Community-based financing of family planning in developing countries: A systematic review

In this systematic review, we gather evidence on community financing schemes and insurance programs for family planning in developing countries, and we assess the impact of these programs on primary outcomes related to contraceptive use. To identify and evaluate the research findings, we adopt a four‐stage review process that employs a weight‐of‐evidence and risk‐of‐bias analytic approach. Out of 19,138 references that were identified, only four studies were included in our final analysis, and only one study was determined to be of high quality. In the four studies, the evidence on the impact of community‐based financing on family planning and fertility outcomes is inconclusive. These limited and mixed findings suggest that either: 1) more high‐quality evidence on community‐based financing for family planning is needed before any conclusions can be made; or 2) community‐based financing for family planning may, in fact, have little or no effect on family planning outcomes.Funding from the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored program executed by the World Health Organization, is gratefully acknowledged. The authors thank members of the WHO technical working group on financing family planning for their valuable comments. In addition, the authors thank Iqbal Shah for his support throughout the review process and for his technical guidance on this manuscript. (UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP); World Health Organization)Published versio

Changing medical student attitudes to patient safety: A multicentre study

Background: Although patient safety is becoming widely taught in medical schools, its effect has been less rigorously evaluated. We describe a multicentre study to evaluate student changes in patient safety attitudes using a standardized instrument, the Attitudes to Patient Safety Questionnaire3 (APSQ3). Methods: A patient safety training package designed for medical students was delivered in the first year and second year in four Australian medical schools. It comprises eight face-to-face modules, each of two hours. Seminars start with an interactive introduction using questions, video and role play, followed by small group break-outs to discuss a relevant case study. Groups are led by medical school tutors with no prior training in patient safety. Students and tutors then reassemble to give feedback and reinforce key concepts. Knowledge and attitudes to patient safety were measured using the APSQ3, delivered prior to safety teaching, at the end of the first and second years and 12 months after teaching ceased. Results: A significant improvement in attitude over time was demonstrated for four of nine key items measured by the APSQ3: value of patient safety teaching; danger of long working hours, value of team work and the contribution patients can make in reducing error. Informal feedback from students was very positive. Conclusion: We showed persistent, positive learning from a patient safety education intervention 12 months after teaching finished. Building on the introduction of patient safety teaching into medical schools, pathways for motivated students such as appropriate electives, option terms and team-based research projects would be of value

Prototype Biology-Based Radiation Risk Module Project

Biological effects of space radiation and risk mitigation are strategic knowledge gaps for the Evolvable Mars Campaign. The current epidemiology-based NASA Space Cancer Risk (NSCR) model contains large uncertainties (HAT #6.5a) due to lack of information on the radiobiology of galactic cosmic rays (GCR) and lack of human data. The use of experimental models that most accurately replicate the response of human tissues is critical for precision in risk projections. Our proposed study will compare DNA damage, histological, and cell kinetic parameters after irradiation in normal 2D human cells versus 3D tissue models, and it will use a multi-scale computational model (CHASTE) to investigate various biological processes that may contribute to carcinogenesis, including radiation-induced cellular signaling pathways. This cross-disciplinary work, with biological validation of an evolvable mathematical computational model, will help reduce uncertainties within NSCR and aid risk mitigation for radiation-induced carcinogenesis

University students’ experiences of the teaching and learning of an acupuncture programme : a South African case study

The quality of teaching and learning in educational programmes at higher education institutions (HEIs) cannot be overemphasised. This is of particular importance in skills programmes, such as acupuncture, because the teaching and learning of acupuncture at HEIs significantly influence students' competence in the world of work. Acupuncture is one of the most popular alternative treatments globally and contributes to improving public health. To provide quality acupuncture services to the public, HEIs must ensure that their students are competent in implementing the knowledge and skills gained in the programmes. The focus of this study is to explore students' experiences with the teaching and learning of the acupuncture programme at a South African HEI. A conceptual framework adapted from Shulman's (1986) Pedagogical Content Knowledge model and Mishra and Koehler's (2006) Technological Pedagogical and Content Knowledge model was utilised as a theoretical lens in this study. A descriptive qualitative single case study design was employed. The authors adopted a purposive sampling technique to recruit ten participants from the identified HEI. The findings of this study revealed that students' ambivalent experiences in the acupuncture programme. The findings will contribute to the improvement of quality teaching and learning of an acupuncture programme. This study concluded that diverse teaching and learning strategies should be implemented in the acupuncture programme, especially during the COVID-19 pandemic.https://www.ijlter.org/index.php/ijlterhj2023Early Childhood Educatio

