An unusual presentation of a catecholamine producing tumour

In patients with pheochromocytomas it is well known that differentfactors can precipitate an acute pheochromocytoma crisis. Our patient presented with a vesicular skin rash and respiratory distress suggestive of disseminated varicella zoster for which he was treated with steroids and acyclovir. Two days later hypertension was noted for the first time

Implementation of an ST-Segment Elevation Myocardial Infraction Bypass Protocol in the Northern United Arab Emirates

Objective: The aim was to evaluate the translation of an ST-segment elevation myocardial infraction (STEMI) bypass protocol to the outcomes of patients with acute coronary syndrome in the Emirate of Ras al-Khaimah in the United Arab Emirates (UAE). Methods: A prospective cohort study was conducted, which included all patients who had a prehospital 12-lead electrocardiogram (ECG) performed by ambulance crews. Analysis of those who were identified as having STEMI and who subsequently underwent percutaneous coronary intervention (PCI) was performed. Results: A total of 152 patients had a 12-lead ECG performed during the pilot study period (February 24, 2016-August 31, 2016) with 118 included for analysis. Mean patient age was 52 years. There were 87 male (74%) and 31 female (26%) patients. Twenty-nine patients suffered a STEMI, and data were available for 11 who underwent PCI. There was no mortality, and no major adverse cardiac events were reported. The median door-to-balloon (D2B) time was 73 min (range 48-124), and 81% of patients had a D2B time \u3c90 min. Discharge data were available for six patients: All were discharged home with no impediments to rehabilitation. Conclusion: This pilot study has demonstrated agreement with the existing literature surrounding prehospital ECG and PCI activation in an unstudied STEMI population and in a novel clinical setting. It has demonstrated a D2B time of \u3c90 min in over 80% of STEMI patients, and a faster mean D2B time than self-presentations (mean 77 min vs. 113 min), with no associated mortality or major adverse cardiac events

Ending malnutrition in all its forms requires scaling up proven nutrition interventions and much more: a 129-country analysis.

BackgroundSustainable Development Goal (SDG) 2.2 calls for an end to all forms of malnutrition, with 2025 targets of a 40% reduction in stunting (relative to 2012), for wasting to occur in less than 5% of children, and for a 50% reduction in anaemia in women (15-49 years). We assessed the likelihood of countries reaching these targets by scaling up proven interventions and identified priority interventions, based on cost-effectiveness.MethodsFor 129 countries, the Optima Nutrition model was used to compare 2019-2030 nutrition outcomes between a status quo (maintained intervention coverage) scenario and a scenario where outcome-specific interventions were scaled up to 95% coverage over 5 years. The average cost-effectiveness of each intervention was calculated as it was added to an expanding package of interventions.ResultsOf the 129 countries modelled, 46 (36%), 66 (51%) and 0 (0%) were on track to achieve the stunting, wasting and anaemia targets respectively. Scaling up 18 nutrition interventions increased the number of countries reaching the SDG 2.2 targets to 50 (39%), 83 (64%) and 7 (5%) respectively. Intermittent preventative treatment of malaria during pregnancy (IPTp), infant and young child feeding education, vitamin A supplementation and lipid-based nutrition supplements for children produced 88% of the total impact on stunting, with average costs per case averted of US$103, US$267, US$556 and US$1795 when interventions were consecutively scaled up, respectively. Vitamin A supplementation and cash transfers produced 100% of the total global impact on prevention of wasting, with average costs per case averted of US$1989 and US$19,427, respectively. IPTp, iron and folic acid supplementation for non-pregnant women, and multiple micronutrient supplementation for pregnant women produced 85% of the total impact on anaemia prevalence, with average costs per case averted of US$9, US$35 and US$47, respectively.ConclusionsPrioritising nutrition investment to the most cost-effective interventions within the country context can maximise the impact of funding. A greater focus on complementing nutrition-specific interventions with nutrition-sensitive ones that address the social determinants of health is critical to reach the SDG targets

