Peptic ulcer

The probable explanation of the development of a chronic peptic ulcer is that there is a lowering of local vitality. Important amongst numerous predisposing causes for this are faulty diet and nervous strain. Described types of organisms either attack the stomach and duodenum before such a devitilisation or more likely after it. The acid of the stomach tends to keep the ulcer open and to counteract a tendency for spontaneous cure. As Judd has truly remarked, "The final word concerning (the pathogenesis of) gastric and duodenal ulcer has not been spoken". Diagnosis rests particularly on two considerations. The first consideration is that following a careful clinical examination where especial note is made of the history. The second is a consideration of an X-ray examination. When operation has been advised or a post-mortem has been made, the excellence of modern radiology is proved, I have no regrets for basing my diagnosis so essentially on this ancillary science. Claims that a proper etiological basis had been found, led to the administration of histidine. Its use has been very doubtful, if not useless. A recent successful treatment of haematemesls has been described. The mortality rate is not high. The future health and working capacity of the individual is frequently impaired. Gastric acidity must be neutralised or buffered. Thus diet, alkalies and buffering agents are necessary. A reasonable proportion of cases does well. Relapses are likely in the present state of our knowledge. Routine treatments are useful. Physicians and Surgeons are co-operating to obtain a higher proportion of cures. There must, however, be a decided change from general treatment of the disease, to the individual study of the patient, and his circumstances

Documenting and visualising progress towards Universal Health Coverage of insulin and blood glucose test strips for people with diabetes.

AIMS: Global governments have committed to achieve Universal Health Coverage (UHC), ensuring access to quality and affordable healthcare for all. This is fundamental for those with type 1 diabetes mellitus, who require daily access to both insulin and blood glucose test strips to survive. This group risks being left behind by global initiatives that fail to consider these particular needs. METHODS: A questionnaire was distributed to key informants in 37 less-resourced countries. Seven high-income countries were also included for comparison. We drew on a WHO framework developed to assess progress towards UHC to create scales on three dimensions: population covered, services provided and direct costs. A fourth dimension, availability, was added. Results were grouped into six patterns and visually displayed with radar graphs. RESULTS: 65% of the less-resourced national health systems provided insulin, with medians of 67% for service provision (equating to Human Regular and NPH), 55% direct costs covered, and 75% availability. Test strips were only provided in 14% of the less-resourced systems, with medians 42% (less than two strips per day), 76%, and 88% respectively. Six patterns of provision were identified. Progress correlated with income level, yet some low-income countries are achieving provision for insulin and test strips for those enrolled in health insurance schemes. CONCLUSION: No less-resourced country had even near-complete coverage for insulin, and coverage was worse for test strips. This study demonstrates the utility of this framework which could be developed as a means of tracking progress in meeting the needs of people with diabetes

Perceived impact of the COVID-19 pandemic on young adults with type 1 diabetes in Rwanda

Introduction: data on the impact of COVID-19 on people with type 1 diabetes (T1D) in less resourced countries are limited. Our study was undertaken in Kigali, Rwanda, and aimed to investigate and describe the problems and challenges experienced by young adults with T1D resulting from the early phase of the pandemic. The study further aimed to understand the mechanisms being used to solve problems and overcome challenges, and perceived support needs. Methods: this was a cross-sectional study, with anonymous data (n=52) collected through use of questionnaire. Participants were registered, and attending or receiving diabetes-related healthcare through the Rwanda Diabetes Association clinic. Results: mean+standard deviation age and T1D duration were 24.0±2.1 and 7.4±3.4 years respectively, with sex distribution unequal (male n=22, 42.3%). Of 43 participants, the COVID-19 pandemic did not significantly affect participants´ access to diabetes management supplies and care. Eight (18.6%) participants experienced difficulties accessing blood glucose testing strips, 13 (30.2%) insulin, and three (7.0%) syringes and pen devices. Thirty-two (74.4%) experienced difficulty in attending standard diabetes healthcare reviews at the clinic setting. Some participants experienced hardship, through a decrease in personal or family income (n=42, 80.8%) and challenges in accessing food (n=34, 65.4%), with thirty (57.7%) participants having decreased meal frequency (p<0.001). Conclusion: our research illustrates the indirect effects of measures undertaken to curb the spread of COVID-19 on young adults with T1D in Rwanda. Study findings may help inform actions to mitigate negative impacts on T1D care in other crises

Ability of verbal autopsy data to detect deaths due to uncontrolled hyperglycaemia:testing existing methods and development and validation of a novel weighted score

