Tag: pubmed

J Med Chem. 2024 Jul 17. doi: 10.1021/acs.jmedchem.4c00776. Online ahead of print.

ABSTRACT

30 covalent drugs were used to assess clearance (CL) prediction reliability in animals and humans. In animals, marked CL underprediction was observed using cryopreserved hepatocytes or liver microsomes (LMs) supplemented for cytochrome P450 activity. Improved quantitative performance was observed by combining metabolic stability data from LMs and liver S9 fractions, the latter supplemented with reduced glutathione for glutathione transferase activity. While human LMs provided reliable human CL predictions, prediction statistics were improved further by incorporating S9 stability data. CL predictions with allometric scaling were less robust compared to in vitro drug metabolism methods; the best results were obtained using the fu-corrected intercept model. Human volume of distribution (V_d) was well predicted using allometric scaling of animal pharmacokinetic data; the most reliable results were achieved using simple allometric scaling of unbound V_d values. These results provide a quantitative framework to guide appropriate method selection for human PK prediction with covalent drugs.

PMID:39018425 | DOI:10.1021/acs.jmedchem.4c00776

PLoS One. 2024 Jul 17;19(7):e0305600. doi: 10.1371/journal.pone.0305600. eCollection 2024.

ABSTRACT

Plants intimately coexist with diverse taxonomically structured microbial communities that influence host health and productivity. The coexistence of plant microbes in the phyllosphere benefits biodiversity maintenance, ecosystem function, and community stability. However, differences in community composition and network structures of phyllosphere epiphytic and endophytic fungi are widely unknown. Using Illumina Miseq sequencing of internal transcribed spacer (ITS) and 28S rRNA gene amplicons, we characterised the epiphytic and endophytic fungal communities associated with cashew phyllosphere (leaf, flower and fruit) from Kwale, Kilifi and Lamu counties in Kenya. The ITS and 28S rRNA gene sequences were clustered into 267 and 108 operational taxonomic units (OTUs) at 97% sequence similarity for both the epiphytes and endophytes. Phylum Ascomycota was abundant followed by Basidiomycota, while class Saccharomycetes was most dominant followed by Dothideomycetes. The major non-ascomycete fungi were associated only with class Tremellales. The fungal communities detected had notable ecological functions as saprotrophs and pathotrophs in class Saccharomyectes and Dothideomycetes. The community composition of epiphytic and endophytic fungi significantly differed between the phyllosphere organs which was statistically confirmed by the Analysis of Similarity test (ANOSIM Statistic R: 0.3273, for 28S rRNA gene and ANOSIM Statistic R: 0.3034 for ITS). The network analysis revealed that epiphytic and endophytic structures were more specialized, modular and had less connectance. Our results comprehensively describe the phyllosphere cashew-associated fungal community and serve as a foundation for understanding the host-specific microbial community structures among cashew trees.

PMID:39018319 | DOI:10.1371/journal.pone.0305600

PLOS Glob Public Health. 2024 Jul 17;4(7):e0003194. doi: 10.1371/journal.pgph.0003194. eCollection 2024.

ABSTRACT

The Covid-19 pandemic and associated restrictions have the potential to alter sexual risk behaviours for HIV acquisition with important implications for HIV prevention programmes in sub-Saharan Africa. To date, no large-scale data have been published to substantiate hypothesised changes in sexual risk behaviours. We used longitudinal survey data to assess the impact of Covid-19 on sexual risk behaviours in east Zimbabwe. Data on sexual behaviours in HIV-negative adults aged 15-54 years were collected in two rounds of a general population open-cohort survey conducted in Manicaland, Zimbabwe shortly before (July 2018 to December 2019; N = 7316) and several months into the Covid-19 epidemic (February to July 2021; N = 6356). Descriptive statistics and logistic regression models of serial cross-sectional and prospective cohort data were used to assess changes in sexual risk behaviours. The proportion of females aged 15-19 years reporting sexual debut declined from 29.7% before Covid-19 to 20.3% during Covid-19 (adjusted odds ratio (AOR) = 0.49, 95% confidence interval (95% CI), 0.38-0.63). Fewer sexually-active females reported multiple sexual partners during Covid-19 (3.35% versus 6.07%; AOR = 0.55, 95% CI, 0.43-0.72). No population-level changes in male behaviour between survey rounds were recorded but the cohort analysis revealed a complex pattern of behaviour change with HIV risk behaviours increasing for some individuals and decreasing for others. Overall HIV risk behaviours remained high in a sub-Saharan African population with a generalised HIV epidemic over a period of Covid-19 lockdowns when movements and social contacts were restricted.

