Nevin Manimala

PLoS One. 2022 Jan 28;17(1):e0263192. doi: 10.1371/journal.pone.0263192. eCollection 2022.

ABSTRACT

Non-aversive handling is a well-documented refinement measure for improving rodent welfare. Because maternal stress is related to reduced productivity, we hypothesized that welfare benefits associated with non-aversive handling would translate to higher production and fewer litters lost in a laboratory mouse breeding colony. We performed a randomized controlled trial to examine the effects of a standard method of handling (tail-lift with forceps) versus non-aversive handling with transfer tunnels (‘tunnel-handled’) on breeding performance in 59 C57BL/6J mouse pairs. Intervention assignments could not be concealed from technicians, but were concealed from assessors and data analyst. An operationally significant effect of tunnel-handling (large enough differences to warrant programmatic change) was defined before study initiation as a 5% increase in productivity, or one extra pup over the reproductive lifetime of each pair. Pairs were randomly allocated to handling intervention and cage rack location, and monitored over an entire 6-month breeding cycle. For each group, we measured number of pups born and weaned, and number of entire litters lost prior to weaning. Differences between transfer methods were estimated by two-level hierarchical mixed models adjusted for parental effects and parity. Compared to tail-lift mice, tunnel-handled mice averaged one extra pup per pair born (+1.0; 95% CI 0.9, 1.1; P = 0.41) and weaned (+1.1, 95% CI 0.9, 1.2; P = 0.33). More tunnel-handled pairs successfully weaned all litters produced (13/29 pairs, 45% vs 4/30 pairs, 13%; P = 0.015), averaged fewer litter losses prior to weaning (11/29 pairs [38%] vs 26/30 pairs [87%]; P <0.001), and had a 20% lower risk of recurrent litter loss. The increase in numbers of pups produced and weaned with tunnel handling met threshold requirement for operational significance. These data and projected cost savings persuaded management to incorporate tunnel handling as standard of care across the institution. These data also suggest that overlooked husbandry practices such as cage transfer may be major confounders in studies of mouse models.

PMID:35089969 | DOI:10.1371/journal.pone.0263192

PLoS One. 2022 Jan 28;17(1):e0262987. doi: 10.1371/journal.pone.0262987. eCollection 2022.

ABSTRACT

BACKGROUND: Metformin is prescribed to women with polycystic ovary syndrome (PCOS) to prevent pregnancy complications. Children exposed to metformin vs. placebo in utero, have increased head circumference at birth and are more overweight and obese at 8 years of age. Also, maternal PCOS-status seems to alter the long-term cardio-metabolic health of offspring. We hypothesized that the long-term effects of metformin-exposure and/or maternal PCOS may be mediated by circulatory adaptations during fetal life.

MATERIAL AND METHODS: This is a sub-study of a larger double-blinded, placebo-controlled trial, where women with PCOS were randomized to metformin (2g/day) or placebo in pregnancy, a total of 487 women. A sub-group of participants (N = 58) took part in this sub-study and had an extended ultrasound examination at gestational week 32, including blood flow velocity and diameter measurements of the umbilical vein (UV), the ductus venosus (DV) and the portal vein (PV). Blood flow volume was calculated and adjusted for estimated fetal weight (EFW) (normalized flow). Metformin exposed fetuses were compared to placebo exposed fetuses. Fetuses of mothers with PCOS (metformin [n = 30] and placebo [n = 28]) were compared to a low-risk reference population (N = 160) by z-score statistics.

RESULTS: There was no difference in fetal liver flow between metformin vs. placebo-exposed fetuses. Fetuses of mothers with PCOS had higher EFW (0.63 [95% CI 0.44-0.83] p<0.001), lower normalized UV, DV, PV, and lower total venous liver blood flows than the reference population.

CONCLUSION: Metformin during pregnancy did not affect fetal liver blood-flow. In our population, maternal PCOS-status was associated with reduced total venous liver blood-flow, which may explain altered growth and metabolism later in life.

PMID:35089960 | DOI:10.1371/journal.pone.0262987

PLoS One. 2022 Jan 28;17(1):e0262743. doi: 10.1371/journal.pone.0262743. eCollection 2022.

ABSTRACT

The Indonesian government launched various programs to handle stunting cases, including village funds. This paper examined the effects of village fund programs and village apparatuses’ capacities to combat stunting based on aggregate data at the district level in Indonesia. Using descriptive data analysis and fixed effect panel regression, we observed that village fund programs could significantly reduce Indonesia’s stunting prevalence, especially outside Java. It also revealed that the increasing education of regional leaders does not necessarily positively impact leaders’ skills in handling stunting. At the same time, the number of village officials has a statistically significant influence on reducing stunting prevalence. It advised that the village budget fund can support national priorities in tackling the prevalence of stunting. Furthermore, it is essential to build the capacity of the village head for increasing awareness of health activities, especially early prevention of stunting, in addition to an adequate number of officials.

