A latent class approach to understanding experiences of bullying victimization among youth in four low-resource settings

Background. Bullying victimization is a very common form of aggression experienced by school-aged youth and a risk factor for poor psychosocial adjustment. Yet there is a lack of victimization research in low and middle income countries (LMIC), where cultural and contextual factors may influence victimization dynamics. The goal of this current research was to examine experiences and outcomes of peer victimization among adolescents in four LMIC. Methods. Analyses included data on 3,536 youth (aged 15) in the Young Lives study in Ethiopia, India, Peru, and Vietnam, who reported exposure to nine peer victimization behaviors as well as information on emotional difficulties, wellbeing, and risk behaviors. We examined prevalence of victimizing behaviors across countries and used Hurdle modelling to evaluate associations between victimization and sex, community context, and school enrollment. We then used latent class analysis (LCA) to identify patterns of victimization and psychosocial adjustment correlates of latent class. Results. Physical victimization was substantially higher in India than elsewhere. Higher direct victimization among boys was observed everywhere but Peru. There were few sex differences in relational victimization. We found little variation in exposure by school status. Data supported a 2-class LCA model in Peru, 3-class in Ethiopia and Vietnam, and 4-class in India. Unlike the ordered classes produced elsewhere, the India model also produced two classes uniquely characterized by direct and indirect victimization. Boys were more likely than girls to be in the highly victimized class in Ethiopia and India. Urban contexts were associated with increased risk in Ethiopia and Peru, and decreased risk in India and Vietnam. Emotional difficulties and alcohol use were strongly associated with victimization; more modest associations with wellbeing outcomes showed similar trends. Discussion. Notable differences in victimization patterns highlight the need to better understand these experiences in LMIC, where factors such as forms of behavior, who is at risk, and where victimization occurs may vary. LCA patterns suggest that targeted youth are likely to experience multiple forms of victimization. Strong and consistent associations between victimization and psychosocial adjustment across countries demonstrate the need to recognize peer victimization as a serious public health issue in LMIC

Multiplex-Ready PCR: A new method for multiplexed SSR and SNP genotyping

© 2008 Hayden et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background Microsatellite (SSR) and single nucleotide polymorphism (SNP) markers are widely used in plant breeding and genomic research. Thus, methods to improve the speed and efficiency of SSR and SNP genotyping are highly desirable. Here we describe a new method for multiplex PCR that facilitates fluorescence-based SSR genotyping and the multiplexed preparation of DNA templates for SNP assays. Results We show that multiplex-ready PCR can achieve a high (92%) success rate for the amplification of published sequences under standardised reaction conditions, with a PCR specificity comparable to that of conventional PCR methods. We also demonstrate that multiplex-ready PCR supports an improved level of multiplexing in plant genomes of varying size and ploidy, without the need to carefully optimize assay conditions. Several advantages of multiplex-ready PCR for SSR and SNP genotyping are demonstrated and discussed. These include the uniform amplification of target sequences within multiplexed reactions and between independent assays, and the ability to label amplicons during PCR with specialised moieties such fluorescent dyes and biotin. Conclusion Multiplex-ready PCR provides several technological advantages that can facilitate fluorescence-based SSR genotyping and the multiplexed preparation of DNA templates for SNP assays. These advantages can be captured at several points in the genotyping process, and offer considerable cost and labour savings. Multiplex-ready PCR is broadly applicable to plant genomics and marker assisted breeding, and should be transferable to any animal or plant species.Matthew J Hayden, Thao M Nguyen, Amanda Waterman and Kenneth J Chalmer

Promoting Community Health Research Partnerships Through a Small Grants Program: Processes and Lessons Learned