PMID:39018312 | DOI:10.1371/journal.pgph.0003194

PLoS One. 2024 Jul 17;19(7):e0307284. doi: 10.1371/journal.pone.0307284. eCollection 2024.

ABSTRACT

With the overall objective of providing implication for clinical and research practices regarding the identification and measurement of modifiable predicting factors for return to work (RTW) in people with musculoskeletal disorders (MSDs) and common mental disorders (CMDs), this study 1) systematically examined and synthetized the research evidence available in the literature on the topic, and 2) critically evaluated the tools used to measure each identified factor. A systematic search of prognostic studies was conducted, considering four groups of keywords: 1) population (i.e., MSDs or CMDs), 2) study design (prospective), 3) modifiable factors, 4) outcomes of interest (i.e., RTW). Studies showing high risk of bias were eliminated. Tools used to measure prognostic factors were assessed using psychometric and usability criteria. From the 78 studies that met inclusion criteria, 19 (for MSDs) and 5 (for CMDs) factors reaching moderate or strong evidence were extracted. These factors included work accommodations, RTW expectations, job demands (physical), job demands (psychological), job strain, work ability, RTW self-efficacy, expectations of recovery, locus of control, referred pain (back pain), activities as assessed with disability questionnaires, pain catastrophizing, coping strategies, fears, illness behaviours, mental vitality, a positive health change, sleep quality, and participation. Measurement tools ranged from single-item tools to multi-item standardized questionnaires or subscales. The former generally showed low psychometric properties but excellent usability, whereas the later showed good to excellent psychometric properties and variable usability. The rigorous approach to the selection of eligible studies allowed the identification of a relatively small set of prognostic factors, but with a higher level of certainty. For each factor, the present tool assessment allows an informed choice to balance psychometric and usability criteria.

PMID:39018306 | DOI:10.1371/journal.pone.0307284

PLoS One. 2024 Jul 17;19(7):e0305295. doi: 10.1371/journal.pone.0305295. eCollection 2024.

ABSTRACT

INTRODUCTION: Evidence for the effect of neighbourhood food environment (NFE) exposures on diet in the UK is mixed, potentially due to exposure misclassification. This study used the first national COVID-19 lockdown in England as an opportunity to isolate the independent effects of the NFE exposure on food and drink purchasing, and assessed whether these varied by region.

METHODS: Transaction-level purchasing data for food and drink items for at-home (1,221 households) and out-of-home consumption (171 individuals) were available from the GB Kantar Fast Moving Consumer Goods Panel for London and the North of England. The study period included 23rd March to 10th May 2020 (‘lockdown’), and the same period in 2019 for comparison. NFE exposures included food outlet density and proximity, and NFE composition within a 1 km network buffer around the home. Associations were estimated for both years separately, adjusted for individual and household characteristics, population density and area deprivation. Interaction terms between region and exposures were explored.

RESULTS: There were no consistent patterns of association between NFE exposures and food and drink purchasing in either time period. In 2019, there was some evidence for a 1.4% decrease in energy purchased from ultra-processed foods for each additional 500 m in the distance to the nearest OOH outlet (IR 0.986, 95% CI 0.977 to 0.995, p = 0.020). In 2020, there was some evidence for a 1.8% reduction in total take-home energy for each additional chain supermarket per km2 in the neighbourhood (IR 0.982, 95% CI 0.969, 0.995, p = 0.045). Region-specific effects were observed in 2019 only.

DISCUSSION: Findings suggest that the differences in exposure to the NFE may not explain differences in the patterns or healthiness of grocery purchasing. Observed pre-pandemic region-specific effects allude to the importance of geographical context when designing research and policy. Future research may assess associations for those who relied on their NFE during lockdown.

PMID:39018304 | DOI:10.1371/journal.pone.0305295

PLoS One. 2024 Jul 17;19(7):e0306311. doi: 10.1371/journal.pone.0306311. eCollection 2024.

