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Objective: To assess the effect of a free healthcare policy for children under five years old implemented in Burkina Faso since April 2016, on the use of health care of non‐malarial febrile illnesses (NMFI). Methods: To assess the immediate and long‐term effect of the free healthcare policy in place, we conducted an interrupted time series analysis of routinely collected data on febrile illnesses from three urban primary health centres of Ouagadougou between 1 January 2015 and 31 December 2016. Results: Of the 39 046 febrile cases reported in the study period, 17 017 NMFI were included in the study. Compared to the period before the intervention, we observed an immediate, non‐statistically significant increase of 7% in the number of NMFI (IRR = 1.07; 95% CI = 0.75, 1.51). Compared to the trend that would have been expected in absence of the intervention, the results showed a small but sustained increase of 6% in the trend of monthly number of NMFI during the intervention period (IRR = 1.06; 95%CI = 1.01, 1.12). Conclusion: Our study highlighted an increase in the uptake of healthcare services, specifically for NMFI by children under five years of age, after the implementation of a free care policy. This analysis contributes to informing decision makers on the need to strengthen the capacities of healthcare centres and to anticipate the challenges of the sustainability of this policy. [ABSTRACT FROM AUTHOR]

A herpes simplex virus (HSV)-specific long-term T-cell clone has been established from the draining lymph node cells of BALB/c mice; the cells required repeated in vitro restimulation with UV-irradiated virus. The established T-cell clone expresses the Thy-1 and Lyt-1+2,3- surface antigens. For optimal proliferation of the cloned cells, both the presence of specific antigen and an exogenous source of T-cell growth factor are required. The proliferative response of the cloned T cells was found to be virus-specific but it did not distinguish between HSV-1 and HSV-2. Adoptive cell transfer of the cloned T cells helped primed B cells to produce anti-herpes antibodies: the response was antigen-specific and cell dose-dependent. The clone failed to produce a significant DTH reaction in vivo, but did produce high levels of macrophage-activating factor. Furthermore, the T-cell clone could protect from HSV infection, as measured by a reduction in local virus growth, and by enhanced survival following the challenge of mice with a lethal dose of virus. The mechanism(s) whereby this clone protects in vivo is discussed. [ABSTRACT FROM AUTHOR]

This paper reports on the characteristics of killing by a human and a murine tuberculin (PPD)-specihc T helper clone of targets to which PPD was attached via the Iectin concanavalin A (Con A). The killing was specific for PPD from M. tuberculosis; and targets coupled to Con A alone or to PPD from M. paratuberculosis were not killed. Target cells carrying Con A-PPD were more effectively lysed than PPD-pulsed cells. This form of lymphocyte killing, though highly significant, was inefficient. Maximum killing of PPD carrying targets was 31-40% at effector to target ratios of 20:1 and at 16 h. Cells carrying 2 x 106 molecules of PPD and less than 1.5x106 molecules Con A per cell were killed most efficiently. A major distinction between this helper T cell killing and that mediated by cytotoxic T cells was that both TH clones displayed bystander lysis and killed PPD uncoupled targets when these were cultured with syngeneic PPD-bound targets. This suggests that the mechanism of cytotoxicity may involve soluble mediators. [ABSTRACT FROM AUTHOR]

Peripheral blood mononuclear cells (PBMC) of normal individuals were found lo contain a proportion (4-9% )of in vivo activated lymphoid cells (IVALC). These IVALC were characterized by their expression of interleukin 2 (IL-2) receptors, and by the ability to proliferate in the presence of exogenous IL-2. There was a good correlation between the proportion of IVALC in different cell populations and the level of cell proliferation to IL-2. It was found that IVALC isolated from autologous PBMC of Bacillus Calmette-Guerin (BCG)-immunized individuals contained no significant proportion of purified protein derivative (PPD)-reactive lymphocytes. The addition of IVALC markedly enhanced proliferative responses of the autologous T4+T8- IL-2 receptor-negative cell cultures to antigen stimulation. An increased proportion of activated (IL-2 receptor-positive) lymphocytes was generated in PBMC as compared to autologous T4+T8- IL-2 receptor negative cell cultures alter stimulation with PPD. Limiting dilution analysis showed that IL-2 responsive IVALC through expansion markedly affected the cloning efficiency of antigen-proliferating I cells of autologous PPD-stimulated PBMC cultures. Only 1 out of every 11-25 blast cells generated in the PBMC cultures could establish itself as a growing colony based on determinations in six BCG-positive individuals. By using a T4+T8- population depleted of IVALC to generate PPD-reactive lymphocytes a three- to four-fold increase in the cloning efficiency of antigen-specific cells was obtained [ABSTRACT FROM AUTHOR]

Murine thymocytes and peripheral lymphocytes bind autologous erythrocytes via H-2L-regionrestricted receptors. After inhibiting autorosetting with different erythrocyte sonicates the specificity of these anti-self receptors was examined in F1 hybrid and chimaeric mice. Most F1 lymphocytes simultaneously expressed receptors against both parental haplotypes. Furthermore, analysis of lymphocytes from allogeneic and semi-allogeneic chimaeras clearly demonstrated that radioresistant elements in the recipient thymus did not modify the haplotype specificity of the receptors on donor-derived lymphocytes. [ABSTRACT FROM AUTHOR]

Rosetting between thymocytes and autologous erythrocytes is mediated by receptors on thymocytes that primarily recognize self H-2L molecules on erythrocytes. This paper describes preliminary attempts to chemically characterize the receptor and acceptor molecules involved in this H-2-restricted interaction. On the basis of sugar inhibition studies and the sensitivity of the receptors and acceptors to protease and glycosidase treatments it appears that a protein receptor on thymocytes recognizes the carbohydrate portion of a glycoprotein on erythrocytes. Furthermore, the thymocyte receptor appears to recognize terminal D-galactose, D-mannose and sialic acid residues on a branched-chain carbohydrate structure on erythrocytes, with mouse strains of different H-2 haplotype expressing carbohydrate structures that differ in the linkage of these three terminal sugars. These findings indicate that H-2-restricted carbohydrate-protein interactions can occur between cells, a conclusion with important theoretical implications. [ABSTRACT FROM AUTHOR]

