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Assessing effectiveness of a person-centered group ANC-PNC model among first-time young mothers and their partners for improving quality and use of MNCH-FP services
Get PDFThis baseline report is part of an operations research project “Healthy Women, Healthy Families (HWHF): Shustha Ma, Shustha Poribar” led by Management Sciences for Health (MSH) in partnership with BRAC, SCOPE, and the Population Council. The project aims to improve quality and increase utilization of maternal, newborn, and child health (MNCH) and family planning (FP) services and information for young mothers-to-be, first-time mothers (FTMs) aged 15-24, and their partners in the urban municipality of Tongi, Gazipur District, Bangladesh, through a group antenatal care ANC-PNC approach. The objectives of this study are to establish baseline values of selected HWHF project result indicators against which the impacts of the project’s intervention can be measured. The target group is young, first-time parents and the study examines the current status of knowledge on MNCH-FP and access to services among FTMs. This quasi-experimental pre-post control group design study employs both quantitative and qualitative data-collection methods. A simple random sampling procedure was employed to select respondents from BRAC FTM lists, while qualitative informants were selected purposively
The Beyond Bias Project: Building evidence to inform practice for provider behavior change programming
No full textBreakthrough RESEARCH, with input from the United States Agency for International Development (USAID) and cross-sectoral implementing partners, developed research and learning agendas (RLAs) to strengthen two important areas of social and behavior change (SBC) programming: integrated SBC programming and provider behavior change (PBC). In this Research Spotlight From Breakthrough RESEARCH, we share key highlights from a PBC project, Beyond Bias, to: 1) Demonstrate how priority RLA questions are being answered to improve PBC programming; 2) Share tools and resources for other program implementation and research partners; and 3) Raise the visibility of current PBC technical work
Drug repurposing for HIV-1 protease inhibitors: High throughput virtual screening, rigid molecular docking and molecular dynamics studies
Get PDFmTORC1/rpS6 and p-FAK-Y407 signaling regulate spermatogenesis: Insights from studies of the adjudin pharmaceutical/toxicant model
No full textIn rodents and humans, the major cellular events at spermatogenesis include self-renewal of spermatogonial stem cells and undifferentiated spermatogonia via mitosis, commitment of spermatogonia to differentiation and transformation to spermatocytes, meiosis, spermiogenesis, and the release of spermatozoa at spermiation. While details of the morphological changes during these cellular events have been delineated, knowledge gap exists between the morphological changes in the seminiferous epithelium and the underlying molecular mechanism(s) that regulate these cellular events. Even though many of the regulatory proteins and biomolecules that modulate spermatogenesis are known based on studies using genetic models, the underlying regulatory mechanism(s), in particular signaling pathways/proteins, remain unexplored since much of the information regarding the signaling regulation is unknown. Studies in the past decade, however, have unequivocally demonstrated that the testis is using several signaling proteins and/or pathways to regulate multiple cellular events to modulate spermatogenesis. These include mTORC1/rpS6/Akt1/2 and p-FAK-Y407. While selective inhibitors and/or agonists and antagonists are available to examine some of these signaling proteins, their use have limitations due to their specificities and also potential systemic cytotoxicity. On the other hand, the use of genetic models has had profound implications for our understanding of the molecular regulation of spermatogenesis, and these knockout (null) models have also revealed the factors that are critical for spermatogenesis. Nonetheless, additional studies using in vitro and in vivo models are necessary to unravel the signaling pathways involved in regulating seminiferous epithelial cycle. Emerging data from studies, such as the use of the adjudin pharmaceutical/toxicant model, have illustrated that this non-hormonal male contraceptive drug is utilizing specific signaling pathways/proteins to induce specific defects in spermatogenesis, yielding mechanistic insights on the regulation of spermatogenesis. We sought to review these recent data in this article, highlighting an interesting approach that can be considered for future studies
Devolved health system capacity in the provision of care for sick newborns and young infants in four counties serving vulnerable populations in Kenya