The use of dexamethasone in women with preterm premature rupture of membranes - A multicentre, double-blind, placebocontrolled, randomised trial

No Abstract

Changes in Retinol-Binding Protein Concentrations and Thyroid Homeostasis with Nonoccupational Exposure to DDT

BACKGROUND: The insecticide dichlorodiphenyltrichloroethane (DDT) has been used for malaria vector control in the northern and eastern parts of the Vhembe District of Limpopo Province, South Africa, since 1945. Bioaccumulation of DDT raises concern because it reportedly affects thyroid function. OBJECTIVE: Our objective was to investigate the association between DDT uptake (as reflected in plasma concentrations) and thyroid homeostasis while considering related factors. METHODS: We compared dietary intake, serum retinol-binding protein (RBP), transthyretin (TTR) and albumin concentrations, and liver and thyroid function between cases with evidence of a body burden of DDT in the circulation (concentration of any DDT isomer ≥ 0.02 μg/g lipid; n = 278) and controls (concentration of all DDT isomers < 0.02 μg/g lipid; n = 40) in a cross-sectional study. Further analyses were performed to assess the relevance of changes in RBP status associated with DDT uptake. RESULTS: RBP concentrations below the reference range were more prevalent in cases (54% vs. 10% in controls; χ2 = 27.4; p < 0.001), which could not be explained by nutrient intake. We observed significantly lower thyroid hormone concentrations among cases (p ≤ 0.01). We also observed a significant linear trend for serum concentrations of free thyroxine and free triiodothyronine (p < 0.001) and a significant quadratic trend for serum thyroid-stimulating hormone (p = 0.025) and TTR (p < 0.001) across the control group and case groups with normal and relatively low RBP concentrations. Relatively low RBP concentrations were associated with significantly higher DDT and 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) isomer concentrations and with a higher DDE/DDT ratio (p ≤ 0.01), which signifies long-term exposure. Inadequate intake of vitamin A and zinc were observed in 84% and 58%, respectively, of the total study population. CONCLUSION: RBP concentrations appear to decrease in the presence of long-term DDT uptake, which may have deleterious effects on thyroid function and vitamin A nutritional status. This is of major concern in a population with poor vitamin A and zinc intake

Prevalence and Determinants of Vitamin D Deficiency in 1825 Cape Town Primary Schoolchildren: A Cross-Sectional Study

Vitamin D deficiency (25-hydroxyvitamin D[25(OH)D] &lt;50 nmol/L) is common among adults in Cape Town, South Africa, but studies investigating vitamin D status of children in this setting are lacking. We conducted a cross-sectional study to determine the prevalence and determinants of vitamin D deficiency in 1825 Cape Town schoolchildren aged 6&ndash;11 years. Prevalence of vitamin D deficiency was 7.6% (95% Confidence Interval [CI] 6.5% to 8.9%). Determinants of vitamin D deficiency included month of sampling (adjusted odds ratio [aOR] for July&ndash;September vs. January&ndash;March 10.69, 95% CI 5.02 to 22.77; aOR for October&ndash;December vs. January&ndash;March 6.73, 95% CI 2.82 to 16.08), older age (aOR 1.25 per increasing year, 95% CI: 1.01&ndash;1.53) and higher body mass index (BMI; aOR 1.24 per unit increase in BMI-for-age Z-score, 95% CI: 1.03&ndash;1.49). In a subset of 370 participants in whom parathyroid hormone (PTH) concentrations were measured; these were inversely related to serum 25(OH)D concentrations (p &lt; 0.001). However, no association between participants with hyperparathyroidism (PTH &gt;6.9 pmol/L) and vitamin D deficiency was seen (p = 0.42). In conclusion, we report that season is the major determinant of vitamin D status among Cape Town primary schoolchildren, with prevalence of vitamin D deficiency ranging from 1.4% in January&ndash;March to 22.8% in July&ndash;September

