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Irradiation of the small intestine can result in depletion of the epithelial stem cell compartment and is often the dose-limiting factor for radiotherapeutic treatment of tumors in the abdominal and pelvic region. Since mitotic cells are most sensitive to radiation, significant radioprotection can be achieved by reducing the number of cells in mitosis at the time of irradiation. We have previously shown that administration of macrophage inflammatory protein (MIP) -1alpha induces a transient 50% reduction in the number of mitotic cells in small intestinal crypts, including the stem cell region, and therefore, MIP-1alpha pretreatment before radiation exposure could result in a substantial reduction of the side effects associated with radiotherapy. Groups of adult mice were exposed to different doses of radiation (6, 8, 10, or 12 Gy), with or without prior administration of 200 microg BB-10010/kg 3 hr before irradiation and radiation damage was assessed by means of the microcolony survival assay. MIP-1alpha pretreatment resulted in significantly increased numbers of surviving crypts (10%) when compared to untreated irradiated animals. The observed radioprotective effects of MIP-1alpha in the small intestine should translate into reduced side effects in a clinically relevant radiotherapy context and could allow larger doses of radiation to be delivered to patients with tumors in the abdominal or pelvic region. [ABSTRACT FROM AUTHOR]

BB10010/MIP-1 alpha reduces the number of proliferating cells in the small intestine, strongly suggesting a radioprotective potential in this organ. This study was designed to optimize BB10010 administration for maximal radioprotection. In single administration protocols 1 or 4 mg/kg of BB10010 was injected into mice 2, 4 or 10 hr before death. In double administration protocols an initial dose of either 0.4 or 200 microg/kg, and a second dose (2.5 hr apart) of 200 microg/kg 4 hr before death were administered. The number of vincristine-arrested metaphases were counted on individually microdissected crypts from the midpoint of the small intestine. When compared to the smaller doses of BB 10010 used in our previous studies, the higher doses used in these experiments did not result in any further reduction in the number of proliferating cells under any of the protocols assessed. Furthermore, some values were found to be above not only those observed with the smaller doses, but also above untreated controls. It is concluded that a single dose of 200 microg/kg of BB10010 offers the most consistent reduction of mitotic cells, and is, therefore, considered optimal for assessment of radioprotection. [ABSTRACT FROM AUTHOR]

Purpose: Irradiation of the small intestine in the mouse induces damaging structural alterations to the architecture of the enteric mucosa. There is growing interest in the possible relevance of underlying additional pathology when appreciating the total response of tissues to irradiation. The possibility that small intestinal mucosal abnormalities in the streptozotocin-induced diabetic mouse may exacerbate radiation-induced injury was tested by examining the combined effects of the two treatments. Materials and methods: Streptozotocin-diabetic and -non-diabetic mice were exposed to 10 Gy abdominal X-radiation. Profiles of mucosal epithelial cell populations were quantified and comparisons with corresponding groups of unirradiated mice made on the third day post-irradiation. Results: The histological appearances of the small intestinal mucosa were similar in both groups of irradiated mice, but the numbers of profiles of crypts and of columnar, goblet, Paneth and entero-endocrine cells were depressed in these groups when compared with values in corresponding groups of unirradiated mice. However, the expression of radiation damage in the diabetic mouse was less severe than in the non-diabetic mouse, particularly in the jejunum where the changes attendant on the onset of diabetes were most marked. Conclusion: These findings suggest that the response of mouse to radiation may be moderated by the presence of this type of pathophysiology. However, there is no evidence that the damage produced by streptozotocin-induced diabetes and radiation is additive. [ABSTRACT FROM AUTHOR]

