eIF1A/eIF5B Interaction Network and its Functions in Translation Initiation Complex Assembly and Remodeling

Eukaryotic translation initiation is a highly regulated process involving multiple steps, from 43S pre-initiation complex (PIC) assembly, to ribosomal subunit joining. Subunit joining is controlled by the G-protein eukaryotic translation initiation factor 5B (eIF5B). Another protein, eIF1A, is involved in virtually all steps, including subunit joining. The intrinsically disordered eIF1A C-terminal tail (eIF1A-CTT) binds to eIF5B Domain-4 (eIF5B-D4). The ribosomal complex undergoes conformational rearrangements at every step of translation initiation; however, the underlying molecular mechanisms are poorly understood. Here we report three novel interactions involving eIF5B and eIF1A: (i) a second binding interface between eIF5B and eIF1A; (ii) a dynamic intramolecular interaction in eIF1A between the folded domain and eIF1A-CTT; and (iii) an intramolecular interaction between eIF5B-D3 and -D4. The intramolecular interactions within eIF1A and eIF5B interfere with one or both eIF5B/eIF1A contact interfaces, but are disrupted on the ribosome at different stages of translation initiation. Therefore, our results indicate that the interactions between eIF1A and eIF5B are being continuously rearranged during translation initiation. We present a model how the dynamic eIF1A/eIF5B interaction network can promote remodeling of the translation initiation complexes, and the roles in the process played by intrinsically disordered protein segments

Coping Strategies and Help-Seeking Behaviors among Survivors of Intimate Partner Violence: A Qualitative Study of Spouses of Men with Heavy Drinking in India

Background. Despite the high prevalence of intimate partner violence (IPV) against women in India (33%), there are persistently low rates of disclosure and help-seeking amongst survivors. The aim of this study was to explore both coping strategies employed by survivors and the perceived barriers and facilitators to seeking support from informal and formal resource networks. Methods. We conducted semistructured, in-depth qualitative interviews with thirty-five women survivors of IPV in Goa, India, in secure, private locations, utilizing flipcharts and vignettes to elicit deeper insights into efficacies of support resources. The data were transcribed, translated, and analyzed utilizing qualitative content analysis. Results. The most common coping mechanisms cited by survivors involved passive resistance, such as self-distraction, keeping quiet during violent outbursts, and leaving the home temporarily. Generally, survivors sought support from informal support networks (the natal family, in-laws, neighbors/community members, and close friends) before approaching formal support structures (medical/legal professionals, professors, police, and nongovernment organizations). In fact, informal structures were often facilitators of formal help-seeking. Survivors sought help at various stages of their marital relationship. Primary deterrents to help-seeking included the normalization of IPV by survivors and providers alike, resulting in the stigmatization of disclosing experiences of IPV and ostracism of survivors and close relatives; another barrier was a general lack of awareness of existing support resources. Conclusion. Our findings reveal that there are numerous barriers to help-seeking and shortcomings of support resources. Survivors’ evaluations of support resources reveal that robust, community-level, and meso-level structural changes are required to promote help-seeking behaviors, including the destigmatization of IPV amongst providers and broader society and raising awareness of available support resources

Alcohol use among adolescents in India: a systematic review

Abstract Background Alcohol use is typically established during adolescence and initiation of use at a young age poses risks for short- and long-term health and social outcomes. However, there is limited understanding of the onset, progression and impact of alcohol use among adolescents in India. The aim of this review is to synthesise the evidence about prevalence, patterns and correlates of alcohol use and alcohol use disorders in adolescents from India. Methods Systematic review was conducted using relevant online databases, grey literature and unpublished data/outcomes from subject experts. Inclusion and exclusion criteria were developed and applied to screening rounds. Titles and abstracts were screened by two independent reviewers for eligibility, and then full texts were assessed for inclusion. Narrative synthesis of the eligible studies was conducted. Results Fifty-five peer-reviewed papers and one report were eligible for inclusion in this review. Prevalence of ever or lifetime alcohol consumption ranged from 3.9% to 69.8%; and prevalence of alcohol consumption at least once in the past year ranged from 10.6% to 32.9%. The mean age for initiation of drinking ranged from 14.4 to 18.3 years. Some correlates associated with alcohol consumption included being male, older age, academic difficulties, parental use of alcohol or tobacco, non-contact sexual abuse and perpetuation of violence. Conclusion The evidence base for alcohol use among adolescents in India needs a deeper exploration. Despite gaps in the evidence base, this synthesis provides a reasonable understanding of alcohol use among adolescents in India and can provide direction to policymakers. </jats:sec