No full textPossible severe bacterial infections (PSBI) is one of the three leading causes of newborn and young infant mortality globally that can be prevented by timely diagnosis and treatment using suitable antibiotics. High impact interventions such as use of out-patient injectable gentamicin and dispersible Amoxicillin with community-based follow up have been shown to reduce mortality in clinical trials. The objective of this study was to assess the health systems’ preparedness and organizational gaps that may impact execution in providing care for newborns and sick young infants. This formative research study was embedded within a three-year implementation research project in 4 Counties in Kenya. The indicators were based on facility audits for existing capacity to care for newborns and young infants as well as County organizational capacity assessment. The organizational capacity assessment domains were derived from the World Health Organization’s Health Systems Building blocks for health service delivery. The scores were computed by adding average scores in each domain and calculated against the total possible scores to generate a percentage outcome. Statistical analyses were descriptive with adjustment for clustering of data. Overall, the Counties have inadequate organizational capacity for management of sick young infants with Organizational Capacity Index scores of between 61–64%. Among the domains, the highest score was in Health Management Information System and service delivery. The lowest scores were in monitoring and evaluation (M&E). Counties scored relatively low scores in human resources for health and health products and commodities with one scoring poorly for both areas while the rest scored average performance. The four counties revealed varying levels of organizational capacity deficit to effectively manage sick young infants. The key underlying issues for the below par performance include poor coordination, low funding, inadequate supportive supervision, and M&E to enable data utilisation for quality improvement. It was evident that newborn and young infant health services suffer from inadequate infrastructure, equipment, staffing, and coordination. As Kenya, continuously rolls out the guidelines on management of sick young infants, there is need to focus attention to these challenges to enhance sustainable adoption and reduction of young infant morbidity and mortality
Frameworks to envision equitable urban futures in a changing climate: A multi-level, multidisciplinary case study of New York City
No full textCities are at the forefront of climate change action and planning for futures that are concomitantly more resilient and equitable, making local goals imperative for global sustainability. Under the multiple challenges of changing climatic, ecological and socio-economic conditions, cities need the means to meet these goals. We know cities are and will continue to be points of concentrated and diverse populations, socioeconomic vulnerability, amplified exposure, transformed ecosystems and are responsible for the bulk of the world’s greenhouse gas emissions. Yet, much is also unknown and intrinsically uncertain about urban futures: there is a range of potential plausible futures which have differing implications for both potential mitigation and adaptation actions. To better assess these plausible futures, the “global change” research community developed a framework including scenarios that are applicable for global and regional policy, entitled the Shared Socio-economic Pathways (SSPs) and scenarios exploring future emissions that will drive climate change, entitled Representative Concentration Pathways (RCPs). Importantly, this global scale framework does not include specific city-level perspectives or data at the spatial scales necessary to address questions of local relevance. While the SSPs address many of the key population and socioeconomic drivers of climate change, they do not address important concerns that are particularly relevant to cities, such as racial justice, ecosystem change or migration. Nevertheless, city-level impacts will evolve, in part, as a function of the global scale change characterized by the SSPs, and in part based on demographic and social processes already underway. As such, applying a modification of this framework to cities has the potential to help limit local climate impacts, and create a more resilient, equitable city. To address these needs and respond to city and regional stakeholders, we propose a framework for science-based narratives and quantitative projections for cities and metropolitan areas, such as Greater New York City. In this paper, we review a wide-range of existing approaches to generate estimates of future populations and identify their vulnerabilities to climate-change hazards, ranging from subnational population projections or the spatially-explicit allocation of populations linked to SSPs for the US and selected cities, city-specific population forecasting without climate considerations, and participatory approaches to future scenario development and fine-scale, within-city land use change models. By showcasing the strengths and limitations of various approaches and modeling efforts, their spatial and temporal scales, and thematic breadth, we propose a novel framework that leverages state-of-the art quantitative approaches and couples it with stakeholder engagement that can help cities plan equitably under uncertainty
