Category: Nevin Manimala

Proc Natl Acad Sci U S A. 2023 Jun 6;120(23):e2302107120. doi: 10.1073/pnas.2302107120. Epub 2023 May 30.

ABSTRACT

Helping strangers at a cost to oneself is a hallmark of many human interactions, but difficult to justify from the viewpoint of natural selection, particularly in anonymous one-shot interactions. Reputational scoring can provide the necessary motivation via “indirect reciprocity,” but maintaining reliable scores requires close oversight to prevent cheating. We show that in the absence of such supervision, it is possible that scores might be managed by mutual consent between the agents themselves instead of by third parties. The space of possible strategies for such “consented” score changes is very large but, using a simple cooperation game, we search it, asking what kinds of agreement can i) invade a population from rare and ii) resist invasion once common. We prove mathematically and demonstrate computationally that score mediation by mutual consent does enable cooperation without oversight. Moreover, the most invasive and stable strategies belong to one family and ground the concept of value by incrementing one score at the cost of the other, thus closely resembling the token exchange that underlies money in everyday human transactions. The most successful strategy has the flavor of money except that agents without money can generate new score if they meet. This strategy is evolutionarily stable, and has higher fitness, but is not physically realizable in a decentralized way; when conservation of score is enforced more money-like strategies dominate. The equilibrium distribution of scores under any of this family of strategies is geometric, meaning that agents with score 0 are inherent to money-like strategies.

PMID:37253000 | DOI:10.1073/pnas.2302107120

Proc Natl Acad Sci U S A. 2023 Jun 6;120(23):e2216932120. doi: 10.1073/pnas.2216932120. Epub 2023 May 30.

ABSTRACT

Dietary flavanols are food constituents found in certain fruits and vegetables that have been linked to cognitive aging. Previous studies suggested that consumption of dietary flavanols might specifically be associated with the hippocampal-dependent memory component of cognitive aging and that memory benefits of a flavanol intervention might depend on habitual diet quality. Here, we tested these hypotheses in the context of a large-scale study of 3,562 older adults, who were randomly assigned to a 3-y intervention of cocoa extract (500 mg of cocoa flavanols per day) or a placebo [(COcoa Supplement and Multivitamin Outcomes Study) COSMOS-Web, NCT04582617]. Using the alternative Healthy Eating Index in all participants and a urine-based biomarker of flavanol intake in a subset of participants [n = 1,361], we show that habitual flavanol consumption and diet quality at baseline are positively and selectively correlated with hippocampal-dependent memory. While the prespecified primary end point testing for an intervention-related improvement in memory in all participants after 1 y was not statistically significant, the flavanol intervention restored memory among participants in lower tertiles of habitual diet quality or habitual flavanol consumption. Increases in the flavanol biomarker over the course of the trial were associated with improving memory. Collectively, our results allow dietary flavanols to be considered in the context of a depletion-repletion paradigm and suggest that low flavanol consumption can act as a driver of the hippocampal-dependent component of cognitive aging.

PMID:37252983 | DOI:10.1073/pnas.2216932120

Proc Natl Acad Sci U S A. 2023 Jun 6;120(23):e2218200120. doi: 10.1073/pnas.2218200120. Epub 2023 May 30.

ABSTRACT

The distribution of fitness effects (DFE) of new mutations is key to our understanding of many evolutionary processes. Theoreticians have developed several models to help understand the patterns seen in empirical DFEs. Many such models reproduce the broad patterns seen in empirical DFEs but these models often rely on structural assumptions that cannot be tested empirically. Here, we investigate how much of the underlying “microscopic” biological processes involved in the mapping of new mutations to fitness can be inferred from “macroscopic” observations of the DFE. We develop a null model by generating random genotype-to-fitness maps and show that the null DFE is that with the largest possible information entropy. We further show that, subject to one simple constraint, this null DFE is a Gompertz distribution. Finally, we illustrate how the predictions of this null DFE match empirically measured DFEs from several datasets, as well as DFEs simulated from Fisher’s geometric model. This suggests that a match between models and empirical data is often not a very strong indication of the mechanisms underlying the mapping of mutation to fitness.

PMID:37252948 | DOI:10.1073/pnas.2218200120

PLoS Biol. 2023 May 30;21(5):e3001665. doi: 10.1371/journal.pbio.3001665. eCollection 2023 May.