Background: The small-intestinal epithelium, a rapidly proliferating tissue, is highly sensitive to cycle-specific agents such as radiation. Macrophage inflammatory protein (MIP)-1 alpha has been shown to reduce cell proliferation in bone marrow, seminiferous epithelium, and skin. The current work investigates the activity of an MIP-1 alpha variant, BB-10010, in the gut. Methods: A single dose of either 0.4 μg/kg or 200 μg/kg was administered to mice 2, 4, 6, 8, 10, 12, or 14 h before animal death. Fifteen crypts from the midpoint of the small intestine were dissected from each animal and squashed, and the numbers of vincristine-arrested metaphases was counted for each fifth of the crypts. Results: A 40%-50% reduction of accumulated metaphases throughout all crypt segments was observed in animals injected with 200 μg/kg of BB-10010 2 h and 4 h before death (P < 0.0001). The animals that received 0.4 μg/kg showed a similar effect at 4 h (P < 0.0001). Conclusions: The results provide evidence of a significant reduction in numbers of intestinal cryptal cells passing through mitosis at specific time periods after a single administration of BB-10010. By putting these cells temporarily out of the mitotic phase of the cell cycle this protein might reduce the side effects of radiation therapy to patients undergoing abdominal or pelvic treatments. [ABSTRACT FROM AUTHOR]

Abstract Background The government of Kenya is making plans to implement a social health insurance program by transforming the National Hospital Insurance Fund (NHIF) into a universal health coverage program. This paper examines the determinants associated with participation in the NHIF among residents of urban slums in Nairobi city. Methods The study used data from the Nairobi Urban Health and Demographic Surveillance System in two slums in Nairobi city, where a total of about 60,000 individuals living in approximately 23,000 households are under surveillance. Descriptive statistics and multivariate logistic regression analysis were used to describe the characteristics of the sample and to identify factors associated with participation in the NHIF program. Results Only 10% of the respondents were participating in the NHIF program, while less than 1% (0.8%) had private insurance coverage. The majority of the respondents (89%) did not have any type of insurance coverage. Females were more likely to participate in the NHIF program (OR = 2.4; p < 0.001), while respondents who were formerly in a union (OR = 0.5; p < 0.05) and who were never in a union (OR = 0.6; p < 0.05) were less likely to have public insurance coverage. Respondents working in the formal employment sector (OR = 4.1; p < 0.001) were more likely to be enrolled in the NHIF program compared to those in the informal sector. Membership in microfinance institutions such as savings and credit cooperative organizations (SACCOs) and community-based savings and credit groups were important determinants of access to health insurance. Conclusions The proportion of slum residents without any type of insurance is high, which underscores the need for a social health insurance program to ensure equitable access to health care among the poor and vulnerable segments of the population. As the Kenyan government moves toward transforming the NHIF into a universal health program, it is important to harness the unique opportunities offered by both the formal and informal microfinance institutions in improving health care capacity by considering them as viable financing options within a comprehensive national health financing policy framework.

Abstract Background Recent trends in global vaccination coverage have shown increases with most countries reaching 90% DTP3 coverage in 2008, although pockets of undervaccination continue to persist in parts of sub-Saharan Africa particularly in the urban slums. The objectives of this study were to determine the vaccination status of children aged between 12-23 months living in two slums of Nairobi and to identify the risk factors associated with incomplete vaccination. Methods The study was carried out as part of a longitudinal Maternal and Child Health study undertaken in Korogocho and Viwandani slums of Nairobi. These slums host the Nairobi Urban Health and Demographic Surveillance System (NUHDSS) run by the African Population and Health Research Centre (APHRC). All women from the NUHDSS area who gave birth since September 2006 were enrolled in the project and administered a questionnaire which asked about the vaccination history of their children. For the purpose of this study, we used data from 1848 children aged 12-23 months who were expected to have received all the WHO-recommended vaccinations. The vaccination details were collected during the first visit about four months after birth with follow-up visits repeated thereafter at four month intervals. Full vaccination was defined as receiving all the basic childhood vaccinations by the end of 24 months of life, whereas up-to-date (UTD) vaccination referred to receipt of BCG, OPV 1-3, DTP 1-3, and measles vaccinations within the first 12 months of life. All vaccination data were obtained from vaccination cards which were sighted during the household visit as well as by recall from mothers. Multivariate models were used to identify the risk factors associated with incomplete vaccination. Results Measles coverage was substantially lower than that for the other vaccines when determined using only vaccination cards or in addition to maternal recall. Up-to-date (UTD) coverage with all vaccinations at 12 months was 41.3% and 51.8% with and without the birth dose of OPV, respectively. Full vaccination coverage (57.5%) was higher than up-to-date coverage (51.8%) at 12 months overall, and in both slum settlements, using data from cards. Multivariate analysis showed that household assets and expenditure, ethnicity, place of delivery, mother's level of education, age and parity were all predictors of full vaccination among children living in the slums. Conclusions The findings show the extent to which children resident in slums are underserved with vaccination and indicate that service delivery of immunization services in the urban slums needs to be reassessed to ensure that all children are reached.