Background. Inducible costimulator (ICOS) is rapidly upregulated with T-cell stimulation and may represent an escape pathway for T-cell costimulation in the setting of CD40/CD154 costimulation blockade. Induction treatment exhibited no efficacy in a primate renal allograft model, but rodent transplant models suggest that the addition of delayed ICOS/ICOS-L blockade may prolong allograft survival and prevent chronic rejection. Here, we ask whether ICOS-Ig treatment, timed to anticipate ICOS upregulation, prolongs NHP cardiac allograft survival or attenuates pathogenic alloimmunity. Methods. Cynomolgus monkey heterotopic cardiac allograft recipients were treated with αCD40 (2C10R4, d0-90) either alone or with the addition of delayed ICOS-Ig (d63-110). Results. Median allograft survival was similar between ICOS-Ig + αCD40 (120 days, 120-125 days) and αCD40 (124 days, 89-178 days) treated animals, and delayed ICOS-Ig treatment did not prevent allograft rejection in animals with complete CD40 receptor coverage. Although CD4+ TEM cells were decreased in peripheral blood (115 ± 24) and mLNs (49 ± 1.9%) during ICOS-Ig treatment compared with monotherapy (214 ± 27%, P = 0.01; 72 ± 9.9%, P = 0.01, respectively), acute and chronic rejection scores and kinetics of alloAb elaboration were similar between groups. Conclusions. Delayed ICOS-Ig treatment with the reagent tested is probably ineffective in modulating pathogenic primate alloimmunity in this model.

The shape of the head is considered the most important criterion in determining the standard breeds of dogs. It is of much significance to study the skull typology of the Ghanaian local dog in order to establish a template of its identification as a breed and to generate data which could be useful in the comparative anatomy of the skulls of dogs. A total of twenty skulls of adult dogs of two age groups were used in this study. 31 parameters were measured and 6 skull indices were calculated on their basis. The group of skulls from older fully grown dogs showed higher values in all parameters. Results of the current study will provide baseline reference data on skull parameters of local dolichocephalic dogs. More importantly, results obtained could be useful in veterinary applied anatomy and clinical practice in areas including forensic medicine, plastic or cosmetic maxillofacial surgery, neurosurgery of the cranium, acupuncture, nerve block and other clinical manipulations involving the head. [ABSTRACT FROM AUTHOR]

Abstract Background Burkina Faso's immunization program has benefited regularly from national and international support. However, national immunization coverage has been irregular, decreasing from 34.7% in 1993 to 29.3% in 1998, and then increasing to 43.9% in 2003. Undoubtedly, a variety of factors contributed to this pattern. This study aims to identify both individual and systemic factors associated with complete vaccination in 1998 and 2003 and relate them to variations in national and international policies and strategies on vaccination of rural Burkinabé children aged 12-23 months. Methods Data from the 1998 and 2003 Demographic and Health Surveys and the Ministry of Health's 1997 and 2002 Statistical Yearbooks, as well as individual interviews with central and regional decision-makers and with field workers in Burkina's healthcare system, were used to carry out a multilevel study that included 805 children in 1998 and 1,360 children in 2003, aged 12-23 months, spread over 44 and 48 rural health districts respectively. Results In rural areas, complete vaccination coverage went from 25.9% in 1998 to 41.2% in 2003. District resources had no significant effect on coverage and the impact of education declined over time. The factors that continued to have the greatest impact on coverage rates were poverty, with its various dimensions, and the utilization of other healthcare services. However, these factors do not explain the persistent differences in complete vaccination between districts. In 2003, despite a trend toward district homogenization, differences between health districts still accounted for a 7.4% variance in complete vaccination. Conclusion Complete vaccination coverage of children is improving in a context of worsening poverty. Education no longer represents an advantage in relation to vaccination. Continuity from prenatal care to institutional delivery creates a loyalty to healthcare services and is the most significant and stable explanatory factor associated with complete vaccination of children. Healthcare service utilization is the result of a dynamic process of interaction between communities and the healthcare system; understanding this process is the key to understanding better the factors underlying the complete vaccination of children.

Background: Burkina Faso's immunization program has benefited regularly from national and international support. However, national immunization coverage has been irregular, decreasing from 34.7% in 1993 to 29.3% in 1998, and then increasing to 43.9% in 2003. Undoubtedly, a variety of factors contributed to this pattern. This study aims to identify both individual and systemic factors associated with complete vaccination in 1998 and 2003 and relate them to variations in national and international policies and strategies on vaccination of rural Burkinabé children aged 12-23 months.Methods: Data from the 1998 and 2003 Demographic and Health Surveys and the Ministry of Health's 1997 and 2002 Statistical Yearbooks, as well as individual interviews with central and regional decision-makers and with field workers in Burkina's healthcare system, were used to carry out a multilevel study that included 805 children in 1998 and 1,360 children in 2003, aged 12-23 months, spread over 44 and 48 rural health districts respectively.Results: In rural areas, complete vaccination coverage went from 25.9% in 1998 to 41.2% in 2003. District resources had no significant effect on coverage and the impact of education declined over time. The factors that continued to have the greatest impact on coverage rates were poverty, with its various dimensions, and the utilization of other healthcare services. However, these factors do not explain the persistent differences in complete vaccination between districts. In 2003, despite a trend toward district homogenization, differences between health districts still accounted for a 7.4% variance in complete vaccination.Conclusion: Complete vaccination coverage of children is improving in a context of worsening poverty. Education no longer represents an advantage in relation to vaccination. Continuity from prenatal care to institutional delivery creates a loyalty to healthcare services and is the most significant and stable explanatory factor associated with complete vaccination of children. Healthcare service utilization is the result of a dynamic process of interaction between communities and the healthcare system; understanding this process is the key to understanding better the factors underlying the complete vaccination of children. [ABSTRACT FROM AUTHOR]