Objectives: Verbal autopsy (VA) is a useful tool to ascertain cause of death where no other mechanisms exist. We aimed to assess the utility of VA data to ascertain deaths due to uncontrolled hyperglycaemia and to develop a weighted score (WS) to specifically identify cases. Cases were identified by a study or site physician with training in diabetes. These diagnoses were also compared with diagnoses produced by a standard computer algorithm (InterVA-4). Setting: This study was done using VA data from the Health and Demographic Survey sites in Agincourt in rural South Africa. Validation of the WS was done using VA data from Karonga in Malawi. Participants: All deaths from ages 1 to 49 years between 1992 and 2015 and between 2002 and 2016 from Agincourt and Karonga, respectively. There were 8699 relevant deaths in Agincourt and 1663 in Karonga. Results: Of the Agincourt deaths, there were 77 study physician classified cases and 58 computer algorithm classified cases. Agreement between study physician classified cases and computer algorithm classified cases was poor (Cohen’s kappa 0.14). Our WS produced a receiver operator curve with area under the curve of 0.952 (95% CI 0.920 to 0.985). However, positive predictive value (PPV) was below 50% when the WS was applied to the development set and the score was dominated by the necessity for a premortem diagnosis of diabetes. Independent validation showed the WS performed reasonably against site physician classified cases with sensitivity of 86%, specificity of 99%, PPV of 60% and negative predictive value of 99%. Conclusion: Our results suggest that widely used VA methodologies may be missing deaths due to uncontrolled hyperglycaemia. Our WS may offer improved ability to detect deaths due to uncontrolled hyperglycaemia in large populations studies where no other means exist

Diabetes in sub-Saharan Africa: from clinical care to health policy.

Rapid demographic, sociocultural, and economic transitions are driving increases in the risk and prevalence of diabetes and other non-communicable diseases (NCDs) in sub-Saharan Africa. The impacts of these transitions and their health and economic consequences are evident. Whereas, in 1990, the leading causes of death in sub-Saharan Africa were HIV/AIDS, lower respiratory infections, diarrhoeal diseases, malaria, and vaccine-preventable diseases in children, in more recent years, cardiovascular diseases and their risk factors are replacing infectious diseases as the leading causes of death in this region, and rates of increase of cardiovascular risk factors are predicted to be greater in sub-Saharan Africa than in other parts of the world. Thus, sub-Saharan Africa—which contains a high proportion of the world\u27s least developed countries—will face the multifaceted challenge of dealing with a high burden of infectious diseases and diseases of poverty, while also addressing the increasing burden of cardiovascular disease and its risk factors. At present, many of the health systems in sub-Saharan Africa struggle to cope with infectious diseases. Meeting the goals of the UN high-level meeting on NCDs (to reduce premature mortality from NCDs by 25% by 2025) and Sustainable Development Goals (SDGs; to reduce premature mortality from NCDs by a third by 2030) requires a coordinated approach within countries, which starts with a firm consideration of disease burden, needs, and priorities

A Korean Family with the Muenke Syndrome

The Muenke syndrome (MS) is characterized by unicoronal or bicoronal craniosynostosis, midfacial hypoplasia, ocular hypertelorism, and a variety of minor abnormalities associated with a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. The birth prevalence is approximately one in 10,000 live births, accounting for 8-10% of patients with coronal synostosis. Although MS is a relatively common diagnosis in patients with craniosynostosis syndromes, with autosomal dominant inheritance, there has been no report of MS, in an affected Korean family with typical cephalo-facial morphology that has been confirmed by molecular studies. Here, we report a familial case of MS in a female patient with a Pro250Arg mutation in exon 7 (IgII-IGIII linker domain) of the FGFR3 gene. This patient had mild midfacial hypoplasia, hypertelorism, downslanting palpebral fissures, a beak shaped nose, plagio-brachycephaly, and mild neurodevelopmental delay. The same mutation was confirmed in the patient's mother, two of the mother's sisters and the maternal grandfather. The severity of the cephalo-facial anomalies was variable among these family members

Analysing reduced tillage practices within a bio-economic modelling framework

Sustainable Intensification of agricultural production systems will require changes in farm practice. Within arable cropping systems, reducing the intensity of tillage practices (e.g. reduced tillage) potentially offers one such sustainable intensification approach. Previous researchers have tended to examine the impact of reduced tillage on specific factors such as yield or weed burden, while, by definition, sustainable intensification necessitates a system-based analysis approach. Drawing upon a bio-economic optimisation model, ‘MEETA’, we quantify trade-off implications between potential yield reductions, reduced cultivation costs and increased crop protection costs. We extend the MEETA model to quantify farm-level net margin, in addition to quantifying farm-level gross margin, net energy, and greenhouse gas emissions. For the lowest intensity tillage system, zero tillage, results demonstrate financial benefits over a conventional tillage system even when the zero tillage system includes yield penalties of 0-14.2% (across all crops). Average yield reductions from zero tillage literature range from 0-8.5%, demonstrating that reduced tillage offers a realistic and attainable sustainable intensification intervention, given the financial and environmental benefits, albeit that yield reductions will require more land to compensate for loss of calories produced, negating environmental benefits observed at farm-level. However, increasing uptake of reduced tillage from current levels will probably require policy intervention; an extension of the recent changes to the CAP (‘Greening’) provides an opportunity to do this