Introduction Assessing clinical judgement objectively and economically presents a challenge in academic medicine. The authors developed a situational judgement test (SJT) to measure fourth-year medical students' clinical judgement. Methods A knowledge-based, single-best-answer SJT was developed by a panel of subject matter experts (SMEs). The SJT included 30 scenarios, each with five response options ranked ordinally from most to least appropriate. A computer-based format was used, and the SJT was piloted by two cohorts of fourth-year medical students at California University of Science and Medicine in 2022 and 2023 upon completion of an internship preparation course. Subsequently, students completed an optional survey. Evaluated scoring methods included original ordinal ranking, dichotomous, dichotomous with negative correction, distance from SME best answer, and distance from SME best answer squared. Results The SJT was completed by 142 fourth-year medical students. Cronbach's alpha ranged from 0.39 to 0.85, depending on the scoring method used. The distance-from-SME-best-answer-squared method yielded the highest internal consistency, which was considered acceptable. Using this scoring method, the mean score was 72.89 (SD = 48.32, range = 26-417), and the standard error of measurement was 18.41. Item analysis found that seven (23%) scenarios were of average difficulty, 13 (43%) had a good or satisfactory discrimination index, and nine (30%) had a distractor efficiency of at least 66%. Most students preferred the SJT to a traditional multiple-choice exam (16; 62%) and felt it was an appropriate tool to assess clinical judgement (15; 58%). Conclusions The authors developed and piloted an SJT to assess clinical judgement among medical students. Although not achieving validation, subsequent development of the SJT will focus on expanding the SME concordance panel, improving difficulty and discrimination indices, and conducting parallel forms reliability and adverse impact analyses., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. California University of Science and Medicine issued approval HS-2022-06. Please be advised that the Institutional Review Board (IRB) of CUSM received your application on 3/10/2022 regarding the project entitled above. The IRB proposal was evaluated through expedited review by designated IRB members. Based on their comments, the IRB Office determined that this research proposal is under Exempt Category 2, and the exemption has been approved. Please note that this decision does not exclude the requirements of other CUSM administrative departments or offices if certain situations are related. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Rei et al.)

Horizontal and vertical integration within medical school curricula, truncated contact hours available to teach basic biomedical sciences, and diverse assessment methods have left histology educators searching for an answer to a fundamental question-what ensures competency for medical students in histology upon completion of medical school? The Liaison Committee for Medical Education (LCME) and the Commission on Osteopathic College Accreditation (COCA) advocate faculty to provide medical students with a list of learning objectives prior to any educational activities, regardless of pedagogy. It is encouraged that the learning objectives are constructed using higher-order and measurable action verbs to ensure student-centered learning and assessment. A survey of the literature indicates that there is paucity of knowledge about competencies, goals, and learning objectives appropriate for histology education in preclinical years. To address this challenge, an interactive online taskforce, comprising faculty from across the United States, was assembled. The outcome of this project was a desired set of competencies for medical students in histology with educational goals and learning objectives to achieve them., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© International Association of Medical Science Educators 2019.)

