 147.3 mg/dl following initiation of NPH and premixed insulin, respectively. Patients treated with premixed-based insulin were found more likely to achieve target FBG compared with patients treated with NPH insulin regimens after one year of initiation (P = 0.02).

CONCLUSION: Premixed insulin-based regimen has found to have a higher hypoglycemic incidence, but a better level of glycemic control compared to NPH insulin-based therapy. Therefore, patients initiated with premixed insulin need to be highly vigilant and motivated to recognize the symptoms of hypoglycemia.

PMID:36149907 | DOI:10.1371/journal.pone.0275032

PLoS One. 2022 Sep 23;17(9):e0270545. doi: 10.1371/journal.pone.0270545. eCollection 2022.

ABSTRACT

INTRODUCTION: Voluntary medical male circumcision (VMMC) remains an effective biomedical intervention for HIV prevention in high HIV prevalence countries. In South Africa, United States Agency for International Development VMMC partners provide technical assistance to the Department of Health, at national and provincial levels in support of the establishment of VMMC sites as well as in providing direct VMMC services at site level since April 2012. We describe the outcomes of the Right to Care (RTC) VMMC program implemented in South Africa from 2012 to 2017.

METHODS: This retrospective study was undertaken at RTC supported facilities across six provinces. Young males aged ≥10 years who presented at these facilities from 1 July 2012 to 31 September 2017 were included. Outcomes were VMMC uptake, HIV testing uptake and rate of adverse events (AEs). Using a de-identified observational database of these clients, summary statistics of the demographic characteristics and outcomes were calculated.

RESULTS: There were a total 1,001,226 attendees of which 998,213 (99.7%) were offered VMMC and had a median age of 15 years (IQR = 12-23 years). Of those offered VMMC, 99.6% (994,293) consented, 96.7% (965,370) were circumcised and the majority (46.3%) were from Gauteng province. HIV testing uptake was 71% with a refusal rate of 15%. Of the newly diagnosed HIV positives, 64% (6,371 / 9,972) referrals were made. The rate of AEs, defined as bleeding, infection, and insufficient skin removal) declined from 3.26% in 2012 to 1.17% in 2017. There was a reduction in infection-related AEs from 2,448 of the 2,602 adverse events (94.08%) in 2012 to 129 of the 2,069 adverse events (6.23%) in 2017.

CONCLUSION: There was a high VMMC uptake with a decline in AEs over time. Adolescent men contributed the most to the circumcised population, an indication that the young population accesses medical circumcision more. VMMC programs need to implement innovative demand creation strategies to encourage older males (20-34 years) at higher risk of HIV acquisition to get circumcised for immediate impact in reduction of HIV incidence. HIV prevalence in the total population increased with increasing age, notably in clients above 25 years.

PMID:36149904 | DOI:10.1371/journal.pone.0270545

PLoS One. 2022 Sep 23;17(9):e0274026. doi: 10.1371/journal.pone.0274026. eCollection 2022.

ABSTRACT

Fibromyalgia-syndrome (FMS) is a complex disease characterized by chronic widespread pain and additional symptoms including depression, cognitive dysfunction (“fibro-fog”) and maldigestion. Our research team examined whether FMS-related pain parameters assessed by quantitative sensory testing (QST) and psychological disturbances are accompanied by alterations of the fecal microbiome. We recruited 25 patients with FMS and 26 age- and sex-matched healthy controls. Medical background, food habits, psychopathology and quality of life were assessed through questionnaires. Stool samples were analyzed by 16S rRNA gene amplification and sequencing. QST was performed according to the protocol of the German Network for Neuropathic Pain. QST showed that both lemniscal and spinothalamic afferent pathways are altered in FMS patients relative to healthy controls and that peripheral as well as central pain sensitization processes are manifest. Psychometric assessment revealed enhanced scores of depression, anxiety and stress. In contrast, neither the composition nor the alpha- and beta-diversity of the fecal microbiome was changed in FMS patients. FMS patients segregate from healthy controls in various parameters of QST and psychopathology, but not in terms of composition and diversity of the fecal microbiome. Despite consideration of several confounding factors, we conclude that the contribution of the gut microbiome to the pathophysiology of FMS is limited.

PMID:36149895 | DOI:10.1371/journal.pone.0274026

PLoS Biol. 2022 Sep 23;20(9):e3001804. doi: 10.1371/journal.pbio.3001804. Online ahead of print.

ABSTRACT

Following the initiation of the unprecedented global vaccination campaign against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), attention has now turned to the potential impact of this large-scale intervention on the evolution of the virus. In this Essay, we summarize what is currently known about pathogen evolution in the context of immune priming (including vaccination) from research on other pathogen species, with an eye towards the future evolution of SARS-CoV-2.