While there are multiple ways to engage communities in health research, one approach is through partnership-based research in which community representatives are involved as intentional partners in the research process, from conceptualization and co-creation to implementation, analysis, interpretation, and dissemination. However, there remain numerous challenges to supporting and sustaining such partnerships. Since its launch in 2019, the integrated Translational Health Research Institute of Virginia (iTHRIV) has sought to foster community engaged health research among its four research/clinical institutions through a community partnership-based grant program. Over five funding cycles, iTHRIV has awarded 14 one-year research grants addressing topics such as opioid use disorder, cancer, hepatitis C and autism. Each funding cycle has provided valuable experience and feedback toward iterative program refinements. Key lessons have included: 1) the Request For Proposals (RFP) must be very clear and community-vetted; 2) transparency regarding administrative burden required for compliance is critical to inform cost-benefit decisions; 3) giving different modes of communication, adequate and creative marketing of the RFP is necessary; 4) establishing a centralized program officer for all grantees facilitated post-award procedural navigation; 5) one year is insufficient to carry out most studies involving human subjects. Additionally, while the program anecdotally promoted collaborative partnerships, the true impact may be difficult to evaluate

Effects of Surface Geology on Seismic Ground Motion Deduced from Ambient-Noise Measurements in the Town of Avellino, Irpinia Region (Italy)

The effects of surface geology on ground motion provide an important tool in seismic hazard studies. It is well known that the presence of soft sediments can cause amplification of the ground motion at the surface, particularly when there is a sharp impedance contrast at shallow depth. The town of Avellino is located in an area characterised by high seismicity in Italy, about 30 km from the epicentre of the 23 November 1980, Irpinia earthquake (M = 6.9). No earthquake recordings are available in the area. The local geology is characterised by strong heterogeneity, with impedance contrasts at depth. We present the results from seismic noise measurements carried out in the urban area of Avellino to evaluate the effects of local geology on the seismic ground motion. We computed the horizontal-to-vertical (H/V) noise spectral ratios at 16 selected sites in this urban area for which drilling data are available within the first 40 m of depth. A Rayleigh wave inversion technique using the peak frequencies of the noise H/V spectral ratios is then presented for estimating Vs models, assuming that the thicknesses of the shallow soil layers are known. The results show a good correspondence between experimental and theoretical peak frequencies, which are interpreted in terms of sediment resonance. For one site, which is characterised by a broad peak in the horizontal-to-vertical spectral-ratio curve, simple one-dimensional modelling is not representative of the resonance effects. Consistent variations in peak amplitudes are seen among the sites. A site classification based on shear-wave velocity characteristics, in terms of Vs30, cannot explain these data. The differences observed are better correlated to the impedance contrast between the sediments and basement. A more detailed investigation of the physical parameters of the subsoil structure, together with earthquake data, are desirable for future research, to confirm these data in terms of site response

Intermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice

BACKGROUND:Intermittent severe energy restriction is popular for weight management. To investigate whether intermittent moderate energy restriction may improve this approach by enhancing weight loss efficiency, we conducted a study in mice, where energy intake can be controlled. METHODS:Male C57/Bl6 mice that had been rendered obese by an ad libitum diet high in fat and sugar for 22 weeks were then fed one of two energy-restricted normal chow diets for a 12-week weight loss phase. The continuous diet (CD) provided 82% of the energy intake of age-matched ad libitum chow-fed controls. The intermittent diet (ID) provided cycles of 82% of control intake for 5-6 consecutive days, and ad libitum intake for 1-3 days. Weight loss efficiency during this phase was calculated as (total weight change) ÷ [(total energy intake of mice on CD or ID)-(total average energy intake of controls)]. Subsets of mice then underwent a 3-week weight regain phase involving ad libitum re-feeding. RESULTS:Mice on the ID showed transient hyperphagia relative to controls during each 1-3-day ad libitum feeding period, and overall ate significantly more than CD mice (91.1±1.0 versus 82.2±0.5% of control intake respectively, n = 10, P<0.05). There were no significant differences between CD and ID groups at the end of the weight loss or weight regain phases with respect to body weight, fat mass, circulating glucose or insulin concentrations, or the insulin resistance index. Weight loss efficiency was significantly greater with ID than with CD (0.042±0.007 versus 0.018±0.001 g/kJ, n = 10, P<0.01). Mice on the CD exhibited significantly greater hypothalamic mRNA expression of proopiomelanocortin (POMC) relative to ID and control mice, with no differences in neuropeptide Y or agouti-related peptide mRNA expression between energy-restricted groups. CONCLUSION:Intermittent moderate energy restriction may offer an advantage over continuous moderate energy restriction, because it induces significantly greater weight loss relative to energy deficit in mice

Maternal mental health priorities, help-seeking behaviors, and resources in post-conflict settings: a qualitative study in eastern Uganda.