Background: Every curriculum needs to be reviewed, implemented and evaluated; it must also comply with the regulatory standards. This report demonstrates the value of curriculum mapping (CM), which shows the spatial relationships of a curriculum, in developing and managing an integrated medical curriculum., Methods: A new medical school developed a clinical presentation driven integrated curriculum that incorporates the active-learning pedagogical practices of many educational institutions worldwide while adhering to the mandated requirements of the accreditation bodies. A centralized CM process was run in parallel as the curriculum was being developed. A searchable database, created after the CM data was uploaded into an electronic curriculum management system, was used to ensure placing, integrating, evaluating and revising the curricular content appropriately., Results: CM facilitated in a) appraising the content integration, b) identifying gaps and redundancies, c) linking learning outcomes across all educational levels (i.e. session to course to program), c) organizing the teaching schedules, instruction methods, and assessment tools and d) documenting compliance with accreditation standards., Conclusions: CM is an essential tool to develop, review, improve and refine any integrated curriculum however complex. Our experience, with appropriate modifications, should help other medical schools efficiently manage their curricula and fulfill the accreditation requirements at the same time.

Aims: Polymyxin E was used for treating gram-negative bacterial infections but not recently for fear of its nephrotoxicity. Silybin has potential to counteract nephrotoxicity; however, few studies have investigated its protective effect on the kidney in an animal model. The purpose of the present study was to assess whether silybin could decrease elevated urine and serum renal biochemical markers induced by polymyxin E in rat kidney., Methods: Forty rats were divided randomly into four groups of 10 rats: control (I), vehicle (II), treatment (III, using polymyxin E), and protection (IV, using silybin and polymyxin E). Urine was collected daily for 7 days to test for N-acetyl-beta-D-glucosaminidase (NAG). Serum was collected after euthanizing the rats on day 7 to test kidney functions. RESULTS Group III had significant increases in NAG (all P < 0.001) compared with the other groups, but no differences were found between the other groups. Significant differences in kidney functions were found between Group III and Groups I and II, and between Group IV and Groups I and II (all P < 0.001). No differences were found between Groups III and IV., Conclusions: Group III results suggested an affection of the renal glomeruli and tubules, and Group IV results suggested a possible protective effect of silybin against polymyxin E-induced nephrotoxicity. Additional studies are recommended that use different doses of silybin for Groups III and IV to test for statistical differences for kidney functions and that test the protective effect of silybin against nephrotoxicity induced by polymyxin E in humans., (© 2017 Wiley Periodicals, Inc.)

Objective: To simulate sacrospinous ligament fixation on cadaveric specimens, describe the surrounding retroperitoneal anatomy, and estimate the risk to nerves and arteries for the purposes of optimizing safe suture placement., Methods: Sacrospinous ligament fixation was performed on eight fresh-tissue female cadavers using a Capio ligature capture device. Distances from placed sutures to the following structures were measured: ischial spine; fourth sacral root; pudendal nerve; the nerve to coccygeus muscle; the nerve to levator ani muscle; inferior gluteal artery; and internal pudendal artery. Periligamentous anatomy was examined in an additional 17 embalmed cadaver dissections., Results: Sacrospinous ligament length was not seen to differ significantly between sides. The fourth sacral spinal nerve was seen most commonly associated with the medial third of the ligament, whereas the pudendal nerve and the nerves to coccygeus and levator ani muscles were associated with the lateral third. The inferior gluteal artery was seen leaving the greater sciatic foramen a median 15.8 mm (range 1.8-48.0, CI 14.9-22.3) above the ligament, whereas the internal pudendal artery exited just above the ischial spine. The two sets of sutures were placed 20.5 mm (range 9.2-34.4, CI 19.7-24.7) and 24.8 mm (range 12.4-46.2, CI 24.0-30.0) medial to the ischial spine, respectively. No structures were directly damaged by placed sutures. The nerves to coccygeus and levator ani were closest and arteries farthest from the placed sutures., Conclusion: The middle segment of the sacrospinous ligament has the lowest incidence of nerves and arteries associated with it. This study confirms that the nerves supplying the pelvic floor muscles are at a higher risk from entrapment than the pudendal nerve.