PMID:35089957 | DOI:10.1371/journal.pone.0262743

PLoS One. 2022 Jan 28;17(1):e0262731. doi: 10.1371/journal.pone.0262731. eCollection 2022.

ABSTRACT

Appropriate antibiotic prescription contributes to reducing bacterial resistance; therefore, it is critical to provide training regarding this challenge. The objective of this study was to develop a virtual learning environment for antibiotic prescription and to determine its impact on dentists’ awareness, attitudes, and intention to practice. First, the learning content on multimedia resources was developed and distributed into three challenges that participants had to overcome. Then, a quasi-experimental study was performed in which the virtual learning environment was implemented on dentists from seven Colombian cities. The median of correct answers and the levels of awareness, attitudes, and intention to practice were compared before, immediately after, and 6-months post-intervention. Wilcoxon signed-rank and McNemar’s tests were used to determine the differences. A total of 206 participants who finished the virtual learning environment activities exhibited a favorable and statistically significant impact on the median of correct answers of awareness (p < 0.001), attitudes (p < 0.001), and intention to practice (p = 0.042). A significant increase occurred in the number of participants with a high level of awareness (p < 0.001) and a non-significant increase in participants with high levels of attitudes (p = 0.230) and intention to practice (p = 0.286). At 6 months, the positive effect on the median of correct answers on awareness and intention to practice persisted (p < 0.001); however, this was not evident for attitudes (p = 0.105). Moreover, there was a significant decrease in the number of participants who showed low levels of awareness (p = 0.019) and a slight increase in those with high levels of the same component (p = 0.161). The use of a virtual learning environment designed for dentists contributed to a rapid improvement in awareness and intention to practice antibiotic prescription; however, their attitudes and information retention need reinforcement.

PMID:35089952 | DOI:10.1371/journal.pone.0262731

PLoS One. 2022 Jan 28;17(1):e0248171. doi: 10.1371/journal.pone.0248171. eCollection 2022.

ABSTRACT

Vehicle-tree collisions are the most common type of road crash with fixed obstacle in Czech Republic. Based on the literature review and using real world in-depth crash data, this paper aims to define factors, which significantly influence the injury severity of single vehicle-tree crashes. In-depth data provide a comprehensive view to the failure on the system infrastructure-human-vehicle related to crash, the in-depth crash database include very detailed information related to infrastructure, vehicle, human failure and crash participants characteristics and their medical condition and also crash reconstruction. Multinomial logistic regression and generalized linear mixed model were used to determine the individual effect of each predictor. The statistically significant variables were the day period, trunk diameter and impact speed. Using multinomial logistic regression shows also vehicle age as statistically significant. Obtained results can help to efficiently direct countermeasures not only on the road infrastructure-e.g. speed reduction in selected locations with specified tree character. However, the emphasis should be also focused on driver behaviour.

PMID:35089932 | DOI:10.1371/journal.pone.0248171

PLoS One. 2022 Jan 28;17(1):e0261500. doi: 10.1371/journal.pone.0261500. eCollection 2022.

ABSTRACT

INTRODUCTION: People who inject drugs (PWID) in Sub-Saharan Africa have limited access to comprehensive HIV services. While it is important to inform programming, knowledge about factors influencing access to comprehensive HIV services is scarce. We assessed the proportions of PWID with access to HIV prevention services and associated socio-cognitive factors in Tanzania.

METHODS: A cross-sectional survey was conducted among PWID between October and December 2017 in Dar es Salaam, Tanzania. Data on access to HIV prevention services, demographics and selected socio-cognitive factors were collected through structured face-to-face interviews. Weighted descriptive and forward selection multivariable logistics regression analyses were done to assess independent associations between HIV prevention services and predictors of interest. The results were two tailed and a p-value of less than 0.05 was considered statistically significant.