Interactions of the SAP Domain of Human Ku70 with DNA Substrate: A Molecular Dynamics Study

NASA is developing a systems biology approach to improve the assessment of health risks associated with space radiation. The primary toxic and mutagenic lesion following radiation exposure is the DNA double strand break (DSB), thus a model incorporating proteins and pathways important in response and repair of this lesion is critical. One key protein heterodimer for systems models of radiation effects is the Ku70/80 complex. The Ku70/80 complex is important in the initial binding of DSB ends following DNA damage, and is a component of nonhomologous end joining repair, the primary pathway for DSB repair in mammalian cells. The SAP domain of Ku70 (residues 556-609), contains an a helix-extended strand-helix motif and similar motifs have been found in other nucleic acid-binding proteins critical for DNA repair. However, the exact mechanism of damage recognition and substrate specificity for the Ku heterodimer remains unclear in part due to the absence of a high-resolution structure of the SAP/DNA complex. We performed a series of molecular dynamics (MD) simulations on a system with the SAP domain of Ku70 and a 10 base pairs DNA duplex. Large-scale conformational changes were observed and some putative binding modes were suggested based on energetic analysis. These modes are consistent with previous experimental investigations. In addition, the results indicate that cooperation of SAP with other domains of Ku70/80 is necessary to explain the high affinity of binding as observed in experiments

A novel approach to sequence validating protein expression clones with automated decision making

<p>Abstract</p> <p>Background</p> <p>Whereas the molecular assembly of protein expression clones is readily automated and routinely accomplished in high throughput, sequence verification of these clones is still largely performed manually, an arduous and time consuming process. The ultimate goal of validation is to determine if a given plasmid clone matches its reference sequence sufficiently to be "acceptable" for use in protein expression experiments. Given the accelerating increase in availability of tens of thousands of unverified clones, there is a strong demand for rapid, efficient and accurate software that automates clone validation.</p> <p>Results</p> <p>We have developed an Automated Clone Evaluation (ACE) system – the first comprehensive, multi-platform, web-based plasmid sequence verification software package. ACE automates the clone verification process by defining each clone sequence as a list of multidimensional discrepancy objects, each describing a difference between the clone and its expected sequence including the resulting polypeptide consequences. To evaluate clones automatically, this list can be compared against user acceptance criteria that specify the allowable number of discrepancies of each type. This strategy allows users to re-evaluate the same set of clones against different acceptance criteria as needed for use in other experiments. ACE manages the entire sequence validation process including contig management, identifying and annotating discrepancies, determining if discrepancies correspond to polymorphisms and clone finishing. Designed to manage thousands of clones simultaneously, ACE maintains a relational database to store information about clones at various completion stages, project processing parameters and acceptance criteria. In a direct comparison, the automated analysis by ACE took less time and was more accurate than a manual analysis of a 93 gene clone set.</p> <p>Conclusion</p> <p>ACE was designed to facilitate high throughput clone sequence verification projects. The software has been used successfully to evaluate more than 55,000 clones at the Harvard Institute of Proteomics. The software dramatically reduced the amount of time and labor required to evaluate clone sequences and decreased the number of missed sequence discrepancies, which commonly occur during manual evaluation. In addition, ACE helped to reduce the number of sequencing reads needed to achieve adequate coverage for making decisions on clones.</p

SIV antigen immunization induces transient antigen-specific T cell responses and selectively activates viral replication in draining lymph nodes in retroviral suppressed rhesus macaques

<p>Abstract</p> <p>Background</p> <p>HIV infection causes a qualitative and quantitative loss of CD4⁺T cell immunity. The institution of anti-retroviral therapy (ART) restores CD4⁺T cell responses to many pathogens, but HIV-specific responses remain deficient. Similarly, therapeutic immunization with HIV antigens of chronically infected, ART treated subjects results in poor induction of HIV-specific CD4 responses. In this study, we used a macaque model of ART treatment during chronic infection to study the virologic consequences of SIV antigen stimulation in lymph nodes early after immunization. Rhesus CMV (RhCMV) seropositive, Mamu A*01 positive rhesus macaques were chronically infected with SIVmac251 and treated with ART. The immune and viral responses to SIV gag and RhCMV pp65 antigen immunization in draining lymph nodes and peripheral blood were analyzed. Animals were immunized on contralateral sides with SIV gag and RhCMV pp65 encoding plasmids, which allowed lymph nodes draining each antigen to be obtained at the same time from the same animal for direct comparison.</p> <p>Results</p> <p>We observed that both SIV and RhCMV immunizations stimulated transient antigen-specific T cell responses in draining lymph nodes. The RhCMV-specific responses were potent and sustained (50 days post-immunization) in the periphery, while the SIV-specific responses were transient and extinguished quickly. The SIV antigen stimulation selectively induced transient SIV replication in draining lymph nodes.</p> <p>Conclusions</p> <p>The data are consistent with a model whereby viral replication in response to SIV antigen stimulation limits the generation of SIV antigen-specific responses and suggests a potential mechanism for the early loss and poor HIV-specific CD4⁺T cell response observed in HIV-infected individuals.</p