Background: Healthcare-associated infections (HCAI) are common in long-term care facilities (LTCF) and cause significant burden. Infection prevention and control (IPC) measures include the clinical best practices (CBP) of hand hygiene, hygiene and sanitation, screening, and basic and additional precautions. Few studies demonstrate their cost-effectiveness in LTCF, and those that do, largely focus on one CBP. An overarching synthesis of IPC economic analyses in this context is warranted. The aim of this paper is to conduct a systematic review of economic evaluations of CBP applied in LTCF., Methods: We twice queried CINAHL, Cochrane, EconLit, Embase, Medline, Web of Science and Scopus for studies published in the last three decades of economic evaluations of CBP in LTCF. We included controlled and randomized clinical trials, cohort, longitudinal, follow-up, prospective, retrospective, cross-sectional, and simulations studies, as well as those based on mathematical or statistical modelling. Two reviewers conducted study selection, data extraction, and quality assessment of studies. We applied discounting rates of 3%, 5% and 8%, and presented all costs in 2022 Canadian dollars. The protocol of this review was registered with Research Registry (reviewregistry1210) and published in BMC Systematic Reviews., Findings: We found 3,331 records and then 822 records; ten studies were retained. The economic analyses described were cost-minimization (n = 1), cost-benefit (n = 1), cost-savings (n = 2), cost-utility (n = 2) and cost-effectiveness which included cost-utility and cost-benefit analyses (n = 4). Four studies were high quality, three were moderate, and three were low quality. Inter-rater agreement for quality assessment was 91⋅7%. All studies (n = 10) demonstrated that CBP associated with IPC are clinically effective in LTCF and many (n = 6) demonstrated their cost effectiveness., Interpretation: Ongoing economic evaluation research of IPC remains essential to underpin healthcare policy choices guided by empirical evidence for LTCF residents and staff., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

We present provocative data that in addition to the expected progressive age-related involution, mammary gland aging can occur in a cyclical pattern and is dictated by maternal ancestry. In cyclical aging, mammary glands of 11 and 19 months old mice share genetic and proteomic signatures, which are enriched in breast cancer-related pathways, but are absent at 3 and 14 months. Since incidence of breast cancer shows a bimodal age distribution at 45 (~11m in mice) and 65 (~ 19m in mice), cyclical aging may contribute to these peaks of cancer susceptibility. Conversely, since the mammary glands at 3 and 14 months cluster together hierarchically, the cancer-associated peaks seem separated by a rejuvenation phase. Since cyclical aging is observed in mice with extended lifespan, these findings raise the possibility that if oncogenic mutations are avoided during the pro-oncogenic phases, through its rejuvenation phase, cyclical aging may impact multiple organs leading to extended longevity., Competing Interests: Competing interests The authors declare no competing interests.

Background: To assess topical dorzolamide as medical therapy for idiopathic full-thickness macular holes (FTMHs)., Methods: Randomised, double-blinded, placebo-controlled, single-centre clinical trial involving 32 patients with idiopathic small FTMHs (<400 μm ). Participants in both arms used topical dorzolamide 2% or saline thrice daily for 8 weeks with monthly OCT. Those with persisting FTMH underwent vitrectomy with ILM peel and gas tamponade. The primary outcome was the rate of FTMH closure at the end of treatment., Results: Between 6 March 2020 and 16 June 2023, 32 eligible patients were enrolled: 16 participants in each arm. All participants in both groups were included in the final analysis. At the final visit, 3 of 16 (18.8%) patients in both the topical dorzolamide and placebo group demonstrated closure. There was no statistically significant difference in the proportion of FTMH closure between the control and treatment group (p = 1.00), nor statistically significant difference in the mean change in best corrected visual acuity (BCVA; p = 0.909). There was no difference in the change in FTMH diameter between groups (p = 0.225). No serious adverse events were reported in either group., Conclusion: Topical dorzolamide was safe but not superior to placebo in the functional and anatomical outcomes of FTMH., (© 2024 The Author(s). Clinical & Experimental Ophthalmology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists.)

Objective: To describe the development of a web-based data collection tool to track the management and outcomes of uveal melanoma patients., Design: Description of a clinical registry., Participants: Patients with uveal melanoma., Methods: A panel of expert ocular oncologists, with input from other relevant specialties and individuals with expertise in registry development, collaborated to formulate a minimum data set to be collected to track patient centred, real-world outcomes in uveal melanoma. This data set was used to create the Fight Tumour Blindness! (FTB!) registry within Save Sight Registries., Results: The data set to be collected includes patient demographics and medical history, baseline visit, follow-up visit including tumour treatment, metastatic staging and surveillance, pathology, and patient-reported questionnaires. The inbuilt mechanisms to ensure efficient and complete data collection are described., Conclusions: The FTB! registry can be used to monitor outcomes for patients with uveal melanoma. It allows benchmarking of outcomes and comparisons between different clinics and countries., (Copyright © 2024 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Cholangiocarcinomas are a highly heterogeneous group of malignancies that, despite recent progress in the understanding of their molecular pathogenesis and clinical management, continue to pose a major challenge to public health. The traditional view posits that cholangiocarcinomas derive from the neoplastic transformation of cholangiocytes lining the biliary tree. However, increasing genetic and experimental evidence has recently pointed to a more complex, and nuanced, scenario for the potential cell of origin of cholangiocarcinomas. Hepatocytes as well as hepatic stem/progenitor cells are being considered as additional potential sources, depending on microenvironmental contexts, including liver injury. The hypothesis of potentially diverse cells of origin for cholangiocarcinoma, albeit controversial, is certainly not surprising given the plasticity of the cells populating the liver as well as the existence of liver cancer subtypes with mixed histologic and molecular features. This review carefully examines the current pathologic, genomic, and experimental evidence supporting the existence of multiple cells of origin of liver and biliary tract cancers, with particular focus on cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma., Competing Interests: Disclosure Statement J.-C.N. received research funding from Bayer and Ipsen. The other authors declare no financial or personal disclosures relevant to the contents of the manuscript. B.G. declares no conflict of interests., (Copyright © 2024. Published by Elsevier Inc.)