ABSTRACT

BACKGROUND: Despite the widespread use of humor in social interactions and the considerable literature on humor in multiple fields of study, the use of humor in parenting has received very little formal study. The purpose of this pilot study was to gather preliminary data on the use of humor in the raising of children.

MATERIALS AND METHODS: We developed and administered a 10-item survey to measure people’s experiences being raised with humor and their views regarding humor as a parenting tool. Responses were aggregated into Disagree, Indeterminate, and Agree, and analyzed using standard statistical methods.

RESULTS: Respondents (n = 312) predominantly identified as male (63.6%) and white (76.6%) and were (by selection) between the ages of 18-45 years old. The majority of participants reported that they: were raised by people who used humor in their parenting (55.2%); believe humor can be an effective parenting tool (71.8%) and in that capacity has more potential benefit than harm (63.3%); either use (or plan to use) humor in parenting their own children (61.8%); and would value a course on how to utilize humor in parenting (69.7%). Significant correlations were found between the use of humor and both i) the quality of respondents’ relationships with their parents and ii) assessments of how good a job their parents had done.

CONCLUSIONS: In this pilot study, respondents of childbearing/rearing age reported positive views about humor as a parenting tool.

PMID:39018300 | DOI:10.1371/journal.pone.0306311

PLoS One. 2024 Jul 17;19(7):e0305107. doi: 10.1371/journal.pone.0305107. eCollection 2024.

ABSTRACT

BACKGROUND: Sepsis is a life-threatening organ dysfunction due to a dysregulated host response to infection. Annually, sepsis leads to approx. 90.000 deaths in Germany. Risk factors include amongst others older age (>60), innate or acquired dysfunction of the immune system, and underlying chronic diseases of the lung, heart, liver, or kidneys. The manifestation of sepsis is a medical emergency, and patient outcomes depend on timely diagnosis and immediate treatment. In addition, vaccinations e.g., against pneumococci or influenza virus, are a highly effective public health tool to prevent the most common underlying infections that may lead to sepsis. However, a lack of public awareness for the relevance of vaccination and detecting sepsis as an emergency underlines the need for public health interventions that address these issues. SepWiss aims to evaluate the effects of a multimodal information campaign designed to address this lack of awareness among the risk population in Germany.

METHODS: SepWiss is an intervention at state level, consisting of a multimodal information campaign targeting risk groups in the German federal states of Berlin and Brandenburg (intervention region). Based on available evidence, various information formats were developed and implemented by outdoor advertising, social media, educational formats and through stakeholders’ platforms, starting in August 2021. The control region comprises of the remaining 14 German federal states. We will analyze vaccination coverage (primary outcome), and sepsis knowledge, the ability to detect sepsis as an emergency, and attitude towards vaccination (secondary outcomes) amongst the risk population in a controlled before-after comparison. The implementation is accompanied by a mixed-method process evaluation.

DISCUSSION: SepWiss is the first project of its kind to evaluate a complex multi-faceted evidence-based information campaign with regards to the topics of vaccination coverage, and the importance of sepsis detection and prevention for the most vulnerable populations in Germany. Results will be valuable for informing further nationwide campaigns.

TRIAL REGISTRATION: German Registry for Clinical Trials: DRKS00024475. Registered February 24th, 2021.

PMID:39018297 | DOI:10.1371/journal.pone.0305107

PLoS One. 2024 Jul 17;19(7):e0301940. doi: 10.1371/journal.pone.0301940. eCollection 2024.

ABSTRACT

Insula damage results in substantial impairments in facial emotion recognition. In particular, left hemispheric damage appears to be associated with poorer recognition of aversively rated facial expressions. Functional imaging can provide information on differences in the processing of these stimuli in patients with insula lesions when compared to healthy matched controls (HCs). We therefore investigated 17 patients with insula lesions in the chronic stage following stroke and 13 HCs using a passive-viewing task with pictures of facial expressions testing the blood oxygenation dependent (BOLD) effect in predefined regions of interest (ROIs). We expected a decrease in functional activation in an area modulating emotional response (left ventral striatum) but not in the facial recognition areas in the left inferior fusiform gyrus. Quantification of BOLD-response in ROIs but also voxel-based statistics confirmed this hypothesis. The voxel-based analysis demonstrated that the decrease in BOLD in the left ventral striatum was driven by left hemispheric damaged patients (n = 10). In our patient group, insula activation was strongly associated with the intensity rating of facial expressions. In conclusion, the combination of performance testing and functional imaging in patients following circumscribed brain damage is a challenging method for understanding emotion processing in the human brain.