PMID:36149891 | DOI:10.1371/journal.pbio.3001804

ACS Nano. 2022 Sep 23. doi: 10.1021/acsnano.2c04089. Online ahead of print.

ABSTRACT

The diffusion and mobility in biomembranes are crucial for various cell functions; however, the mechanisms involved in such processes remain ambiguous due to the complex membrane structures. Herein, we investigate how the heterogeneous nanostructures cause anomalous diffusion in dipalmitoylphosphatidylcholine (DPPC) monolayers. By identifying the existence of condensed nanodomains and clarifying their impact, our findings renew the understanding of the hydrodynamic description and the statistical feature of the diffusion in the monolayers. We find a universal characteristic of the multistage mean square displacement (MSD) with an intermediate crossover, signifying two membrane viscosities at different scales: the short-time scale describes the local fluidity and is independent of the nominal DPPC density, and the long-time scale represents the global continuous phase taking into account nanodomains and increases with DPPC density. The constant short-time viscosity reflects a dynamic equilibrium between the continuous fluid phase and the condensed nanodomains in the molecular scale. Notably, we observe an “anomalous yet Brownian” phenomenon exhibiting an unusual double-peaked displacement probability distribution (DPD), which is attributed to the net dipolar repulsive force from the heterogeneous nanodomains around the microdomains. The findings provide physical insights into the transport of membrane inclusions that underpin various biological functions and drug deliveries.

PMID:36149751 | DOI:10.1021/acsnano.2c04089

JMIR Med Inform. 2022 Sep 23;10(9):e39746. doi: 10.2196/39746.

ABSTRACT

Electronic health records (EHRs) were originally developed for clinical care and billing. As such, the data are not collected, organized, and curated in a fashion that is optimized for secondary use to support the Learning Health System. Population health registries provide tools to support quality improvement. These tools are generally integrated with the live EHR, are intended to use a minimum of computing resources, and may not be appropriate for some research projects. Researchers may require different electronic phenotypes and variable definitions from those typically used for population health, and these definitions may vary from study to study. Establishing a formal registry that is mapped to the Observation Medical Outcomes Partnership common data model provides an opportunity to add custom mappings and more easily share these with other institutions. Performing preprocessing tasks such as data cleaning, calculation of risk scores, time-to-event analysis, imputation, and transforming data into a format for statistical analyses will improve efficiency and make the data easier to use for investigators. Research registries that are maintained outside the EHR also have the luxury of using significant computational resources without jeopardizing clinical care data. This paper describes a virtual Diabetes Registry at Atrium Health Wake Forest Baptist and the plan for its continued development.

PMID:36149742 | DOI:10.2196/39746

JMIR Res Protoc. 2022 Sep 23;11(9):e38608. doi: 10.2196/38608.

ABSTRACT

BACKGROUND: Sleep disturbances post concussion have been associated with more frequent and severe concussion symptoms and may contribute to poorer recovery. Cognitive behavioral therapy for insomnia (CBT-I) is an effective treatment for insomnia; however, it remains unclear if this treatment method is effective in improving sleep outcomes and reducing concomitant postconcussion symptoms.

OBJECTIVE: The hypotheses for this study are that (1) CBT-I will improve sleep outcomes and (2) CBT-I will improve concomitant postconcussion symptoms.

METHODS: In total, 40 individuals who are within ≥4 weeks of postconcussion injury and have insomnia symptoms will be enrolled in this randomized controlled trial. Participants will be randomized into either a group that starts a 6-week CBT-I program immediately after baseline or a waitlist control group that starts CBT-I following a 6-week waiting period. All participants will be reassessed 6, 12, and 18 weeks after baseline. Standardized assessments measuring sleep outcomes, postconcussion symptoms, and mood will be used. Linear regression and t tests will be used for statistical analyses.

RESULTS: Enrollment of 40 participants was completed July 2022, data collection will be completed in November 2022, and publication of main findings is anticipated in May 2023. It is anticipated that participants experience reduced insomnia symptoms and postconcussion symptoms following CBT-I and these improvements will be retained for at least 12 weeks. Additionally, we expect to observe a positive correlation between sleep and postconcussion symptom improvement.

CONCLUSIONS: Successful completion of this pilot study will allow for a better understanding of the treatment of insomnia and postconcussion symptoms in individuals following a concussion.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04885205; https://clinicaltrials.gov/ct2/show/NCT04885205.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38608.

PMID:36149737 | DOI:10.2196/38608