Background & Aims: Transforming growth factor β (TGF-β) plays an oncogenic role in advanced cancer by promoting cell proliferation, metastasis and immunosuppression. PMEPA1 (prostate transmembrane protein androgen induced 1) has been shown to promote TGF-β oncogenic effects in other tumour types. Thus, we aimed to explore the role of PMEPA1 in hepatocellular carcinoma (HCC)., Methods: We analysed 1,097 tumours from patients with HCC, including discovery (n = 228) and validation (n = 361) cohorts with genomic and clinicopathological data. PMEPA1 levels were assessed by qPCR (n = 228), gene expression data (n = 869) and at the single-cell level (n = 54). Genetically engineered mouse models overexpressing MYC+PMEPA1 compared to MYC were generated and molecular analyses were performed on the HCCs obtained., Results: PMEPA1 was overexpressed in 18% of HCC samples (fold-change >2; n = 201/1,097), a feature associated with TGF-β signalling activation ( p < 0.05) and absence of gene body hypomethylation ( p < 0.01). HCCs showing both TGF-β signalling and high PMEPA1 levels (12% of cases) were linked to immune exhaustion, late TGF-β activation, aggressiveness and higher recurrence rates after resection, in contrast to HCCs with only TGF-β signalling (8%) or PMEPA1 overexpression (9%). Single-cell RNA sequencing analysis identified PMEPA1 expression in HCC and stromal cells. PMEPA1 -expressing tumoural cells were predicted to interact with CD4 + regulatory T cells and CD4 + CXCL13 + and CD8 + exhausted T cells. In vivo , overexpression of MYC + PMEPA1 led to HCC development in ∼60% of mice and a decreased survival compared to mice overexpressing MYC alone ( p = 0.014). MYC + PMEPA1 tumours were enriched in TGF-β signalling, paralleling our human data., Conclusions: In human HCC, PMEPA1 upregulation is linked to TGF-β activation, immune exhaustion, and an aggressive phenotype. Overexpression of PMEPA1+MYC led to tumoural development in vivo , demonstrating the oncogenic role of PMEPA1 in HCC for the first time., Impact and Implications: PMEPA1 can enhance the tumour-promoting effects of TGF-β in cancer. In this study, we demonstrate that PMEPA1 is highly expressed in ∼18% of patients with hepatocellular carcinoma (HCC), a feature associated with poor prognosis, TGF-β activation and exhaustion of immune cells. Similarly, in mouse models, PMEPA1 overexpression promotes HCC development, which demonstrates its oncogenic role. The identification of PMEPA1 as oncogenic driver in HCC and its role in immune exhaustion and poor clinical outcomes enhances our understanding of HCC pathogenesis and opens new avenues for targeted therapeutic interventions., (© 2024 The Authors.)

Background and Aims: Sustained inflammation and hepatocyte injury in chronic liver disease activate HSCs to transdifferentiate into fibrogenic, contractile myofibroblasts. We investigated the role of protocadherin 7 (PCDH7), a cadherin family member not previously characterized in the liver, whose expression is restricted to HSCs., Approach and Results: We created a PCDH7 fl/fl mouse line, which was crossed to lecithin retinol acyltransferase-Cre mice to generate HSC-specific PCDH7 knockout animals. HSC contraction in vivo was tested in response to the HSC-selective vasoconstrictor endothelin-1 using intravital multiphoton microscopy. To establish a PCDH7 null HSC line, cells were isolated from PCDH7 fl/fl mice and infected with adenovirus-expressing Cre. Hepatic expression of PCDH7 was strictly restricted to HSCs. Knockout of PCDH7 in vivo abrogated HSC-mediated sinusoidal contraction in response to endothelin-1. In cultured HSCs, loss of PCDH7 markedly attenuated contractility within collagen gels and led to altered gene expression in pathways governing adhesion and vasoregulation. Loss of contractility in PCDH7 knockout cells was impaired Rho-GTPase signaling, as demonstrated by altered gene expression, reduced assembly of F-actin fibers, and loss of focal adhesions., Conclusions: The stellate cell-specific cadherin, PCDH7, is a novel regulator of HSC contractility whose loss leads to cytoskeletal remodeling and sinusoidal relaxation., (Copyright © 2024 American Association for the Study of Liver Diseases.)

This study aims to measure the level of entry into motherhood among internally displaced adolescent girls in Kaya and Kongoussi communes, Burkina Faso, and to analyze the factors associated with it. Data were collected from 404 adolescent girls aged 12-19 years in a cross-sectional survey conducted between July and August 2021. The proportion of internally displaced adolescent girls who had started childbearing was 26.5%. Age, marital status and current use of modern contraception were found to be significantly associated with entry into motherhood among internally displaced adolescent girls. Marital status mediates the effect of religion and employment on entry of the adolescents into motherhood. The results suggest that actions aimed at preventing early marriage and improving employment opportunities among adolescent girls could potentially prevent their early entry into motherhood., Competing Interests: The Authors declared no conflict of interest, (African Journal of Reproductive Health © 2024.)

Background: The COVID-19 pandemic wreaked havoc on long-term care facilities (LTCFs). Some LTCFs performed better than others at slowing COVID-19 transmission. Emerging literature has mostly described infection prevention and control strategies implemented by LTCFs during the pandemic. However, there is a need for a comprehensive review of factors that influenced the performance of LTCFs in containing COVID-19 spread to inform public health policy., Objective: To build on the existing literature, we conducted a scoping review of factors that influenced LTCF performance during the COVID-19 pandemic using a multidimensional conceptual framework of performance., Methods: We followed the Joanna Briggs Institute's methodology for scoping reviews. We queried CINAHL, MEDLINE (Ovid), CAIRN, Science Direct, Scopus, and Web of Science for peer-reviewed literature in English or French published between January 1 st , 2020 and December 31 st , 2021. Retrieved records were screened for context (COVID-19 pandemic), population (LTCFs), interest (internal and external factors that influenced LTCF performance), and outcomes (dimensions of performance: equity, accessibility, reactivity, safety, continuity, efficacy, viability, efficiency). Descriptive characteristics of included articles were summarized. Dimensions of performance as well as internal (e.g., facility characteristics) and external (e.g., visitors) factors identified to have influenced LTCF performance were presented., Results: We retained 140 articles of which 68% were classified as research articles, 47% originated in North America, and most covered a period between March and July 2020. The most frequent dimensions of performance were "efficacy" (75.7%) and "safety" (75.7%). The most common internal factors were "organizational context" (72.9%) and "human resources" (62.1%), and the most common external factors were "visitors" (27.1%) and "public health guidelines" (25.7%)., Conclusions: Our review contributes to a global interest in understanding the impact of the COVID-19 pandemic on vulnerable populations residing and working in LTCFs. Though a myriad of factors were reported, a lack of randomized controlled trials makes it impossible to establish causality between the identified factors and LTCF performance. The use of a multidimensional framework can be recommended to evaluate healthcare system performance not merely in terms of efficacy and safety, but alongside other critical dimensions such as efficiency and equity., Trial Registration: Research Registry ID: researchregistry7026., (© 2024. The Author(s).)