Freeze-drying for the preservation of immunoengineering products
No full textImmunoengineering technologies harness the power of immune system modulators such as monoclonal antibodies, cytokines, and vaccines to treat myriad diseases. Immunoengineering innovations have showed great promise in various practices including oncology, infectious disease, autoimmune diseases, and transplantation. Despite the countless successes, the majority of immunoengineering products contain active moieties that are prone to instability. The current review aims to feature freeze-drying as a robust and scalable solution to the inherent stability challenges in immunoengineering products by preventing the active moiety from degradation. Furthermore, this review describes the stability issues related to immunoengineering products and the utility of the lyophilization process to preserve the integrity and efficacy of immunoengineering tools ranging from biologics to nanoparticle-based vaccines. The concept of the freeze-drying process is described highlighting the quality by design (QbD) for robust process optimization. Case studies of lyophilized immunoengineering technologies and relevant clinical studies using immunoengineering products are discussed
Discovery of novel HIV protease inhibitors using modern computational techniques
No full textThe human immunodeficiency virus type 1 (HIV-1) has continued to be a global concern. With the new HIV incidence, the emergence of multi-drug resistance and the untoward side effects of currently used anti-HIV drugs, there is an urgent need to discover more efficient anti-HIV drugs. Modern computational tools have played vital roles in facilitating the drug discovery process. This research focuses on a pharmacophore-based similarity search to screen 111,566,735 unique compounds in the PubChem database to discover novel HIV-1 protease inhibitors (PIs). We used an in silico approach involving a 3D-similarity search, physicochemical and ADMET evaluations, HIV protease inhibitor prediction (IC50/percent inhibition), rigid receptor–molecular docking studies, binding free energy calculations and molecular dynamics (MD) simulations. The 10 FDA-approved HIV PIs (saquinavir, lopinavir, ritonavir, amprenavir, fosamprenavir, atazanavir, nelfinavir, darunavir, tipranavir and indinavir) were used as reference. The in silico analysis revealed that fourteen out of the twenty-eight selected optimized hit molecules were within the acceptable range of all the parameters investigated. The hit molecules demonstrated significant binding affinity to the HIV protease (PR) when compared to the reference drugs. The important amino acid residues involved inhydrogen bonding and ï-ï stacked interactions include ASP25, GLY27, ASP29, ASP30 and ILE50. These interactions help to stabilize the optimized hit molecules in the active binding site of the HIV-1 PR (PDB ID: 2Q5K). HPS/002 and HPS/004 have been found to be most promising in terms of IC50/percent inhibition (90.15%) of HIV-1 PR, in addition to their drug metabolism and safety profile. These hit candidates should be investigated further as possible HIV-1 PIs with improved efficacy and low toxicity through in vitro experiments and clinical trial investigations
ShangRing versus Mogen clamp for early infant male circumcision in eastern sub-Saharan Africa: A multicentre, non-inferiority, adaptive, randomised controlled trial
No full textBackground: Use of medical devices represents a unique opportunity to facilitate scale-up of early infant male circumcision (EIMC) across sub-Saharan Africa. The ShangRing, a circumcision device prequalified by WHO, is approved for use in adults and adolescents and requires topical anaesthesia only. We aimed to investigate the safety and efficacy of the ShangRing versus the Mogen clamp for EIMC in infants across eastern sub-Saharan Africa. Methods: In this multicentre, non-inferiority, open-label, randomised controlled trial, we enrolled healthy male infants (aged Findings: Between Sept 17, 2018, and Dec 20, 2019, a total of 1420 infants were assessed for eligibility, of whom 1378 (97·0%) were enrolled. 689 (50·0%) infants were randomly assigned to undergo EIMC by ShangRing and 689 (50·0%) by Mogen clamp. 43 (6·2%) adverse events were observed in the ShangRing group and 61 (8·9%) in the Mogen clamp group (p=0·078). The most common treatment-related AE was intraoperative pain (Neonatal Infant Pain Scale score ≥5), with 19 (2·8%) events in the ShangRing and 23 (3·3%) in the Mogel clamp group. Rates of moderate and severe AEs were similar between both groups (29 [4·2%] in the ShangRing group vs 30 [4·4%] in the Mogen clamp group; difference –0·1%; one-sided 95% CI upper limit of 1·7%; p=0·89). No treatment-related deaths were reported. Interpretation: Use of the ShangRing device for EIMC showed safety, achieved high caregiver satisfaction, and did not differ from the Mogen clamp in other key measures. The ShangRing could be used by health systems and international organisations to further scale up EIMC across sub-Saharan Africa