ABSTRACT

Epithelial repair relies on the activation of stress signaling pathways to coordinate tissue repair. Their deregulation is implicated in chronic wound and cancer pathologies. Using TNF-α/Eiger-mediated inflammatory damage to Drosophila imaginal discs, we investigate how spatial patterns of signaling pathways and repair behaviors arise. We find that Eiger expression, which drives JNK/AP-1 signaling, transiently arrests proliferation of cells in the wound center and is associated with activation of a senescence program. This includes production of the mitogenic ligands of the Upd family, which allows JNK/AP-1-signaling cells to act as paracrine organizers of regeneration. Surprisingly, JNK/AP-1 cell-autonomously suppress activation of Upd signaling via Ptp61F and Socs36E, both negative regulators of JAK/STAT signaling. As mitogenic JAK/STAT signaling is suppressed in JNK/AP-1-signaling cells at the center of tissue damage, compensatory proliferation occurs by paracrine activation of JAK/STAT in the wound periphery. Mathematical modelling suggests that cell-autonomous mutual repression between JNK/AP-1 and JAK/STAT is at the core of a regulatory network essential to spatially separate JNK/AP-1 and JAK/STAT signaling into bistable spatial domains associated with distinct cellular tasks. Such spatial stratification is essential for proper tissue repair, as coactivation of JNK/AP-1 and JAK/STAT in the same cells creates conflicting signals for cell cycle progression, leading to excess apoptosis of senescently stalled JNK/AP-1-signaling cells that organize the spatial field. Finally, we demonstrate that bistable separation of JNK/AP-1 and JAK/STAT drives bistable separation of senescent signaling and proliferative behaviors not only upon tissue damage, but also in RasV12, scrib tumors. Revealing this previously uncharacterized regulatory network between JNK/AP-1, JAK/STAT, and associated cell behaviors has important implications for our conceptual understanding of tissue repair, chronic wound pathologies, and tumor microenvironments.

PMID:37252939 | DOI:10.1371/journal.pbio.3001665

PLoS One. 2023 May 30;18(5):e0286262. doi: 10.1371/journal.pone.0286262. eCollection 2023.

ABSTRACT

BACKGROUNDS: Worldwide, a substantial proportion of women have low cervical cancer screening services utilization. There is a paucity of evidence in utilization of cervical cancer screening services among female health workers and inconsistent findings in Ethiopia. This study aimed to assess the utilization of cervical cancer screening services and associated factors among female health workers in public health facilities of Hossana town, Southern Ethiopia.

METHODS: Facility-based cross-sectional study design complemented with the qualitative inquiry was conducted among randomly selected 241 study participants in Hossana town from June 1 to July 1, 2021. Logistic regression models were used to determine the association between dependent and independent variables with the assumption of a variable with a p-value < 0.05 was considered statistically significant. Qualitative data were transcribed verbatim then translated to English and analyzed using open code version 4.03.

RESULTS: Out of the total study participants, 19.6% was screened for cervical cancer. Having a diploma level of education (AOR = 0.48;95%CI:0.24,0.98), having three or more children (AOR = 3.65;95%CI:1.44,9.21), having multiple sexual partners(AOR = 3.89;95%CI: 1.38,11.01), and knowledge of cervical cancer screening (AOR = 2.66;95% CI:1.19,5.95) were statistically significantly associated with cervical cancer screening utilization. In-depth interviews suggested additional barriers for low screening utilization including lack of health educational materials, limitation of service to a specific area, service interruption, provider incompetency, and miss-trust and lack of attention by a trained provider.

CONCLUSION: Utilization of cervical cancer screening service among female health workers is low. Having a diploma level of education, having three or more children, a history of multiple sexual partners, and knowledge about cervical cancer were predictors of cervical cancer screening utilization. Contextualized health talks and promotion through training with a special focus on low level of knowledge, had lower educational level, and the availability of cervical cancer screening services are critical.

PMID:37252937 | DOI:10.1371/journal.pone.0286262

PLoS One. 2023 May 30;18(5):e0286398. doi: 10.1371/journal.pone.0286398. eCollection 2023.

ABSTRACT

BACKGROUND: People experienced various stress and psychological responses to the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to examine the changes in emergency medical services (EMSs) utilization by self-harm patients in early pandemic and the impacts of physical distancing measures on the EMSs utilization by self-harm patients.

METHODS: Data for all patients presenting to emergency departments (EDs) after self-harm injuries including self-poisoning were collected from the National ED Information System (NEDIS). Characteristics of patients in two study regions (urban versus rural) were compared. Weekly and annual ED visit rates after self-harm (VRSH) per 100,000 population were calculated. Mobile phone mobility index (MPMI) was calculated by dividing a region’s aggregated mobile phone mobility by mid-year population. Joinpoint regression analysis was conducted to assess changes in 2020 over pre-pandemic years. Test for presence of joinpoint at the end of 2019 was performed. A cross-correlation function was used to estimate the maximal morphological similarity and lag time between changes in MPMI and VRSH.