Introduction: The systems of dietary and body that favor the prevention and control of type 2 diabetes (T2D) go against what is vital for most of the migrant population, exposing them to conflicts of norms that are difficult to reconcile. The purpose of this scoping review is to identify factors that may influence the acceptance or rejection of dietary and body norm systems favorable to the prevention and control of T2D by sub-Saharan Africa migrants living with T2D., Methods: An electronic search of studies from 2011 to 2022, published in English, Italian, French, or Portuguese was conducted in seven databases and in gray literature. The selection of articles was done independently and blindly by six teams of two researchers in accordance with the inclusion and exclusion criteria defined by the PICO., Results: Seven studies were included. The results show several factors influencing the acceptance or rejection of dietary and body norms systems favorable to the prevention and control of T2D among the migrants from sub-Saharan Africa, mainly social network, income, availability, and affordability of foods, among others., Conclusion: Given the paucity of studies available on factors influencing the acceptance or rejection of body norm systems favorable to the prevention and control of T2D by sub-Saharan Africa migrants living with T2D, further studies are needed to better document these factors. A better understanding of these factors and their influence on the well-being of migrant people from sub-Saharan Africa living with T2D could help guide policy, research, and interventions so that they are better adapted to the realities of these populations., (© 2024. W. Montague Cobb-NMA Health Institute.)