RESULTS: The study included 611 PWID (males: 94.4%) with a median age of 34 years (Interquartile Range (IQR), 29-38). A large majority of participants reported to have access to condoms (87.8%), sterile needles/syringes (72.8%) and ever tested for HIV (66.0%). About half (52.0%) reported to have used condoms in the past one month and about a third (28.5%) accessed a peer educator. The odds of testing for HIV decreased among participants who perceived their HIV risk to be high (aOR = 0.29; 95%CI: 0.17-0.49) and those experienced sexual violence (aOR = 0.60; 95%CI 0.37-0.98). However, the odds of testing for HIV increased among participants with secondary level of education (aOR = 2.16; 95%CI: 1.06-5.55), and those who reported having correct comprehensive HIV knowledge (CCHK) (aOR = 1.63; 95%CI 1.12-2.41). The odds of access to condoms increased among females (aOR = 2.23; 95%CI: 1.04-5.02) but decreased among participants with secondary level of education (aOR = 0.41; 95%CI: 0.19-0.84), an income of >TZS 200,000 (aOR = 0.39; 95%CI: 0.23-0.66) and those who perceived their HIV risk to be high (aOR = 0.13; 95%CI: 0.03-0.36). The odds of access to peer educators was higher among participants with primary (aOR = 1.61; 95%CI: 1.01-2.26), and secondary (aOR = 2.71; 95%CI: 1.39-5.33) levels of education. The odds of access to sterile needle and syringe decreased among participants who perceived their HIV risk to be high (aOR = 0.11;95%CI 0.05-0.22), and low-medium (aOR = 0.25;95%CI 0.11-0.52) but increased among those with primary level of education (aOR = 1.72;95%CI 1.06-2.78).

CONCLUSION: Access to condom, HIV testing, sterile needles and syringes were relatively high among PWID. However, condom use and access to peer educators was relatively low. HIV knowledge and risk perception, gender, education, and sexual violence influenced access to HIV prevention services. There is an urgent need to address the identified socio-cognitive factors and scale up all aspects of HIV prevention services to fast-track attainment of the 2025 UNAIDS goals and ending the HIV epidemic.

PMID:35089928 | DOI:10.1371/journal.pone.0261500

PLoS One. 2022 Jan 28;17(1):e0261691. doi: 10.1371/journal.pone.0261691. eCollection 2022.

ABSTRACT

Conduct Disorder (CD) is an impairing psychiatric disorder of childhood and adolescence characterized by aggressive and dissocial behavior. Environmental factors such as maternal smoking during pregnancy, socio-economic status, trauma, or early life stress are associated with CD. Although the number of females with CD is rising in Western societies, CD is under-researched in female cohorts. We aimed at exploring the epigenetic signature of females with CD and its relation to psychosocial and environmental risk factors. We performed HpaII sensitive genome-wide methylation sequencing of 49 CD girls and 50 matched typically developing controls and linear regression models to identify differentially methylated CpG loci (tags) and regions. Significant tags and regions were mapped to the respective genes and tested for enrichment in pathways and brain developmental processes. Finally, epigenetic signatures were tested as mediators for CD-associated risk factors. We identified a 12% increased methylation 5′ of the neurite modulator SLITRK5 (FDR = 0.0046) in cases within a glucocorticoid receptor binding site. Functionally, methylation positively correlated with gene expression in lymphoblastoid cell lines. At systems-level, genes (uncorr. P < 0.01) were associated with development of neurons, neurite outgrowth or neuronal developmental processes. At gene expression level, the associated gene-networks are activated perinatally and during early childhood in neocortical regions, thalamus and striatum, and expressed in amygdala and hippocampus. Specifically, the epigenetic signatures of the gene network activated in the thalamus during early childhood correlated with the effect of parental education on CD status possibly mediating its protective effect. The differential methylation patterns identified in females with CD are likely to affect genes that are expressed in brain regions previously indicated in CD. We provide suggestive evidence that protective effects are likely mediated by epigenetic mechanisms impairing specific brain developmental networks and therefore exerting a long-term effect on neural functions in CD. Our results are exploratory and thus, further replication is needed.

PMID:35089926 | DOI:10.1371/journal.pone.0261691

PLoS Comput Biol. 2022 Jan 28;18(1):e1009812. doi: 10.1371/journal.pcbi.1009812. Online ahead of print.