Significant changes have been implemented in the way undergraduate medical education is structured. One of the challenges for component courses such as histology in medical and dental curricula is to restructure and deliver training within new frameworks. This article describes the process of aligning the purpose and experience in histology laboratory to the goal of applying knowledge gained to team-based medical practice at Tulane University School of Medicine. Between 2011 and 2015, 711 medical students took either a traditional laboratory-based histology course (353 students) or a team-based hybrid histology course with active learning in laboratory (358 students). The key difference was in the laboratory component of the hybrid course - interactive table conferences in histology-during which students developed new competencies by working in teams, reviewing images, solving problems by applying histology concepts, and sharing learning. Content, faculty and online resources for microscopy were the same in both courses. More student-student and student-faculty interactions were evident during the hybrid course but student evaluation ratings and grades showed reductions following introduction of table conferences when compared to previous ratings. However, outcomes at National Board of Medical Examiners(®) (NBME(®) ) Subject Examination in Histology and Cell Biology showed significant improvement (72.4 ± 9.04 and 76.44 ± 9.36 for percent correct answers, traditional and hybrid courses, respectively, P < 0.0001). This model of table conferences to augment the traditional histology laboratory experience exemplifies the extent that restructuring enhancements can be used in currently taught courses in the undergraduate medical curriculum. Anat Sci Educ 9: 286-294. © 2016 American Association of Anatomists., (© 2016 American Association of Anatomists.)

Background: Enhancing accountability in health systems is increasingly emphasised as crucial for improving the nature and quality of health service delivery worldwide and particularly in developing countries. Accountability mechanisms include, among others, health facilities committees, suggestion boxes, facility and patient charters. However, there is a dearth of information regarding the nature of and factors that influence the performance of accountability mechanisms, especially in developing countries. We examine community members' experiences of one such accountability mechanism, the health facility charter in Kericho District, Kenya., Methods: A household survey was conducted in 2011 among 1,024 respondents (36% male, 64% female) aged 17 years and above stratified by health facility catchment area, situated in a division in Kericho District. In addition, sixteen focus group discussions were conducted with health facility users in the four health facility catchment areas. Quantitative data were analysed through frequency distributions and cross-tabulations. Qualitative data were transcribed and analysed using a thematic approach., Results: The majority (65%) of household survey respondents had seen their local facility service charter, 84% of whom had read the information on the charter. Of these, 83% found the charter to be useful or very useful. According to the respondents, the charters provided useful information about the services offered and their costs, gave users a voice to curb potential overcharging and helped users plan their medical expenses before receiving the service. However, community members cited several challenges with using the charters: non-adherence to charter provisions by health workers; illegibility and language issues; lack of expenditure records; lack of time to read and understand them, often due to pressures around queuing; and socio-cultural limitations., Conclusion: Findings from this study suggest that improving the compliance of health facilities in districts across Kenya with regard to the implementation of the facility service charter is critical for accountability and community satisfaction with service delivery. To improve the compliance of health facilities, attention needs to be focused on mechanisms that help enforce official guidelines, address capacity gaps, and enhance public awareness of the charters and their use.

Background: In Kenya, where 60 to 80% of the urban residents live in informal settlements (frequently referred to as slums), out-of-pocket (OOP) payments account for more than a third of national health expenditures. However, little is known on the extent to which these OOP payments are associated with personal or household financial catastrophe in the slums. This paper seeks to examine the incidence and determinants of catastrophic health expenditure among urban slum communities in Kenya., Methods: We use a unique dataset on informal settlement residents in Kenya and various approaches that relate households OOP payments for healthcare to total expenditures adjusted for subsistence, or income. We classified households whose OOP was in excess of a predefined threshold as facing catastrophic health expenditures (CHE), and identified the determinants of CHE using multivariate logistic regression analysis., Results: The results indicate that the proportion of households facing CHE varies widely between 1.52% and 28.38% depending on the method and the threshold used. A core set of variables were found to be key determinants of CHE. The number of working adults in a household and membership in a social safety net appear to reduce the risk of catastrophic expenditure. Conversely, seeking care in a public or private hospital increases the risk of CHE., Conclusion: This study suggests that a substantial proportion of residents of informal settlements in Kenya face CHE and would likely forgo health care they need but cannot afford. Mechanisms that pool risk and cost (insurance) are needed to protect slum residents from CHE and improve equity in health care access and payment.

