A Toolkit to assess health needs for congenital disorders in low- and middle-income countries: an instrument for public health action.

BACKGROUND: In 2010 the World Health Assembly called for action to improve the care and prevention of congenital disorders, noting that technical guidance would be required for this task, especially in low- and middle-income countries. Responding to this call, we have developed a freely available web-accessible Toolkit for assessing health needs for congenital disorders. METHODS: Materials for the Toolkit website (http://toolkit.phgfoundation.org) were prepared by an iterative process of writing, discussion and modification by the project team, with advice from external experts. A customized database was developed using epidemiological, demographic, socio-economic and health-services data from a range of validated sources. Document-processing and data integration software combines data from the database with a template to generate topic- and country-specific Calculator documents for quantitative analysis. RESULTS: The Toolkit guides users through selection of topics (including both clinical conditions and relevant health services), assembly and evaluation of qualitative and quantitative information, assessment of the potential effects of selected interventions, and planning and prioritization of actions to reduce the risk or prevalence of congenital disorders. CONCLUSIONS: The Toolkit enables users without epidemiological or public health expertise to undertake health needs assessment as a prerequisite for strategic planning in relation to congenital disorders in their country or region

Serum Calcium and the Risk of Breast Cancer: Findings from the Swedish AMORIS Study and a Meta-Analysis of Prospective Studies

To investigate the association between serum calcium and risk of breast cancer using a large cohort and a systematic review with meta-analysis. From the Swedish Apolipoprotein Mortality Risk (AMORIS) Study we included 229,674 women who had baseline measurements of serum total calcium and albumin. Multivariable Cox regression was used to assess the association between total and albumin-corrected calcium and breast cancer risk. For the systematic review, an electronic search of MEDLINE and EMBASE databases was performed to identify other prospective cohorts assessing the relationship between serum calcium and breast cancer risk. We pooled the results of our AMORIS cohort with other eligible studies in a meta-analysis using a random effects model. I² test was used to assess heterogeneity. In the AMORIS study, 10,863 women were diagnosed with breast cancer (mean follow-up: 19 years). We found an inverse association between total serum calcium and breast cancer when comparing the fourth quartile to the first quartile (HR: 0.94, 95% CI: 0.88-0.99, p value for trend 0.04) and similar results using albumin-corrected calcium. In the systematic review, we identified another two prospective cohorts evaluating pre-diagnostic serum total calcium and breast cancer. Combining these studies and our findings in AMORIS in a meta-analysis showed a protective effect of serum calcium against breast cancer, with a summary RR of 0.80 (95% CI: 0.66-0.97). No substantial heterogeneity was observed. Our findings in AMORIS and the meta-analysis support an inverse association between serum calcium and breast cancer risk, which warrants mechanistic investigations

Topical fluorouracil after surgery for ocular surface squamous neoplasia in Kenya: a randomised, double-blind, placebo-controlled trial

BACKGROUND: Ocular surface squamous neoplasia (OSSN) is an aggressive eye tumour particularly affecting people with HIV in Africa. Primary treatment is surgical excision; however, tumour recurrence is common. We assessed the effect of fluorouracil 1% eye drops after surgery on recurrence. METHODS: We did this multicentre, randomised, placebo-controlled trial in four centres in Kenya. We enrolled patients with histologically proven OSSN aged at least 18 years. After standard surgical excision, participants were randomly allocated to receive either topical fluorouracil 1% or placebo four times a day for 4 weeks. Randomisation was stratified by surgeon, and participants and trial personnel were masked to assignment. Patients were followed up at 1 month, 3 months, 6 months, and 12 months. The primary outcome was clinical recurrence (supported by histological assessment where available) by 1 year, and analysed by intention to treat. The sample size was recalculated because events were more common than anticipated, and trial enrolment was stopped early. The trial was registered with Pan-African Clinical Trials Registry (PACTR201207000396219). FINDINGS: Between August, 2012, and July, 2014, we assigned 49 participants to fluorouracil and 49 to placebo. Four participants were lost to follow-up. Recurrences occurred in five (11%) of 47 patients in the fluorouracil group and 17 (36%) of 47 in the placebo group (odds ratio 0·21, 95% CI 0·07–0·63; p=0·01). Adjusting for passive smoking and antiretroviral therapy had little effect (odds ratio 0·23; 95% CI 0·07–0·75; p=0·02). Adverse effects occurred more commonly in the fluorouracil group, although they were transient and mild. Ocular discomfort occurred in 43 of 49 patients in the fluorouracil group versus 36 of 49 in the placebo group, epiphora occurred in 24 versus five, and eyelid skin inflammation occurred in seven versus none. INTERPRETATION: Topical fluorouracil after surgery substantially reduced recurrence of OSSN, was well-tolerated, and its use recommended