Experimental evidence indicating that mastreviruses probably did not co-diverge with their hosts

Background. Despite the demonstration that geminiviruses, like many other single stranded DNA viruses, are evolving at rates similar to those of RNA viruses, a recent study has suggested that grass-infecting species in the genus Mastrevirus may have co-diverged with their hosts over millions of years. This "co-divergence hypothesis" requires that long-term mastrevirus substitution rates be at least 100,000-fold lower than their basal mutation rates and 10,000-fold lower than their observable short-term substitution rates. The credibility of this hypothesis, therefore, hinges on the testable claim that negative selection during mastrevirus evolution is so potent that it effectively purges 99.999% of all mutations that occur. Results. We have conducted long-term evolution experiments lasting between 6 and 32 years, where we have determined substitution rates of between 2 and 3 × 10 -4substitutions/site/year for the mastreviruses Maize streak virus (MSV) and Sugarcane streak Réunion virus (SSRV). We further show that mutation biases are similar for different geminivirus genera, suggesting that mutational processes that drive high basal mutation rates are conserved across the family. Rather than displaying signs of extremely severe negative selection as implied by the co-divergence hypothesis, our evolution experiments indicate that MSV and SSRV are predominantly evolving under neutral genetic drift. Conclusion. The absence of strong negative selection signals within our evolution experiments and the uniformly high geminivirus substitution rates that we and others have reported suggest that mastreviruses cannot have co-diverged with their hosts. © 2009 Harkins et al; licensee BioMed Central Ltd

Evolutionary distances in the twilight zone -- a rational kernel approach

Phylogenetic tree reconstruction is traditionally based on multiple sequence alignments (MSAs) and heavily depends on the validity of this information bottleneck. With increasing sequence divergence, the quality of MSAs decays quickly. Alignment-free methods, on the other hand, are based on abstract string comparisons and avoid potential alignment problems. However, in general they are not biologically motivated and ignore our knowledge about the evolution of sequences. Thus, it is still a major open question how to define an evolutionary distance metric between divergent sequences that makes use of indel information and known substitution models without the need for a multiple alignment. Here we propose a new evolutionary distance metric to close this gap. It uses finite-state transducers to create a biologically motivated similarity score which models substitutions and indels, and does not depend on a multiple sequence alignment. The sequence similarity score is defined in analogy to pairwise alignments and additionally has the positive semi-definite property. We describe its derivation and show in simulation studies and real-world examples that it is more accurate in reconstructing phylogenies than competing methods. The result is a new and accurate way of determining evolutionary distances in and beyond the twilight zone of sequence alignments that is suitable for large datasets.Comment: to appear in PLoS ON

Molecular evolution of HoxA13 and the multiple origins of limbless morphologies in amphibians and reptiles

Developmental processes and their results, morphological characters, are inherited through transmission of genes regulating development. While there is ample evidence that cis-regulatory elements tend to be modular, with sequence segments dedicated to different roles, the situation for proteins is less clear, being particularly complex for transcription factors with multiple functions. Some motifs mediating protein-protein interactions may be exclusive to particular developmental roles, but it is also possible that motifs are mostly shared among different processes. Here we focus on HoxA13, a protein essential for limb development. We asked whether the HoxA13 amino acid sequence evolved similarly in three limbless clades: Gymnophiona, Amphisbaenia and Serpentes. We explored variation in ω (dN/dS) using a maximum-likelihood framework and HoxA13sequences from 47 species. Comparisons of evolutionary models provided low ω global values and no evidence that HoxA13 experienced relaxed selection in limbless clades. Branch-site models failed to detect evidence for positive selection acting on any site along branches of Amphisbaena and Gymnophiona, while three sites were identified in Serpentes. Examination of alignments did not reveal consistent sequence differences between limbed and limbless species. We conclude that HoxA13 has no modules exclusive to limb development, which may be explained by its involvement in multiple developmental processes