Genetic characterization of human coxsackievirus A6 variants associated with atypical hand, foot and mouth disease: a potential role of recombination in emergence and pathogenicity

Human coxsackievirus A6 (CVA6) is an enterically transmitted enterovirus. Until recently, CVA6 infections were considered as being of minor clinical significance, and only rarely aetiologically linked with hand, foot and mouth disease (HFMD) associated with other species A enteroviruses (particularly EV71 and CVA16). From 2008 onwards, however, CVA6 infections have been associated with several outbreaks worldwide of atypical HFMD (aHFMD) accompanied by a varicelliform rash. We recently reported CVA6-associated eczema herpeticum occurring predominantly in children and young adults in Edinburgh in January and February 2014. To investigate genetic determinants of novel clinical phenotypes of CVA6, we genetically characterized and analysed CVA6 variants associated with eczema herpeticum in Edinburgh in 2014 and those with aHFMD in CAV isolates collected from 2008. A total of eight recombinant forms (RFs) have circulated worldwide over the past 10 years, with the particularly recent appearance of RF-H associated with eczema herpeticum cases in Edinburgh in 2014. Comparison of phylogenies and divergence of complete genome sequences of CVA6 identified recombination breakpoints in 2A-2C, within VP3, and between 5' untranslated region and VP1. A Bayesian temporal reconstruction of CVA6 evolution since 2004 provided estimates of dates and the actual recombination events that generated more recently appearing recombination groups (RF-E, -F, -G and -H). Associations were observed between recombination groups and clinical presentations of herpangina, aHFMD and eczema herpeticum, but not with VP1 or other structural genes. These observations provided evidence that NS gene regions may potentially contribute to clinical phenotypes and outcomes of CVA6 infection

Global competencies in family medicine

Introduction:This project was devised to provide a global snapshot of required national competencies in Family Medicine, and is the result of an international collaboration of the International Fellowship of Primary Care Research Networks (IFPCRN). The Research team, which devised the questionnaire and original list of competencies, was drawn from around 30 countries and 15 countries responded to the questionnaire and contributed national data. These countries however represented close to two thirds of our global population and included Low, Middle and High Income countries (based on World Bank Purchasing price Parity (PPP) 2005) as well Parity (PPP) 2005) as well as representing a good cross section of climatological, socio economic and geographical situations. Aims and Objectives: To compile a list of competencies required of global family doctors, via global consultation, and use them in the form of a questionnaire to survey national family medicine representatives to ascertain if family doctors are required to be competent in these disciplines. The Objective is to provide a ‘global snapshot’ of competencies and trends in family medicine Materials and Methods: A representative list of family medicine competencies was compiled by an International Fellowship of Primary Care Research Networks (IFPCRN) group, from 30 countries over a 3-month period, commencing June 2009. A list of 57 expanded items, and 44 core items was then compiled and formed the basis of a questionnaire, with provision for adding additional competencies that did not appear in the list of 57. This was broadcast by list server to the IFPCRN email group. Results: 15 Family medicine/ primary care representatives completed the survey on behalf of their nation (or region in the case of West Africa). Results showed a trend toward a globally standard curriculum but still much variation in competencies taught

Genotyping of clinically relevant human adenoviruses by array-in-well hybridization assay

AbstractA robust oligonucleotide array-in-well hybridization assay using novel up-converting phosphor reporter technology was applied for genotyping clinically relevant human adenovirus types. A total of 231 adenovirus-positive respiratory, ocular swab, stool and other specimens from 219 patients collected between April 2010 and April 2011 were included in the study. After a real-time PCR amplification targeting the adenovirus hexon gene, the array-in-well assay identified the presence of B03 (n = 122; 57.5% of patients), E04 (29; 13.7%), C02 (21; 9.9%), D37 (14; 6.6%), C01 (12; 5.7%), C05 (5; 2.4%), D19 (4; 1.9%), C06 (2; 0.9%), D08 (1; 0.5%), A31 (1; 0.5%) and F41 (1; 0.5%) genotypes among the clinical sample panel. The typing result was obtained for all specimens that could be amplified (n = 223; 97%), and specificity of the typing was confirmed by sequencing specimens representing each of the different genotypes. No hybridization signal was obtained in adenovirus-negative specimens or specimens with other viruses (n = 30). The array-in-well hybridization assay has great potential as a rapid and multiplex platform for the typing of clinically relevant human adenovirus genotypes in different specimen types

Attenuated Semliki Forest virus for cancer treatment in dogs : safety assessment in two laboratory Beagles