BACKGROUND: Limited knowledge exists to inform the selection and introduction of locally relevant, feasible, and effective mental health interventions in diverse socio-cultural contexts and health systems. We examined stakeholders\u27 perspectives on mental health-related priorities, help-seeking behaviors, and existing resources to guide the development of a maternal mental health component for integration into non-specialized care in Soroti, eastern Uganda. METHODS: We employed rapid ethnographic methods (free listing and ranking; semi-structured interviews; key informant interviews and pile sorting) with community health workers (n = 24), primary health workers (n = 26), perinatal women (n = 24), traditional and religious healers (n = 10), and mental health specialists (n = 9). Interviews were conducted by trained Ateso-speaking interviewers. Two independent teams conducted analyses of interview transcripts following an inductive and thematic approach. Smith\u27s Salience Index was used for analysis of free listing data. RESULTS: When asked about common reasons for visiting health clinics, the most salient responses were malaria, general postnatal care, and husbands being absent. Amongst the free listed items that were identified as mental health problems, the three highest ranked concerns were adeka na aomisio (sickness of thoughts); ipum (epilepsy), and emalaria (malaria). The terms epilepsy and malaria were used in ways that reflected both biomedical and cultural concepts of distress. Sickness of thoughts appeared to overlap substantially with major depression as described in international classification, and was perceived to be caused by unsupportive husbands, intimate partner violence, chronic poverty, and physical illnesses. Reported help-seeking for sickness of thoughts included turning to family and community members for support and consultation, followed by traditional or religious healers and health centers if the problem persisted. CONCLUSION: Our findings add to existing literature that describes \u27thinking too much\u27 idioms as cultural concepts of distress with roots in social adversity. In addition to making feasible and effective treatment available, our findings indicate the importance of prevention strategies that address the social determinants of psychological distress for perinatal women in post-conflict low-resource contexts

Evidence for Alteration of Gene Regulatory Networks through MicroRNAs of the HIV-Infected Brain: Novel Analysis of Retrospective Cases

HIV infection disturbs the central nervous system (CNS) through inflammation and glial activation. Evidence suggests roles for microRNA (miRNA) in host defense and neuronal homeostasis, though little is known about miRNAs' role in HIV CNS infection. MiRNAs are non-coding RNAs that regulate gene translation through post-transcriptional mechanisms. Messenger-RNA profiling alone is insufficient to elucidate the dynamic dance of molecular expression of the genome. We sought to clarify RNA alterations in the frontal cortex (FC) of HIV-infected individuals and those concurrently infected and diagnosed with major depressive disorder (MDD). This report is the first published study of large-scale miRNA profiling from human HIV-infected FC. The goals of this study were to: 1. Identify changes in miRNA expression that occurred in the frontal cortex (FC) of HIV individuals, 2. Determine whether miRNA expression profiles of the FC could differentiate HIV from HIV/MDD, and 3. Adapt a method to meaningfully integrate gene expression data and miRNA expression data in clinical samples. We isolated RNA from the FC (n = 3) of three separate groups (uninfected controls, HIV, and HIV/MDD) and then pooled the RNA within each group for use in large-scale miRNA profiling. RNA from HIV and HIV/MDD patients (n = 4 per group) were also used for non-pooled mRNA analysis on Affymetrix U133 Plus 2.0 arrays. We then utilized a method for integrating the two datasets in a Target Bias Analysis. We found miRNAs of three types: A) Those with many dysregulated mRNA targets of less stringent statistical significance, B) Fewer dysregulated target-genes of highly stringent statistical significance, and C) unclear bias. In HIV/MDD, more miRNAs were downregulated than in HIV alone. Specific miRNA families at targeted chromosomal loci were dysregulated. The dysregulated miRNAs clustered on Chromosomes 14, 17, 19, and X. A small subset of dysregulated genes had many 3′ untranslated region (3′UTR) target-sites for dysregulated miRNAs. We provide evidence that certain miRNAs serve as key elements in gene regulatory networks in HIV-infected FC and may be implicated in neurobehavioral disorder. Finally, our data indicates that some genes may serve as hubs of miRNA activity