There are many healthcare financing programs (HFPs) in Cameroon; however, there is a lack of information on these programs' economic effectiveness and efficiency. Involvement of local stakeholders in the economic evaluations (EEs) of HFPs is critical for ensuring contextual factors are considered prior to program implementation. We conducted a cross-sectional study to assess the need for EEs of Cameroonian HFPs. Regular staff in supervisory roles aged 18 years and above were recruited in four Cameroonian cities. Data were collected via face-to-face surveys between June 15 and August 1, 2022. Descriptive analyses summarized participants' knowledge, attitudes, and practices in relation to performing EEs of HFPs. Principal component analyses identified organizational, individual, and contextual factors that could influence participants' involvement. The total sample included 106 participants. On average, 65% of participants reported being aware of the listed HFPs; however, of these, only 28% said that they had been involved in the HFPs. Of the 106 participants, 57.5% knew about EEs; yet, almost 90% reported that the HFP in question had never been subject to an EE, and 84% had never been involved in an EE. Most participants indicated that they had intended or would like to receive EE training. Using principal component analyses, the organizational factors were classified into two components ('policy and governance' and 'planning and implementation'), the individual factors were classified into two components ('training' and 'motivation'), and the contextual factors were classified into three components ('funding,' 'political economy,' and 'public expectations'). The findings of this study highlight the need to invest in EE training to improve participation rates of Cameroonian stakeholders in the EEs of HFPs. Improved knowledge, diversified skills, and increased participation of stakeholders from all levels of the Cameroonian healthcare system are critical to the effective and efficient development, implementation, and EE of the country's HFPs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tchouaket et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Cytotoxic agents are the cornerstone of treatment for patients with advanced intrahepatic cholangiocarcinoma (iCCA), despite heterogeneous benefit. We hypothesised that the pretreatment molecular profiles of diagnostic biopsies can predict patient benefit from chemotherapy and define molecular bases of innate chemoresistance., Design: We identified a cohort of advanced iCCA patients with comparable baseline characteristics who diverged as extreme outliers on chemotherapy (survival <6 m in rapid progressors, RP; survival >23 m in long survivors, LS). Diagnostic biopsies were characterised by digital pathology, then subjected to whole-transcriptome profiling of bulk and geospatially macrodissected tissue regions. Spatial transcriptomics of tumour-infiltrating myeloid cells was performed using targeted digital spatial profiling (GeoMx). Transcriptome signatures were evaluated in multiple cohorts of resected cancers. Signatures were also characterised using in vitro cell lines, in vivo mouse models and single cell RNA-sequencing data., Results: Pretreatment transcriptome profiles differentiated patients who would become RPs or LSs on chemotherapy. Biologically, this signature originated from altered tumour-myeloid dynamics, implicating tumour-induced immune tolerogenicity with poor response to chemotherapy. The central role of the liver microenviroment was confrmed by the association of the RPLS transcriptome signature with clinical outcome in iCCA but not extrahepatic CCA, and in liver metastasis from colorectal cancer, but not in the matched primary bowel tumours., Conclusions: The RPLS signature could be a novel metric of chemotherapy outcome in iCCA. Further development and validation of this transcriptomic signature is warranted to develop precision chemotherapy strategies in these settings., Competing Interests: Competing interests: JBA is a member of the scientific advisory board at SEALD, Norway and reports scientific consultancies for QED Therapeutics and Flagship Pioneering. JBA has received research funding from Incyte. CB received honoraria as speaker (Astrazeneca, Incyte) and consultant (Incyte, Servier, Boehringer Ingelheim, Astrazeneca), received research funds (Avacta, Medannex, Servier) and her spouse is an employee of Astrazeneca. JML is receiving research support from Eisai, Bayer HealthCare Pharmaceuticals, Ipsen, and consulting fees from Eisai, Merck, Bristol-Myers Squibb, Eli Lilly, Roche, Genentech, Ipsen, Glycotest, AstraZeneca, Bayer HealthCare Pharmaceuticals, Omega Therapeutics, Mina Alpha, Boston Scientific, Exelixis, Bluejay and Captor Therapeutics. RM has received consulting and lecture fees from Servier and Roche and travel and education funding from MSD, Eli Lilly, Bayer, Roche, Astrazeneca. AL reports receiving consulting fees from Intercept Pharma, Alfa Sigma, Takeda, and Albireo Pharma, and speakers’ fees from Gilead, Abbvie, MSD, Intercept Pharma, AlfaSigma, GSK and Incyte., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Diet, physical activity, and body shape play an essential role in the development of type 2 diabetes (T2D) and are the social dimensions most targeted by health professionals in their practices or intervention aimed at preventing and controlling T2D. However, several interventions focus more on individual factors and less on social determinants likely to influence the adoption of dietary, body, and physical activity standards favorable to the prevention and control of T2D. This study aims to explore the social determinants influencing the rejection or adoption of dietary, bodily, and physical activity norms favorable to the prevention and control of T2D among migrants from sub-Saharan Africa. A qualitative exploratory design guided data collection and analysis. Semi-structured qualitative interviews and focus groups were conducted between October 2022 and March 2023 in Montreal and Quebec Cities. The cost of food, the difficulty of accessing certain foods, a reliable level of income, work schedules, the gazes of relatives or communities, migration policies, disappointment and stressful situations linked to migratory status, racial microaggressions, and the lack of food guides adapted to the realities of MASS were the main determinants identified by the participants. These determinants can influence the adoption of public health recommendations on diet for the prevention and control of T2D. People living with T2D obviously have an important role to play, but much of the work lies outside their control. Therefore, Preventive, clinical, or awareness-raising interventions should more consider the life and structural contexts in which these people navigate without ignoring their pre-migratory rules of dietary, body, and physical activity norms., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: We present two atypical cases of calciphylaxis presenting with ocular ischemic pathology - both without the hallmark cutaneous manifestations - to raise awareness of this rare yet highly disabling condition., Observations: We report two cases of ophthalmic calciphylaxis presenting as (1) anterior ischemic optic neuropathy (AION) and cilioretinal artery occlusion in a 76-year-old woman with pre-dialysis kidney failure, and (2) AION with contralateral central retinal artery occlusion (CRAO) in a 44-year-old man on hemodialysis., Conclusion and Importance: These cases highlight the need for judicious clinical suspicion of calciphylaxis in patients with kidney failure, presenting with microvascular ischemic ophthalmic pathology such as AION or CRAO. Confirmation with temporal artery biopsy is essential to direct targeted individualized multi-disciplinary treatment of calciphylaxis and avoid unnecessary steroid exposure in cases masquerading as giant cell arteritis (GCA)., Competing Interests: The authors have no conflict of interest to declare. Table 1Summary of literature describing ocular calciphylaxis. CaseSex/AgeSymptomsOcular diseaseOther sites involvedRenal diseaseLaboratory resultsCutaneous/temporal artery biopsyTreatmentCase 1: Awwad et al. (2010) [12]Male, 75 yearsBlurred vision in left eye Painful dusky skin lesions over bilateral calvesLeft AIONSkin: dusky purpuric plaques (confirmed calciphylaxis on skin biopsy) on bilateral calvesType 2 diabetes mellitus (on insulin) ESRD on peritoneal dialysis Coronary artery disease (on warfarin) HypertensionESR 106 mm/h Calcium 7.7 mg/dL Phosphorus 9.5 mg/dL Creatinine 12.3 mg/mLDiffuse and extensive circumferential calcification at the internal elastic lamina and media, minimal inflammation, no granulomaPrednisolone 80 mg prior to diagnosis of calciphylaxis Further treatment not detailed in reportCase 2: Chehade et al. (2020) [16]Male, 67 yearsPainless left visual decline over 24 hours Fluid overloadLeft AION and BRAOHeart: nodular mass on posterior mitral valve leaflet – fibroelastoma with calcification No cutaneous involvementType I diabetes mellitus Ischemic heart disease NSTEMI and coronary artery bypass graft Hypertension Peripheral vascular disease Bilateral critical limb ischemia with below-knee amputation ESRDESR 49 mm/h CRP 26 mg/L Urea 29.6 mmol/L Creatinine 415 μmol/L Calcium 2.01 mmol/L Platelets × 109/LExtensive circumferential calcification, intimal swelling and luminal narrowing, occasional multinucleate giant cells, no background granulomatous inflammationIV methylprednisolone 3 days then oral prednisolone whilst awaiting TAB Hemodialysis commenced CinacalcetCase 3: Cherayil et al. (2021) [22]Female, 72 yearsBilateral vision loss Preceding painful gluteal nodules – biopsy-confirming calcinosis cutisBilateral ischemic optic neuropathy and ocular ischemic syndrome (R > L) Left crystalline maculopathySkin: calcinosis cutis of bilateral gluteal musclesESRD: Membranous glomerulonephritis Failed renal transplant Peritoneal dialysis Type 2 diabetes Hypertension with systolic heart failureSerum correct calcium 9.4 mg/dLPhosphate 12.8 mg/dL Calcium-phosphate product 120.3 mg2/dL2PTH 1,365 pg/mL Creatinine 16.70 mg/dL Serum oxalate 23.0 μmol/LTAB not performed Calciphylaxis diagnosed on skin biopsy (calcinosis cutis) and clinical findingsIV sodium thiosulfate through hemodialysisCase 4: Danset et al. (2021) [25]Male, 67 yearsPainful glans penis, painful skin lesions on bilateral thighs and necrotic calf