RESULTS: In 2020, in early phases of the pandemic, there was a moderate decline in self-harm-related ED visits to 30,797 from a continuously increasing trend seen in previous years. However, proportions of young people (50.1%) and females (62.3%) increased over previous years. VRSHs among women and young people aged 15-34 years showed higher levels in 2020 than in previous five years. There was a significant decrease in the proportion of patients transported directly from the scene. In addition, there was a polarization of mental state upon ED arrival from alert and unresponsive. The median correlation coefficient between MPMI values and VRSH values was 0.601 (interquartile range [IQR]: 0.539-0.619) in urban regions and 0.531 (IQR: 0.454-0.595) in rural regions, showing no statistically significant difference between the two.

CONCLUSION: Physical distancing measures adopted to prevent the spread of transmittable diseases following the pandemic had the effect of decreasing ED visits due to self-harm. When the pandemic has ended, and daily life has been restored, it will be particularly important to pay attention to the increased numbers of self-harm patients expected to visit EDs compared to during the pandemic.

PMID:37252929 | DOI:10.1371/journal.pone.0286398

PLoS One. 2023 May 30;18(5):e0286259. doi: 10.1371/journal.pone.0286259. eCollection 2023.

ABSTRACT

BACKGROUND: Schools are high-risk settings for infectious disease transmission. Wastewater monitoring for infectious diseases has been used to identify and mitigate outbreaks in many near-source settings during the COVID-19 pandemic, including universities and hospitals but less is known about the technology when applied for school health protection. This study aimed to implement a wastewater surveillance system to detect SARS-CoV-2 and other public health markers from wastewater in schools in England.

METHODS: A total of 855 wastewater samples were collected from 16 schools (10 primary, 5 secondary and 1 post-16 and further education) over 10 months of school term time. Wastewater was analysed for SARS-CoV-2 genomic copies of N1 and E genes by RT-qPCR. A subset of wastewater samples was sent for genomic sequencing, enabling determination of the presence of SARS-CoV-2 and emergence of variant(s) contributing to COVID-19 infections within schools. In total, >280 microbial pathogens and >1200 AMR genes were screened using RT-qPCR and metagenomics to consider the utility of these additional targets to further inform on health threats within the schools.

RESULTS: We report on wastewater-based surveillance for COVID-19 within English primary, secondary and further education schools over a full academic year (October 2020 to July 2021). The highest positivity rate (80.4%) was observed in the week commencing 30th November 2020 during the emergence of the Alpha variant, indicating most schools contained people who were shedding the virus. There was high SARS-CoV-2 amplicon concentration (up to 9.2×106 GC/L) detected over the summer term (8th June – 6th July 2021) during Delta variant prevalence. The summer increase of SARS-CoV-2 in school wastewater was reflected in age-specific clinical COVID-19 cases. Alpha variant and Delta variant were identified in the wastewater by sequencing of samples collected from December to March and June to July, respectively. Lead/lag analysis between SARS-CoV-2 concentrations in school and WWTP data sets show a maximum correlation between the two-time series when school data are lagged by two weeks. Furthermore, wastewater sample enrichment coupled with metagenomic sequencing and rapid informatics enabled the detection of other clinically relevant viral and bacterial pathogens and AMR.

CONCLUSIONS: Passive wastewater monitoring surveillance in schools can identify cases of COVID-19. Samples can be sequenced to monitor for emerging and current variants of concern at the resolution of school catchments. Wastewater based monitoring for SARS-CoV-2 is a useful tool for SARS-CoV-2 passive surveillance and could be applied for case identification and containment, and mitigation in schools and other congregate settings with high risks of transmission. Wastewater monitoring enables public health authorities to develop targeted prevention and education programmes for hygiene measures within undertested communities across a broad range of use cases.

PMID:37252922 | DOI:10.1371/journal.pone.0286259

PLoS One. 2023 May 30;18(5):e0284696. doi: 10.1371/journal.pone.0284696. eCollection 2023.

ABSTRACT

INTRODUCTION: The construction industry in Nepal, which employs a significant proportion of the population, ranks as one of the largest industries in the country. Construction work is physically demanding and can be risky due to the use of heavy machinery and the presence of intense physical labor. However, the physical and mental health of construction workers in Nepal is often neglected. This study aimed to assess psychological distress (depression, anxiety, and stress symptoms) and its association with socio-demographic, lifestyle, and occupational factors among construction workers in Kavre district, Nepal.