Canonical Nlrp3 Inflammasome Links Systemic Low-Grade Inflammation to Functional Decline in Aging

SummaryDespite a wealth of clinical data showing an association between inflammation and degenerative disorders in the elderly, the immune sensors that causally link systemic inflammation to aging remain unclear. Here we detail a mechanism by which the Nlrp3 inflammasome controls systemic low-grade age-related “sterile” inflammation in both periphery and brain independently of the noncanonical caspase-11 inflammasome. Ablation of Nlrp3 inflammasome protected mice from age-related increases in the innate immune activation, alterations in CNS transcriptome, and astrogliosis. Consistent with the hypothesis that systemic low-grade inflammation promotes age-related degenerative changes, the deficient Nlrp3 inflammasome-mediated caspase-1 activity improved glycemic control and attenuated bone loss and thymic demise. Notably, IL-1 mediated only Nlrp3 inflammasome-dependent improvement in cognitive function and motor performance in aged mice. These studies reveal Nlrp3 inflammasome as an upstream target that controls age-related inflammation and offer an innovative therapeutic strategy to lower Nlrp3 activity to delay multiple age-related chronic diseases

Critical contributions of protein cargos to the functions of macrophage‑derived extracellular vesicles

Background Macrophages are highly plastic innate immune cells that play key roles in host defense, tissue repair, and homeostasis maintenance. In response to divergent stimuli, macrophages rapidly alter their functions and manifest a wide polarization spectrum with two extremes: M1 or classical activation and M2 or alternative activation. Extracellular vesicles (EVs) secreted from differentially activated macrophages have been shown to have diverse functions, which are primarily attributed to their microRNA cargos. The role of protein cargos in these EVs remains largely unexplored. Therefore, in this study, we focused on the protein cargos in macrophage-derived EVs. Results Naïve murine bone marrow-derived macrophages were treated with lipopolysaccharide or interlukin-4 to induce M1 or M2 macrophages, respectively. The proteins of EVs and their parental macrophages were subjected to quantitative proteomics analyses, followed by bioinformatic analyses. The enriched proteins of M1-EVs were involved in proinflammatory pathways and those of M2-EVs were associated with immunomodulation and tissue remodeling. The signature proteins of EVs shared a limited subset of the proteins of their respective progenitor macrophages, but they covered many of the typical pathways and functions of their parental cells, suggesting their respective M1-like and M2-like phenotypes and functions. Experimental examination validated that protein cargos in M1- or M2-EVs induced M1 or M2 polarization, respectively. More importantly, proteins in M1-EVs promoted viability, proliferation, and activation of T lymphocytes, whereas proteins in M2-EVs potently protected the tight junction structure and barrier integrity of epithelial cells from disruption. Intravenous administration of M2-EVs in colitis mice led to their accumulation in the colon, alleviation of colonic inflammation, promotion of M2 macrophage polarization, and improvement of gut barrier functions. Protein cargos in M2-EVs played a key role in their protective function in colitis. Conclusion This study has yielded a comprehensive unbiased dataset of protein cargos in macrophage-derived EVs, provided a systemic view of their potential functions, and highlighted the important engagement of protein cargos in the pathophysiological functions of these EVs

Tuning of the elastic modulus of a soft polythiophene through molecular doping

Molecular doping of a polythiophene with oligoethylene glycol side chains is found to strongly modulate not only the electrical but also the mechanical properties of the polymer. An oxidation level of up to 18% results in an electrical conductivity of more than 52 S cm(-1) and at the same time significantly enhances the elastic modulus from 8 to more than 200 MPa and toughness from 0.5 to 5.1 MJ m(-3). These changes arise because molecular doping strongly influences the glass transition temperature T-g and the degree of pi-stacking of the polymer, as indicated by both X-ray diffraction and molecular dynamics simulations. Surprisingly, a comparison of doped materials containing mono- or dianions reveals that - for a comparable oxidation level - the presence of multivalent counterions has little effect on the stiffness. Evidently, molecular doping is a powerful tool that can be used for the design of mechanically robust conducting materials, which may find use within the field of flexible and stretchable electronics