Magnetic resonance investigation into the mechanisms involved in the development of high-altitude cerebral edema

Rapid ascent to high altitude commonly results in acute mountain sickness, and on occasion potentially fatal high-altitude cerebral edema. The exact pathophysiological mechanisms behind these syndromes remain to be determined. We report a study in which 12 subjects were exposed to a FiO2 = 0.12 for 22 h and underwent serial magnetic resonance imaging sequences to enable measurement of middle cerebral artery velocity, flow and diameter, and brain parenchymal, cerebrospinal fluid and cerebral venous volumes. Ten subjects completed 22 h and most developed symptoms of acute mountain sickness (mean Lake Louise Score 5.4; p < 0.001 vs. baseline). Cerebral oxygen delivery was maintained by an increase in middle cerebral artery velocity and diameter (first 6 h). There appeared to be venocompression at the level of the small, deep cerebral veins (116 cm3 at 2 h to 97 cm3 at 22 h; p < 0.05). Brain white matter volume increased over the 22-h period (574 ml to 587 ml; p < 0.001) and correlated with cumulative Lake Louise scores at 22 h (p < 0.05). We conclude that cerebral oxygen delivery was maintained by increased arterial inflow and this preceded the development of cerebral edema. Venous outflow restriction appeared to play a contributory role in the formation of cerebral edema, a novel feature that has not been observed previously

Prevalence of co-existent neoplasia in clinically diagnosed pterygia in a UK population

INTRODUCTION: Ocular surface squamous neoplasia (OSSN) and pterygia share risk factors and co-exist in only a minority of cases. Reported rates of OSSN in specimens sent as pterygium for histopathological analysis vary between 0% and nearly 10%, with the highest rates reported in countries with high levels of ultraviolet light exposure. As there is a paucity of data in European populations, the aim of this study was to report the prevalence of co-existent OSSN or other neoplastic disease in clinically suspected pterygium specimens sent to a specialist ophthalmic pathology service in London, United Kingdom. METHODS: We performed a retrospective review of sequential histopathology records of patients with excised tissue submitted as suspected “pterygium” between 1997 and 2021. RESULTS: In total, 2061 specimens of pterygia were received during the 24-year period, with a prevalence of neoplasia in those specimens of 0.6% (n = 12). On detailed review of the medical records of these patients, half (n = 6) had the pre-operative clinical suspicion of possible OSSN. Of those cases without clinical suspicion pre-operatively, one was diagnosed with invasive squamous cell carcinoma of the conjunctiva. CONCLUSION: In this study, rates of unexpected diagnoses are reassuringly low. These results may challenge accepted dogma, and influence future guidance for the indications for submitting non-suspicious pterygia for histopathological analysis

Warm climates of the past—a lesson for the future? This is one article from the Discussion Meeting Issue ‘Warm climates of the past—a lesson for the future?’ compiled and edited by Daniel J. Lunt, Harry Elderfield, Richard Pancost and Andy Ridgwell

This Discussion Meeting Issue of the Philosophical Transactions A had its genesis in a Discussion Meeting of the Royal Society which took place on 10–11 October 2011. The Discussion Meeting, entitled ‘Warm climates of the past: a lesson for the future?’, brought together 16 eminent international speakers from the field of palaeoclimate, and was attended by over 280 scientists and members of the public. Many of the speakers have contributed to the papers compiled in this Discussion Meeting Issue. The papers summarize the talks at the meeting, and present further or related work. This Discussion Meeting Issue asks to what extent information gleaned from the study of past climates can aid our understanding of future climate change. Climate change is currently an issue at the forefront of environmental science, and also has important sociological and political implications. Most future predictions are carried out by complex numerical models; however, these models cannot be rigorously tested for scenarios outside of the modern, without making use of past climate data. Furthermore, past climate data can inform our understanding of how the Earth system operates, and can provide important contextual information related to environmental change. All past time periods can be useful in this context; here, we focus on past climates that were warmer than the modern climate, as these are likely to be the most similar to the future. This introductory paper is not meant as a comprehensive overview of all work in this field. Instead, it gives an introduction to the important issues therein, using the papers in this Discussion Meeting Issue, and other works from all the Discussion Meeting speakers, as exemplars of the various ways in which past climates can inform projections of future climate. Furthermore, we present new work that uses a palaeo constraint to quantitatively inform projections of future equilibrium ice sheet change