Examining the need & potential for biomedical engineering to strengthen health care delivery for displaced populations & victims of conflict

Abstract Conflict and the subsequent displacement of populations creates unique challenges in the delivery of quality health care to the affected population. Equitable access to quality care demands a multi-pronged strategy with a growing need, and role, for technological innovation to address these challenges. While there have been significant contributions towards alleviating the burden of conflict via data informatics and analytics, communication technology, and geographic information systems, little has been done within biomedical engineering. This article elaborates on the causes for gaps in biomedical innovation for refugee populations affected by conflict, tackles preconceived notions, takes stock of recent developments in promising technologies to address these challenges, and identifies tangible action items to create a stronger and sustainable pipeline for biomedical technological innovation to improve the health and well-being of an increasing group of vulnerable people around the world

Intermittent fasting improves hepatic end points in nonalcoholic fatty liver disease: A systematic review and meta-analysis

Background and Aims:. Despite NAFLD being the most prevalent liver disease globally, currently there are no FDA-approved treatments, and weight loss through caloric restriction and enhanced physical activity is the recommended treatment strategy. Intermittent fasting (IF) has been proposed as an alternative strategy with additional cardiometabolic benefits. In this systematic review and meta-analysis, we evaluated the anthropometric, biochemical, and hepatic impacts of IF in patients with NAFLD. Methods:. MEDLINE, EMBASE, Cochrane Central, and conference abstracts were searched for IF interventions in adults with NAFLD until April 2, 2023. Meta-analysis with a random effects model was used to compare pre-intervention and post-intervention changes in anthropometric, biochemical, and hepatic end points in the IF intervention group with the control group. Publication bias was assessed using Egger’s test. Results:. Fourteen studies were included in the systematic review and ten in the meta-analysis (n = 840 participants, 44.64% male). Studies varied in modalities for NAFLD diagnosis, duration of IF (4–52 weeks), and type of IF (5:2 diet, modern alternate-day fasting, time-restricted eating, or religious fasting). Body weight, body mass index, and waist to hip ratio all significantly improved following fasting intervention (p< 0.05). Adults with NAFLD showed an improvement in serum alanine transaminase, aspartate aminotransferase, hepatic steatosis (controlled attenuation parameter measured by vibration-controlled transient elastography), and hepatic stiffness (measured by vibration-controlled transient elastography) after fasting intervention (p < 0.05). Conclusions:. There is limited, but moderate- to high-quality evidence to suggest that IF can improve hepatic end points and promote weight loss in adults with NAFLD. Larger randomized controlled studies with extended duration are needed to further validate our findings

Adolescent Health Series: The status of adolescent mental health research, practice and policy in sub-Saharan Africa: A narrative review.

Sub-Saharan Africa (SSA) has the fastest growing adolescent population in the world. In addition to developmental changes, adolescents in SSA face health and socioeconomic challenges that increase their vulnerability to mental ill-health. This paper is a narrative review of adolescent mental health (AMH) in SSA with a focus on past achievements, current developments, and future directions in the areas of research, practice and policy in the region. We describe the status of AMH in the region, critical factors that negatively impact AMH, and the ways in which research, practice and policy have responded to this need. Depression, anxiety and post-traumatic stress disorders are the most common mental health problems among adolescents in SSA. Intervention development has largely been focused on HIV/AIDS service delivery in school or community programs by non-specialist health workers. There is a severe shortage of specialised AMH services, poor integration of services into primary health care, lack of a coordinated inter-sectoral collaboration, and the absence of clear referral pathways. Policies for the promotion of AMH have been given less attention by policymakers, due to stigma attached to mental health problems, and an insufficient understanding of the link between mental health and social determinants, such as poverty. Given these gaps, traditional healers are the most accessible care available to help-seeking adolescents. Sustained AMH research with a focus on the socioeconomic benefits of implementing evidence-based, contextually adapted psychosocial interventions might prove useful in advocating for much needed policies to improve AMH in SSA

eIF1A/eIF5B interaction network and its functions in translation initiation complex assembly and remodeling