Endocrine Activity of Extraembryonic Membranes Extends beyond Placental Amniotes

BACKGROUND. During development, all amniotes (mammals, reptiles, and birds) form extraembryonic membranes, which regulate gas and water exchange, remove metabolic wastes, provide shock absorption, and transfer maternally derived nutrients. In viviparous (live-bearing) amniotes, both extraembryonic membranes and maternal uterine tissues contribute to the placenta, an endocrine organ that synthesizes, transports, and metabolizes hormones essential for development. Historically, endocrine properties of the placenta have been viewed as an innovation of placental amniotes. However, an endocrine role of extraembryonic membranes has not been investigated in oviparous (egg-laying) amniotes despite similarities in their basic structure, function, and shared evolutionary ancestry. In this study, we ask whether the oviparous chorioallantoic membrane (CAM) of chicken (Gallus gallus) has the capability to synthesize and receive signaling of progesterone, a major placental steroid hormone. METHODOLOGY/PRINCIPAL FINDINGS. We quantified mRNA expression of key steroidogenic enzymes involved in progesterone synthesis and found that 3β-hydroxysteroid dehydrogenase, which converts pregnenolone to progesterone exhibited a 464 fold increase in the CAM from day 8 to day 18 of embryonic development (F5, 68=89.282, p<0.0001). To further investigate progesterone synthesis, we performed explant culture and found that the CAM synthesizes progesterone in vitro in the presence of a steroid precursor. Finally, we quantified mRNA expression and performed protein immunolocalization of the progesterone receptor in the CAM. CONCLUSIONS/SIGNIFICANCE. Collectively, our data indicate that the chick CAM is steroidogenic and has the capability to both synthesize progesterone and receive progesterone signaling. These findings represent a paradigm shift in evolutionary reproductive biology by suggesting that endocrine activity of extraembryonic membranes is not a novel characteristic of placental amniotes. Rather, we hypothesize that these membranes may share an additional unifying characteristic, steroidogenesis, across amniotes at large.Sigma Xi (G20073141634396861); National Science Foundation (2008059161); UF-Howard Hughes G.A.T.O.R. Program; Howard Hughes Medical Institute Professorshi

The Serum Proteome and Ursodeoxycholic Acid Response in Primary Biliary Cholangitis.

Funder: UK‐PBC MRC Stratified MedicineFunder: Pfizer; Id: http://dx.doi.org/10.13039/100004319BACKGROUND AND AIMS: Stratified therapy has entered clinical practice in primary biliary cholangitis (PBC), with routine use of second-line therapy in nonresponders to first-line therapy with ursodeoxycholic acid (UDCA). The mechanism for nonresponse to UDCA remains, however, unclear and we lack mechanistic serum markers. The UK-PBC study was established to explore the biological basis of UDCA nonresponse in PBC and identify markers to enhance treatment. APPROACH AND RESULTS: Discovery serum proteomics (Olink) with targeted multiplex validation were carried out in 526 subjects from the UK-PBC cohort and 97 healthy controls. In the discovery phase, untreated PBC patients (n = 68) exhibited an inflammatory proteome that is typically reduced in scale, but not resolved, with UDCA therapy (n = 416 treated patients). Nineteen proteins remained at a significant expression level (defined using stringent criteria) in UDCA-treated patients, six of them representing a tightly linked profile of chemokines (including CCL20, known to be released by biliary epithelial cells (BECs) undergoing senescence in PBC). All showed significant differential expression between UDCA responders and nonresponders in both the discovery and validation cohorts. A linear discriminant analysis, using serum levels of C-X-C motif chemokine ligand 11 and C-C motif chemokine ligand 20 as markers of responder status, indicated a high level of discrimination with an AUC of 0.91 (CI, 0.83-0.91). CONCLUSIONS: UDCA under-response in PBC is characterized by elevation of serum chemokines potentially related to cellular senescence and was previously shown to be released by BECs in PBC, suggesting a potential role in the pathogenesis of high-risk disease. These also have potential for development as biomarkers for identification of high-risk disease, and their clinical utility as biomarkers should be evaluated further in prospective studies