Hygienic quality of dehydrated aromatic herbs marketed in Southern Portugal

Dehydrated aromatic herbs are highly valued ingredients, widely used at home level and by food processing industry, frequently added to a great number of recipes in the Mediterranean countries. Despite being considered low-moisture products and classified as GRAS, during pre and post-harvesting stages of production they are susceptible of microbial contamination. In Europe an increasing number of food recalls and disease outbreaks associated with dehydrated herbs have been reported in recent years. In this study the microbial quality of 99 samples of aromatic herbs (bay leaves, basil, coriander, oregano, parsley, Provence herbs, rosemary and thyme) collected from retails shops in the region of Algarve (Southern Portugal) was assessed. All the samples were tested by conventional methods and were assayed for the total count of aerobic mesophilic microorganisms, Salmonella spp., Escherichia coli, coagulase-positive staphylococci and filamentous fungi. Almost 50 % of the herbs did not exceed the aerobic mesophilic level of 104 CFU/g. The fungi count regarded as unacceptable (106 CFU/g) was not found in any of the tested herbs, while 84 % of the samples ranged from ≤102 to 104 CFU/g. No sample was positive for the presence of Salmonella spp., Escherichia coli and staphylococci. The results are in compliance with the European Commission criteria although they point out to the permanent need of surveillance on the good standards of handling/cooking practices as well as the importance of avoiding contamination at production, retailing and distribution. The microbiological hazards associated with the pathogenic and toxigenic microbiota of dried herbs remain as a relevant public health issue, due to the fact that they are added to foods not submitted to any following lethal procedure. Control measures should be adopted in order to ensure that all phases of their supply chain respect the food safety standards.FCT: UID/BIA/04325/2019.info:eu-repo/semantics/publishedVersio

Online Assessment of Applied Anatomy Knowledge: The Effect of Images on Medical Students' Performance

Anatomical examinations have been designed to assess topographical and/or applied knowledge of anatomy with or without the inclusion of visual resources such as cadaveric specimens or images, radiological images, and/or clinical photographs. Multimedia learning theories have advanced the understanding of how words and images are processed during learning. However, the evidence of the impact of including anatomical and radiological images within written assessments is sparse. This study investigates the impact of including images within clinically oriented single‐best‐answer questions on students' scores in a tailored online tool. Second‐year medical students (n = 174) from six schools in the United Kingdom participated voluntarily in the examination, and 55 students provided free‐text comments which were thematically analyzed. All questions were categorized as to whether their stimulus format was purely textual or included an associated image. The type (anatomical and radiological image) and deep structure of images (question referring to a bone or soft tissue on the image) were taken into consideration. Students scored significantly better on questions with images compared to questions without images (P < 0.001), and on questions referring to bones than to soft tissue (P < 0.001), but no difference was found in their performance on anatomical and radiological image questions. The coding highlighted areas of “test applicability” and “challenges faced by the students.” In conclusion, images are critical in medical practice for investigating a patient's anatomy, and this study sets out a way to understand the effects of images on students' performance and their views in commonly employed written assessments

High fat diet modifies the association of lipoprotein lipase gene polymorphism with high density lipoprotein cholesterol in an Asian Indian population

Background Single nucleotide polymorphisms (SNPs) in lipoprotein lipase gene (LPL) have been shown to influence metabolism related to lipid phenotypes. Dietary factors have been shown to modify the association between LPL SNPs and lipids; however, to date, there are no studies in South Asians. Hence, we tested for the association of four common LPL SNPs with plasma lipids and examined the interactions between the SNPs and dietary factors on lipids in 1,845 Asian Indians. Methods The analysis was performed in 788 Type 2 diabetes cases and 1,057 controls randomly chosen from the cross-sectional Chennai Urban Rural Epidemiological Study. Serum triacylglycerol (TAG), serum total cholesterol, and high-density lipoprotein cholesterol (HDL-C) were measured using a Hitachi-912 autoanalyzer (Roche Diagnostics GmbH, Mannheim, Germany). Dietary intake was assessed using a semi-quantitative food frequency questionnaire. The SNPs (rs1121923, rs328, rs4922115 and rs285) were genotyped by polymerase chain reaction followed by restriction enzyme digestion and 20% of samples were sequenced to validate the genotypes obtained. Statistical Package for Social Sciences for Windows version 22.0 (SPSS, Chicago, IL) was used for statistical analysis. Results After correction for multiple testing and adjusting for potential confounders, SNPs rs328 and rs285 showed association with HDL-C (P = 0.0004) and serum TAG (P = 1×10−5), respectively. The interaction between SNP rs1121923 and fat intake (energy %) on HDL-C (P = 0.003) was also significant, where, among those who consumed a high fat diet (28.4 ± 2.5%), the T allele carriers (TT + XT) had significantly higher HDL-C concentrations (P = 0.0002) and 30% reduced risk of low HDL-C levels compared to the CC homozygotes. None of the interactions on other lipid traits were statistically significant. Conclusion Our findings suggest that individuals carrying T allele of the SNP rs1121923 have increased HDL-C levels when consuming a high fat diet compared to CC homozygotes. Our finding warrants confirmation in prospective studies and randomized controlled trials