ABSTRACT

Cell intercalation is a key cell behaviour of morphogenesis and wound healing, where local cell neighbour exchanges can cause dramatic tissue deformations such as body axis extension. Substantial experimental work has identified the key molecular players facilitating intercalation, but there remains a lack of consensus and understanding of their physical roles. Existing biophysical models that represent cell-cell contacts with single edges cannot study cell neighbour exchange as a continuous process, where neighbouring cell cortices must uncouple. Here, we develop an Apposed-Cortex Adhesion Model (ACAM) to understand active cell intercalation behaviours in the context of a 2D epithelial tissue. The junctional actomyosin cortex of every cell is modelled as a continuous viscoelastic rope-loop, explicitly representing cortices facing each other at bicellular junctions and the adhesion molecules that couple them. The model parameters relate directly to the properties of the key subcellular players that drive dynamics, providing a multi-scale understanding of cell behaviours. We show that active cell neighbour exchanges can be driven by purely junctional mechanisms. Active contractility and cortical turnover in a single bicellular junction are sufficient to shrink and remove a junction. Next, a new, orthogonal junction extends passively. The ACAM reveals how the turnover of adhesion molecules regulates tension transmission and junction deformation rates by controlling slippage between apposed cell cortices. The model additionally predicts that rosettes, which form when a vertex becomes common to many cells, are more likely to occur in actively intercalating tissues with strong friction from adhesion molecules.

PMID:35089922 | DOI:10.1371/journal.pcbi.1009812

PLoS Negl Trop Dis. 2022 Jan 28;16(1):e0010103. doi: 10.1371/journal.pntd.0010103. eCollection 2022 Jan.

ABSTRACT

BACKGROUND: Mass vaccination campaigns have significantly reduced the COVID-19 burden. However, vaccine hesitancy has posed significant global concerns. The purpose of this study was to determine the characteristics that influence perceptions of COVID-19 vaccine efficacy, acceptability, hesitancy and decision making to take vaccine among general adult populations in a variety of socioeconomic and cultural contexts.

METHODS: Using a snowball sampling approach, we conducted an online cross-sectional study in 20 countries across four continents from February to May 2021.

RESULTS: A total of 10,477 participants were included in the analyses with a mean age of 36±14.3 years. The findings revealed the prevalence of perceptions towards COVID-19 vaccine’s effectiveness (78.8%), acceptance (81.8%), hesitancy (47.2%), and drivers of vaccination decision-making (convenience [73.3%], health providers’ advice [81.8%], and costs [57.0%]). The county-wise distribution included effectiveness (67.8-95.9%; 67.8% in Egypt to 95.9% in Malaysia), acceptance (64.7-96.0%; 64.7% in Australia to 96.0% in Malaysia), hesitancy (31.5-86.0%; 31.5% in Egypt to 86.0% in Vietnam), convenience (49.7-95.7%; 49.7% in Austria to 95.7% in Malaysia), advice (66.1-97.3%; 66.1% in Austria to 97.3% in Malaysia), and costs (16.0-91.3%; 16.0% in Vietnam to 91.3% in Malaysia). In multivariable regression analysis, several socio-demographic characteristics were identified as associated factors of outcome variables including, i) vaccine effectiveness: younger age, male, urban residence, higher education, and higher income; ii) acceptance: younger age, male, urban residence, higher education, married, and higher income; and iii) hesitancy: male, higher education, employed, unmarried, and lower income. Likewise, the factors associated with vaccination decision-making including i) convenience: younger age, urban residence, higher education, married, and lower income; ii) advice: younger age, urban residence, higher education, unemployed/student, married, and medium income; and iii) costs: younger age, higher education, unemployed/student, and lower income.

CONCLUSIONS: Most participants believed that vaccination would effectively control and prevent COVID-19, and they would take vaccinations upon availability. Determinant factors found in this study are critical and should be considered as essential elements in developing COVID-19 vaccination campaigns to boost vaccination uptake in the populations.

PMID:35089917 | DOI:10.1371/journal.pntd.0010103

PLoS Comput Biol. 2022 Jan 28;18(1):e1009799. doi: 10.1371/journal.pcbi.1009799. Online ahead of print.

ABSTRACT

One of the main goals of current systems neuroscience is to understand how neuronal populations integrate sensory information to inform behavior. However, estimating stimulus or behavioral information that is encoded in high-dimensional neuronal populations is challenging. We propose a method based on parametric copulas which allows modeling joint distributions of neuronal and behavioral variables characterized by different statistics and timescales. To account for temporal or spatial changes in dependencies between variables, we model varying copula parameters by means of Gaussian Processes (GP). We validate the resulting Copula-GP framework on synthetic data and on neuronal and behavioral recordings obtained in awake mice. We show that the use of a parametric description of the high-dimensional dependence structure in our method provides better accuracy in mutual information estimation in higher dimensions compared to other non-parametric methods. Moreover, by quantifying the redundancy between neuronal and behavioral variables, our model exposed the location of the reward zone in an unsupervised manner (i.e., without using any explicit cues about the task structure). These results demonstrate that the Copula-GP framework is particularly useful for the analysis of complex multidimensional relationships between neuronal, sensory and behavioral variables.

PMID:35089913 | DOI:10.1371/journal.pcbi.1009799