PMID:39018294 | DOI:10.1371/journal.pone.0301940

PLoS One. 2024 Jul 17;19(7):e0305482. doi: 10.1371/journal.pone.0305482. eCollection 2024.

ABSTRACT

This paper investigates the effect of Chinese outward foreign direct investment (FDI) on youth unemployment in sub-Saharan Africa (SSA) by using a modified labour demand model to identify the investment sources that are helpful for reducing youth unemployment in the region. The model is applied to a panel of 42 countries for the period 2003-2021 using random-effect, and generalized method of moment (GMM) estimators for robustness check. Our results suggest that Chinese FDI has direct short-term reducing effect on youth unemployment in SSA. The direction of China’s capital investment to infrastructure development and other labour-intensive activities leads to immediate reduction in youth unemployment. However, overtime, due to absence of linkages with domestic firms, and thus lack of demand effects, Chinese FDI becomes insignificant for employment creation. Our results also indicate that Other FDI does not lead to significant reduction in youth unemployment both currently and overtime. Our analysis gives partial support to the argument that the impact of Chinese FDI may differ from those of developed countries. Finally, we could not find evidence that the effect of FDI on employment depends on host country human capital and institutional quality. Several specifications of the empirical model are tested, and explanations are provided for the results. Policy implications are highlighted, especially the need to attract more job absorbing FDI and improve domestic absorptive capacity.

PMID:39018290 | DOI:10.1371/journal.pone.0305482

JMIR Res Protoc. 2024 Jul 17;13:e56749. doi: 10.2196/56749.

ABSTRACT

BACKGROUND: Integration of mobile health data collection methods into cohort studies enables the collection of intensive longitudinal information, which gives deeper insights into individuals’ health and lifestyle behavioral patterns over time, as compared to traditional cohort methods with less frequent data collection. These findings can then fill the gaps that remain in understanding how various lifestyle behaviors interact as students graduate from university and seek employment (student-to-work life transition), where the inability to adapt quickly to a changing environment greatly affects the mental well-being of young adults.

OBJECTIVE: This paper aims to provide an overview of the study methodology and baseline characteristics of participants in Health@NUS, a longitudinal study leveraging mobile health to examine the trajectories of health behaviors, physical health, and well-being, and their diverse determinants, for young adults during the student-to-work life transition.

METHODS: University students were recruited between August 2020 and June 2022 in Singapore. Participants would complete biometric assessments and questionnaires at 3 time points (baseline, 12-, and 24-month follow-up visits) and use a Fitbit smartwatch and smartphone app to continuously collect physical activity, sedentary behavior, sleep, and dietary data over the 2 years. Additionally, up to 12 two-week-long bursts of app-based ecological momentary surveys capturing lifestyle behaviors and well-being would be sent out among the 3 time points.

RESULTS: Interested participants (n=1556) were screened for eligibility, and 776 participants were enrolled in the study between August 2020 and June 2022. Participants were mostly female (441/776, 56.8%), of Chinese ethnicity (741/776, 92%), undergraduate students (759/776, 97.8%), and had a mean BMI of 21.9 (SD 3.3) kg/m², and a mean age of 22.7 (SD 1.7) years. A substantial proportion were overweight (202/776, 26.1%) or obese (42/776, 5.4%), had indicated poor mental well-being (World Health Organization-5 Well-Being Index ≤50; 291/776, 37.7%), or were at higher risk for psychological distress (Kessler Psychological Distress Scale ≥13; 109/776, 14.1%).

CONCLUSIONS: The findings from this study will provide detailed insights into the determinants and trajectories of health behaviors, health, and well-being during the student-to-work life transition experienced by young adults.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05154227; https://clinicaltrials.gov/study/NCT05154227.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56749.

PMID:39018103 | DOI:10.2196/56749