Eukaryotic translation initiation is a highly regulated process involving multiple steps, from 43S pre-initiation complex (PIC) assembly, to ribosomal subunit joining. Subunit joining is controlled by the G-protein eukaryotic translation initiation factor 5B (eIF5B). Another protein, eIF1A, is involved in virtually all steps, including subunit joining. The intrinsically disordered eIF1A C-terminal tail (eIF1A-CTT) binds to eIF5B Domain-4 (eIF5B-D4). The ribosomal complex undergoes conformational rearrangements at every step of translation initiation; however, the underlying molecular mechanisms are poorly understood. Here we report three novel interactions involving eIF5B and eIF1A: (i) a second binding interface between eIF5B and eIF1A; (ii) a dynamic intramolecular interaction in eIF1A between the folded domain and eIF1A-CTT; and (iii) an intramolecular interaction between eIF5B-D3 and -D4. The intramolecular interactions within eIF1A and eIF5B interfere with one or both eIF5B/eIF1A contact interfaces, but are disrupted on the ribosome at different stages of translation initiation. Therefore, our results indicate that the interactions between eIF1A and eIF5B are being continuously rearranged during translation initiation. We present a model how the dynamic eIF1A/eIF5B interaction network can promote remodeling of the translation initiation complexes, and the roles in the process played by intrinsically disordered protein segments

Modeling patient access to therapeutic oxytocin in Zanzibar, Tanzania

Abstract Background Our objective is to estimate the effects of therapeutic oxytocin supply chain factors and social determinants of health on patient access to oxytocin in low-income settings using system dynamics modeling. Postpartum hemorrhage (PPH), a major cause of maternal mortality disproportionately affects women in low and middle income countries (LMICs). The World Health Organization recommends therapeutic oxytocin as the frontline uterotonic for PPH management and prevention. However, lack of access to quality therapeutic oxytocin in Tanzania, and throughout Sub-Saharan Africa, continues to result in a high number of preventable maternal deaths. Methods We used publicly available data from Zanzibar and Sub-Saharan Africa, literature review, oxytocin degradation kinetics and previously developed systems dynamics models to understand the barriers in patient access to quality therapeutic oxytocin. Results The model makes four basic predictions. First, there is a major gap between therapeutic oxytocin procurement and availability. Second, it predicts that at current population increase rates, oxytocin supply will have to be doubled in the next 30 years. Third, supply and storage temperature until 30 °C has minimal effect on oxytocin quality and finally distance of 5 km or less to birthing facility has a small effect on overall access to oxytocin. Conclusions The model provides a systems level approach to therapeutic oxytocin access, incorporating supply and procurement, socio-economic factors, as well as storage conditions to understand how women’s access to oxytocin over time can be sustained for better health outcomes

Integrating assisted tele-psychiatry into primary healthcare in Goa, India: a feasibility study

BACKGROUND: Tele-psychiatry is an increasingly acceptable and feasible platform to deliver mental health care with the potential to increase access to care in low-resource settings. We aim to examine the acceptability and preliminary impact of the delivery of assisted tele-psychiatry services in primary healthcare settings in Goa, India. METHODS: Before-after uncontrolled treatment cohort study. In total, 161 adults with either a mental or alcohol use disorder were provided tele-consultation by psychiatrists through a customised video conferencing platform, along with medication or counselling (via trained lay counsellors) or both as needed. Data on socio-demographics, clinical outcomes and process indicators were collected at baseline and 3 months post-baseline. Paired t tests were used to assess clinical outcomes pre- and post-treatment using the General Health Questionnaire-12 (GHQ-12) and World Health Organisation Disability Adjustment Schedule (WHODAS) 2.0, and logistic regression was used to find associations between changes in these scores and various factors. RESULTS: The most common diagnosis was depression (35%). Post-treatment, there was a significant reduction in both GHQ-12 and WHODAS 2.0 scores. Participants showed high satisfaction with the tele-psychiatry services and technology platform. Improvement in GHQ-12 score was associated with being employed [OR 8.74 (1.92–39.75, p = 0.005)] and being a homemaker [OR 6.42 (CI 1.61–25.57, p = 0.008)]. CONCLUSION: Treatment of mental disorders through a tele-psychiatry platform appears to be highly acceptable and is associated with improved clinical outcomes. Considering its potential for scalability, a model of assisted tele-psychiatry integrated into primary care can be an important strategy to increase access to mental healthcare in low-resource settings