Evidence Report: Risk of Acute Radiation Syndromes Due to Solar Particle Events

Crew health and performance may be impacted by a major solar particle event (SPE), multiple SPEs, or the cumulative effect of galactic cosmic rays (GCR) and SPEs. Beyond low-Earth orbit, the protection of the Earth's magnetosphere is no longer available, such that increased shielding and protective mechanisms are necessary in order to prevent acute radiation sickness and impacts to mission success or crew survival. While operational monitoring and shielding are expected to minimize radiation exposures, there are EVA scenarios outside of low-Earth orbit where the risk of prodromal effects, including nausea, vomiting, anorexia, and fatigue, as well as skin injury and depletion of the blood-forming organs (BFO), may occur. There is a reasonable concern that a compromised immune system due to high skin doses from a SPE or due to synergistic space flight factors (e.g., microgravity) may lead to increased risk to the BFO. The primary data available at present are derived from analyses of medical patients and persons accidentally exposed to acute, high doses of low-linear energy transfer (LET) (or terrestrial) radiation. Data more specific to the space flight environment must be compiled to quantify the magnitude of increase of this risk and to develop appropriate protection strategies. In particular, information addressing the distinct differences between solar proton exposures and terrestrial exposure scenarios, including radiation quality, dose-rate effects, and non-uniform dose distributions, is required for accurate risk estimation

Insertion of heterometals into the NifEN-associated iron–molybdenum cofactor precursor

The cofactors of Mo-, V-, Fe-dependent nitrogenases are believed to be highly homologous in structure despite the different types of heterometals (Mo, V, and Fe) they contain. Previously, a precursor form of the FeMo cofactor (FeMoco) was captured on NifEN, a scaffold protein for FeMoco biosynthesis. This all-Fe precursor closely resembles the Fe/S core structure of the FeMoco and, therefore, could reasonably serve as a precursor for all nitrogenase cofactors. Here, we report the heterologous incorporation of V and Fe into the NifEN-associated FeMoco precursor. EPR and activity analyses indicate that V and Fe can be inserted at much reduced efficiencies compared with Mo, and incorporation of both V and Fe is enhanced in the presence of homocitrate. Further, native polyacrylamide gel electrophoresis experiments suggest that NifEN undergoes a significant conformational rearrangement upon metal insertion, which allows the subsequent NifEN–MoFe protein interactions and the transfer of the cofactor between the two proteins. The combined outcome of these in vitro studies leads to the proposal of a selective mechanism that is utilized in vivo to maintain the specificity of heterometals in nitrogenase cofactors, which is likely accomplished through the redox regulation of metal mobilization by different Fe proteins (encoded by nifH, vnfH, and anfH, respectively), as well as the differential interactions between these Fe proteins and their respective scaffold proteins (NifEN and VnfEN) in the Mo-, V-, and Fe-dependent nitrogenase systems

Rho-kinase Regulates Energy Balance by Targeting Hypothalamic Leptin Receptor Signaling

Leptin regulates energy balance. However, knowledge of the critical intracellular transducers of leptin signaling remains incomplete. Here we report that Rho-kinase 1 (ROCK1) regulates leptin action on body weight homeostasis by activating JAK2, an initial trigger of leptin receptor signaling. Leptin promotes the physical interaction of JAK2 and ROCK1, thereby increasing phosphorylation of JAK2 and downstream activation of Stat3 and FOXO1. Mice lacking ROCK1 in either POMC or AgRP neurons, mediators of leptin action, display obesity and impaired leptin sensitivity. In addition, deletion of ROCK1 in the arcuate nucleus markedly enhances food intake, resulting in severe obesity. Of note, ROCK1 is a specific mediator of leptin, but not insulin, regulation of POMC neuronal activity. Our data identify ROCK1 as a key regulator of leptin action on energy homeostasis