METHODS: We conducted a cross-sectional study from 1st October 2019 to 15th January 2020 among 402 construction workers in Banepa, and Panauti municipalities of Kavre district, Nepal. We collected data with face-to-face interviews using a structured questionnaire consisting of a) socio-demographic characteristics; b) lifestyle and occupational characteristics; and c) depression, anxiety and stress symptoms. We collected data using electronic forms in KoboToolbox and imported them into R version 3.6.2 for statistical analysis. We present parametric numerical variables as mean and standard deviation, and categorical variables as percentage and frequency. The confidence interval around proportion was estimated with the Clopper-Pearson method. We applied univariate and multivariable logistic regression to determine factors associated with depression symptoms, anxiety, and stress. The result of logistic regression was presented as crude odds ratio, adjusted odds ratio (AOR), and their 95% confidence interval (CI).

RESULTS: The prevalence of depression, anxiety and stress symptoms were 17.1% (95%CI: 13.6-21.2), 19.2% (95%CI: 15.5-23.4) and 16.4% (95%CI: 12.9-20.4), respectively. In multivariable logistic regression analysis, depression symptom was positively associated with poor sleep quality (AOR = 3.51; 95%CI: 1.5-8.19; p-value: 0.004); stress symptom was positively associated with Brahmin ethnicity (AOR = 3.76; 95%CI:1.34-10.58; p-value: 0.012) and current smoking (AOR = 2.0; 95%CI: 1.11-3.82 p-value: 0.022). But anxiety symptoms were not associated with any of the variables.

CONCLUSIONS: The prevalence of depression, anxiety, and stress symptoms were high among construction workers. Developing evidence-based and appropriate community-based mental health prevention programs among laborers and construction workers is recommended.

PMID:37252920 | DOI:10.1371/journal.pone.0284696

PLOS Glob Public Health. 2023 May 30;3(5):e0001527. doi: 10.1371/journal.pgph.0001527. eCollection 2023.

ABSTRACT

Cryptosporidium and Giardia are major causes of diarrhoea globally, and two of the most notified infectious diseases in New Zealand. Diagnosis requires laboratory confirmation carried out mostly via antigen or microscopy-based techniques. However, these methods are increasingly being superseded by molecular techniques. Here we investigate the level of protozoa detection by molecular methods in campylobacteriosis cases missed through antigen-based assays and investigate different molecular testing protocols. We report findings from two observational studies; the first among 111 people during a Campylobacter outbreak and the second during normal surveillance activities among 158 people presenting with diarrhoea and a positive Campylobacter test, but negative Cryptosporidium and Giardia antigen-based test results. The molecular methods used for comparison were in-house end-point PCR tests targeting the gp60 gene for Cryptosporidium and gdh gene for Giardia. DNA extraction was performed with and without bead-beating and comparisons with commercial real-time quantitative (qPCR) were made using clinical Cryptosporidium positive sample dilutions down to 10-5. The Cryptosporidium prevalence was 9% (95% CI: 3-15; 10/111) and Giardia prevalence 21% (95% CI: 12-29; 23/111) in the 111 Campylobacter outbreak patients. The Cryptosporidium prevalence was 40% (95% CI: 32-48; 62/158) and Giardia prevalence 1.3% (95% CI: 0.2-4.5; 2/158) in the 158 routine surveillance samples. Sequencing identified Cryptosporidium hominis, C. parvum, and Giardia intestinalis assemblages A and B. We found no statistical difference in positive test results between samples using end-point PCR with or without bead-beating prior to DNA extraction, or between the in-house end-point PCR and qPCR. The qPCR Ct value was 36 (95% CI: 35-37) for 1 oocyst, suggesting a high limit of detection. In conclusion in surveillance and outbreak situations we found diagnostic serology testing underdiagnoses Cryptosporidium and Giardia coinfections in Campylobacter patients, suggesting the impact of protozoa infections may be underestimated through underdiagnosis using antigen-based assays.

PMID:37252910 | DOI:10.1371/journal.pgph.0001527

Natl Health Stat Report. 2023 May;(187):1-8.

ABSTRACT

Objective-This report provides a descriptive analysis of a sample of adult patients who visited the emergency department (ED) for nonfatal opioid overdose (NOO), using restricted-use 2016 National Hospital Care Survey data linked to the 2016-2017 National Death Index and the 2016-2017 Drug-Involved Mortality data from the National Center for Health Statistics.

PMID:37252888