Background: The World Health Organization recommends Bacillus Calmette-Guérin (BCG) vaccination against tuberculosis be given at birth. However, in many developing countries, pre-term and low birth weight infants get vaccinated only after they gain the desired weight. In Kenya, the ministry of health recommends pre-term and low birth weight infants to be immunized at the time of discharge from hospital irrespective of their weight. This paper seeks to understand the effects of birth weight on timing of BCG vaccine., Methods: The study was conducted in two Nairobi urban informal settlements, Korogocho and Viwandani which hosts the Nairobi Urban Health and Demographic Surveillance system. All infants born in the study area since September 2006 were included in the study. Data on immunization history and birth weight of the infant were recorded from child's clinic card. Follow up visits were done every four months to update immunization status of the child. A total of 3,602 infants were included in this analysis. Log normal accelerated failure time parametric model was used to assess the association between low birth weight infants and time to BCG immunization., Results: In total, 229 (6.4%) infants were low birth weight. About 16.6% of the low birth weight infants weighed less than 2000 grams and 83.4% weighed between 2000 and 2490 grams. Results showed that, 60% of the low birth weight infants received BCG vaccine after more than five weeks of life. Private health facilities were less likely to administer a BCG vaccine on time compared to public health facilities. The effects of low birth weight on females was 0.60 and 0.97-times that of males for infants weighing 2000-2499 grams and for infants weighing <2000 grams respectively. The effect of low birth weight among infants born in public health facilities was 1.52 and 3.94-times that of infants delivered in private health facilities for infants weighing 2000-2499 grams and those weighing < 2000 grams respectively., Conclusion: Low birth weight infants received BCG immunization late compared to normal birth weight infants. Low birth weight infants delivered in public health facilities were more likely to be immunized much later compared to private health facilities.

Introduction: Rapid urbanisation in Kenya has resulted in growth of slums in urban centres, characterised by poverty, inadequate social services and poor health outcomes. The government's initiatives to improve access to quality healthcare for mothers and children are largely limited to public health facilities, which are few and/or inaccessible in underserved areas such as the slums. The 'Partnership for Maternal, Newborn and Child Health' (PAMANECH) project is being implemented in two Nairobi slums, Viwandani and Korogocho, to assess the impact of strengthening public-private partnerships for the delivery of healthcare on the health of mothers, newborns and young children in two informal settlements in Kenya., Methods and Analysis: This is a quasi-experimental study; our approach is to support private as well as public health providers and the community to enhance access to and demand for quality healthcare services. Key activities include: infrastructural upgrade of selected Private Not-For-Profit health facilities operating in the two slums, building capacity for healthcare providers as well as the Health Management Teams in Nairobi, facilitating provision of supportive supervision by the local health authorities and forming networks of Community Health Volunteers (CHVs) to create demand for health services. To assess the impact of the intervention, the study is utilising multiple data sources using a combination of qualitative and quantitative methods. A baseline survey was conducted in 2013 and an end-line survey will be conducted at least 1 year after full implementation of the intervention. Systematic monitoring and documentation of the intervention is on-going to strengthen the case for causal inference., Ethics and Dissemination: Ethical approval for the study was obtained from the Kenya Medical Research Institute. Key messages from the results will be packaged and widely disseminated through workshops, conference presentations, reports, factsheets and academic publications to facilitate uptake by policymakers., Protocol Registration Number: KEMRI- NON-SSC-PROTOCOL No. 393., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)