ulcerLeft CRAOSkin: glans penis gangrenous ulceration, bilateral panniculitis of the thighs and calf ulcerType 2 diabetes Hypertension Arrhythmic cardiomyopathy Dyslipidemia Obesity ESRD (IgA glomerulonephritis), on peritoneal dialysisPTH 294 ng/L Normal calcium phosphate 2.23 mmol/LNot performed Calciphylaxis diagnosed on skin biopsyHemodialysis IV sodium thiosulfateRheopheresis Discontinuation of fluindione and vitamin DCase 5: Farooqui et al. (2019) [9]Male, 39 yearsSudden painless vision loss left eyeLeft AIONNil No cutaneous involvementESRD (glomerulonephritis), on hemodialysisESR 120 mm/h CRP 74.1 mg/L Negative vasculitis work-up Normal platelet count Serum phosphate 1.72 mmol/L Low total calcium 1.55 mmol/L Normal PTH 2.1 pmol/LCalcification of the medial and severe luminal occlusion, no inflammatory findings, no giant cellsShort oral steroids with rapid taper after TAB IV sodium thiosulphate with hemodialysisCase 6: Hanna et al. (2015) [23]Male, 64 yearsSevere abdominal pain, acute anuria, confusion Then 3 months later, sudden left eye blindnessLeft ophthalmic artery occlusionSkin: lower limb popular lesions (biopsy provide calcinosis) Genitalia: glans penis dry gangrene (biopsy-confirmed calciphylaxis), testicular microliths Renal: acute tubular necrosis, microlithsHypertension Type 2 diabetes Congestive cardiac failure (systolic) Chronic renal disease stage 3 (diabetic glomerulosclerosis)Serum creatinine 6 mL/min/1.73m2 (eGFR 6) Potassium 7.4 mmol/L Urea 178 mg/dL Corrected calcium 10.2 mg/dL Phosphorous 13.5 mg/dL Calcium phosphorous product 121.5 mg2/dL2HIV/hepatitis serology negative ANA/ANCA negative PTH 612 pg/mL Negative vasculitis screenSkin biopsy calcinosisHemodialysis IV piperacillin/tazobactam for penile gangrene Partial penectomyCase 7: Hepschke et al. 2019 [21]Male, 78 yearsSudden-onset painless reduced right vision, with preceding non-healing necrotic leg ulcersRight CRAO and AIONSkin: non-healing necrotic leg ulcersHypertension Hyperlipidemia Ischemic heart disease Atrial fibrillation (on warfarin) CABG Aortic valve replacement Gout ESRD (on hemodialysis) Carotid and vertebral artery stenosis (80 – 99%)Platelets 219 × 109/L ESR 102 mm/h CRP 98 mg/L CT brain: diffuse calcification of vessels MRI brain: changes of chronic microvascular disease, no focal cerebral ischemia “borderline elevated calcium and phosphate” eGFR 13 mL/min/1.73 m2TAB: focal myxoid degeneration and extensive concentric calcium deposition in the tunica media, no features of GCAIV methylprednisolone whilst awaiting TAB Hyperbaric oxygen Hemodialysis with low calcium replacement fluids Cessation of vitamin D supplementation Warfarin ceased and changed to LMWH and aspirinCase 8: Huerva et al. (2011) [13]Female, 51 yearsBilateral sequential vision lossSequential bilateral AIONSkin: necrotic cutaneous lesions at the distal phalanges of right-hand fingersESRD (sclerosis tuberose and bilateral nephrectomy) – on hemodialysis Secondary hyperparathyroidism (subtotal parathyroidectomy)Normal vasculitic screen (ANCA, ACA assays) Syphilis serology negative Normal albumin, vitamin B12, folic acid, immunoglobins and cryoglobulins ESR 70 mm/hSkin biopsy: calcification in the wall of small artery TAB: large calcium deposits in the artery tunica mediaIV methylprednisolone for 3 days then oral steroids for 2 months Hemodialysis Surgical debridement of skin lesions and hyperbaric oxygenCase 9: Komurcu et al. (2016) [20]Female, 43 yearsSudden-onset visual impairmentBilateral AIONSkin: acral gangrene (bilateral hands and feet) Visceral ischemia (mesenteric, spleen, renal)ESRD (on hemodialysis)Normal ESR/CRP Negative vasculitis, autoimmune and infectious screen Serum calcium 8.8 mg/dL (normal) Phosphorus 12.5 mg/dL PTH 137 pg/mLThumb amputation: calcification, thrombi, obstructive endovascular fibrotic areas in the walls of arteriesIV methylprednisolone then oral steroids (up to 15 days) Pentoxifylline Acetylsalicylic acid HemodialysisCase 10: Korzets et al. (2004) [11]Patient 1: Male, 77 yearsRight eye vision lossRight AIONWidespread arterial wall calcifications No cutaneous involvementHypertension Type 2 diabetes mellitus ESRD (on hemodialysis) Ischemic heart disease with previous myocardial infarction Peripheral vascular disease (toe amputation) Aortic valve replacement (on warfarin) Widespread arterial calcificationsSerum phosphorous 10 mg/dL Serum PTH 950 pg/mLTAB: profound medial calcificationsIV methylprednisolone (ceased after 5 days)Patient 2: Female, 70 yearsBitemporal headaches with blurred vision in inferior right visual fieldRight AIONNil No cutaneous involvementHemodialysis IgG γ-monoclonal gammopathy of undetermined significance Atherosclerosis Myocardial infarction with CABG Peripheral vascular disease with left below-knee amputation Bilateral cataract surgerySerum phosphorous 10 mg/dL PTH < 100 pg/mLTAB: concentric medial calcification, with no features of arteritisIV methylprednisolone (ceased after 4 days)Case 11: Mishra et al. (2021) [11]Female, 58 yearsBilateral reduced visionRetinal arteriolar calcification with ischemic retinopathyNil No cutaneous involvementESRD (obstructive uropathy from staghorn calculi) Right percutaneous nephrolithotomy with stent Not on dialysisUrea 123 mg/dL Creatinine 12.9 mg/dL Calcium 8.2 mg/dL Phosphate 7.3 mg/dL PTH 233.8 pg/mL Vitamin D3 26.96 ng/dL Calcium phosphate product 59.86 mg2/dL2eGFR 26 mL/min/1.73m2Not reportedPan retinal photocoagulationCase 12: Naysan et al. (2018) [6]Male, 65 yearsPoor vision bilaterallyBilateral crystalline retinopathy with prior right CRAOSkin: necrotic skin lesions of upper thigh (prior to ocular symptoms)ESRD (obstructive nephropathy from nephrolithiasis, on hemodialysis)Normal range corrected total serum calcium and phosphorus levelsSkin biopsy: medial arterial wall calcification and necrosis of the skin epithelium confirming calciphylaxisNot reportedCase 13: Roverano et al. (2015) [8]Female, 82 yearsSudden vision loss in left eye No headache, jaw claudication, proximal muscle weakness, weight lossOcular: AIONNil No cutaneous involvementNot reported (non-uremic calciphylaxis – no prior history of ESRD)ESR 62 mm/h Urea 0.56 g/dL Serum creatinine 1.7 mg/dL Low calcium (8.39 mg%) and phosphorus (2.40 mg/dL)Normal urine calcium (74 mg/24h) Normal PTH (51.41 pg/mL) Autoimmune/vasculitic screen normal (anticardiolipins, lupus anticoagulant, ANCA, IgG and subtypes)TAB: large calcium deposits in the artery’s tunica media and internal elastic lamina, luminal narrowing, no inflammation nor multinuclear giant cellsIV methylprednisolone then oral prednisolone (ceased upon TAB findings confirming calciphylaxis)Case 14: Shah et al. (2012) [17]Male 72 yearsSudden vision loss in left eye, then right eye 3 days laterOcular: Bilateral sequential AIONSkin: widespread dusky skin plaques that became gangrenous (limbs and glans penis) – onset after ocular symptomsESRD (on peritoneal dialysis) Hypertension Diabetes mellitus Aortic valve replacement (aortic stenosis, on warfarin) Atrial fibrillation CCF Tricuspid regurgitation Pulmonary hypertension Left ventricular hypertrophy Diabetic retinopathy and nephropathyBUN 69 mg/dL Creatinine 6.3 mg/dL GFR 9 mL/min/1.73 m2Calcium 7.9 mg/dL Phosphorus 6.6 mg/dL Calcium phosphate product 51.48 mg/dL PTH 164 pg/mLTAB: large coarse marked calcifications in the muscular artery with no evidence of vasculitis Skin biopsies: calciphylaxis, with prominent calcification of the small vessels in the subcutaneous fat with ischemic necrosis and ulceration of the overlying epidermisIV steroids (ceased following TAB results) Hemodialysis commenced Calcium acetate stopped and replaced with sevelamer (non-calcium phosphate binder)Case 15: Sivertsen et al. (2018) [19]Female 72 years Reduced vision left eye No headache, jaw claudication, or symptoms of polymyalgia rheumatica Prior painful leg ulcers with recurrent bacterial infectionsOcular: left AIONSkin: leg ulcersHTN AF (on warfarin) Type 2 diabetes mellitus Rheumatoid arthritis No prior history of ESRD (non-uremic calciphylaxis)ESR 57 mm/h CRP 28 mg/L Corrected calcium 2.56 mmol/L Phosphate 1.36 mmol/L Creatinine 33 μmol/L PTH 3.5 pmol/LTAB: extensive medial and intimal calcification consistent with calciphylaxis, no features of arteritisIV sodium thiosulfate AF = atrial fibrillation; AION = arteritic ischemic optic neuropathy; ANA = antinuclear antibody; ANCA = antineutrophil cytoplasmic antibody; BRAO = branch retinal artery occlusion; BUN = blood urea nitrigen; CABG = coronary artery bypass graft; CCF = congestive cardiac failure; CRAO = central retinal artery occlusion; CRP = c-reactive protein; eGFR = estimated glomerular filtration rate; ESR = erythrocyte sedimentation rate; ESRD = end-stage renal disease; GCA = giant cell arteritis; GFR = glomerular filtration rate; HTN = hypertension; IV = intravenous; LMWH = low molecular weight heparin; PTH = parathyroid hormone; RAPD = relative afferent pupillary defect; TAB = temporal artery biopsy. Figure 7Temporal artery biopsy showing extensive circumferential calcification of the media with some associated intimal hyperplasia.Figure 1Color fundus photo of the left eye showing optic nerve head swelling, cotton wool spots along the cilioretinal artery distribution, and background moderate non-proliferative diabetic retinopathy.Figure 2Fundus fluorescein angiography (FFA) at (A) 17 seconds showing nasal choroidal non-perfusion and (B) 5 minutes, showing disc leakage and late staining at the cilioretinal artery distribution.Figure 3Temporal artery biopsy showing severe calcification and marked intimal thickening within the media and outer intima.Figure 4Color fundus photos demonstrating right circumferential (A) optic disc swelling with small superior disc flame hemorrhage and left (B) inferior pallid disc swelling, widespread retinal pallor with a cherry-red macula suggestive of central retinal artery occlusion.Figure 5Spectral domain optical coherence tomography (SD-OCT) scans of the macula, demonstrating right (A) nasal Retinal nerve fibre layer (RNFL) thickening not involving the macula with normal foveal contour and (B) left macula hyper-reflectivity with signal increase and loss of distinction of the inner retinal layers.Figure 6Fundus fluorescein angiography (FA) delayed choroidal filling with disc hyper-fluorescence and late patchy venous staining in the right eye (A) and delayed choroidal filling and delayed arteriovenous transit time in the left eye (B)., (© Dustri-Verlag Dr. K. Feistle.)

Access to universal health coverage is a fundamental right that ensures that even the most disadvantaged receive health services without financial hardship. The Democratic Republic of Congo is among the poorest countries in the world, yet healthcare is primarily made by direct payment which renders care inaccessible for most Congolese. Between 2017 and 2021 a purchasing of health services initiative (Le Programme de Renforcement de l'Offre et Développement de l'accès aux Soins de Santé or PRO DS), was implemented in Kongo Central and Ituri with the assistance of the non-governmental organization Memisa Belgium. The program provided funding for health system strengthening that included health service delivery, workforce development, improved infrastructure, access to medicines and support for leadership and governance. This study assessed the social and health impacts of the PRO DS Memisa program using a health impact assessment focus. A documentary review was performed to ascertain relevant indicators of program effect. Supervision and management of health zones and health centers, use of health and nutritional services, the population's nutritional health, immunization levels, reproductive and maternal health, and newborn and child health were measured using a controlled longitudinal model. Positive results were found in almost all indicators across both provinces, with a mean proportion of positive effect of 60.8% for Kongo Central, and 70.8% in Ituri. Barriers to the program's success included the arrival of COVID-19, internal displacement of the population and resistance to change from the community. The measurable positive impacts from the PRO DS Memisa program reveal that an adequately funded multi-faceted health system strengthening program can improve access to healthcare in a low-income country such as the Democratic Republic of Congo., (© 2023. The Author(s).)