Background: Dogs suffer from spontaneous tumors which may be amenable to therapies developed for human cancer patients, and dogs may serve as large-animal cancer models. A non-pathogenic Semliki Forest virus vector VA7-EGFP previously showed promise in targeting human tumor xenografts in mice, but the oncolytic capacity of the virus in canine cancer cells and the safety of the virus in higher mammals such as dogs, are not known. We therefore assessed the oncolytic potency of VA7-EGFP against canine cancer cells by infectivity and viability assays in two dog solid tumor cell lines. Furthermore we performed a 3-week safety study in two adult Beagles which received a single intravenous injection of similar to 2 x 10(5) plaque forming units of parental A7(74) strain. Results: VA7-EGFP was able to replicate in and kill both canine cancer cell lines tested. No adverse events were observed in either of the two virus-injected adult Beagles and no infective virus could be recovered from any of the biological samples collected over the course of the study. Neutralizing antibodies to Semliki Forest virus became detectable in the dogs at 5 days post infection and remained elevated until study termination. Conclusions: Based on these results, testing of the oncolytic potential of attenuated Semliki Forest virus in canine cancer patients appears feasible.Peer reviewe

Isolated entrapment of the brachialis branch of the musculocutaneous nerve: a case report

Non peer reviewe

RANDOMISED DOUBLE BLIND STUDY TO COMPARE EFFECTIVENESS OF HONEY, SALBUTAMOL AND PLACEBO IN TREATMENT OF COUGH IN CHILDREN WITH COMMON COLD

Background: Acute upper respiratory infection is the most common childhood illness and presents with cough, coryza and fever. Available evidence suggests that cough medicines may be no more effective than honey-based cough remedies. Objective: To compare effectiveness of honey, salbutamol and placebo in the treatment of cough in children with acute onset cough. Design: Randomised control trial Setting: Aga Khan University Hospital Paediatric Casualty Subjects: Children between ages one to twelve years presenting with a common cold between December 2010 and February 2012 were enrolled. Outcome measures: Frequency, severity and extent to which cough bothered and disturbed child and parental sleep were assessed at baseline and over the subsequent five days through telephone interview using a validated scoring tool. Results: One hundred and forty five children were enrolled in the study (45- placebo, 57 –honey, 43 –salbutamol). Of the 145 children 51% were male. Honey significantly reduced the total mean symptom score by day three (p\u3c 0.001). Total mean difference in scores between day zero to five demonstrated a significant difference of honey’s efficacy over placebo (p\u3c 0.002) however no difference was noted when compared to salbutamol (p\u3c0.478). Significant differences in both total as well as each individual symptom score was detected with honey consistently scoring the best whilst placebo and salbutamol scored the worst. In paired comparisons honey was superior to placebo but not salbutamol, whilst salbutamol was not superior to placebo. Conclusion: Honey was most effective in symptomatic relief of symptoms associated with the common cold whilst salbutamol or placebo offered no benefit

Nutritional considerations during prolonged exposure to a confined, hyperbaric, hyperoxic environment: Recommendations for saturation divers

Saturation diving is an occupation that involves prolonged exposure to a confined, hyperoxic, hyperbaric environment. The unique and extreme environment is thought to result in disruption to physiological and metabolic homeostasis, which may impact human health and performance. Appropriate nutritional intake has the potential to alleviate and/or support many of these physiological and metabolic concerns, whilst enhancing health and performance in saturation divers. Therefore, the purpose of this review is to identify the physiological and practical challenges of saturation diving and consequently provide evidence-based nutritional recommendations for saturation divers to promote health and performance within this challenging environment. Saturation diving has a high-energy demand, with an energy intake of between 44 and 52 kcal/kg body mass per day recommended, dependent on intensity and duration of underwater activity. The macronutrient composition of dietary intake is in accordance with the current Institute of Medicine guidelines at 45-65 % and 20-35 % of total energy intake for carbohydrate and fat intake, respectively. A minimum daily protein intake of 1.3 g/kg body mass is recommended to facilitate body composition maintenance. Macronutrient intake between individuals should, however, be dictated by personal preference to support the attainment of an energy balance. A varied diet high in fruit and vegetables is highly recommended for the provision of sufficient micronutrients to support physiological processes, such as vitamin B12 and folate intake to facilitate red blood cell production. Antioxidants, such as vitamin C and E, are also recommended to reduce oxidised molecules, e.g. free radicals, whilst selenium and zinc intake may be beneficial to reinforce endogenous antioxidant reserves. In addition, tailored hydration and carbohydrate fueling strategies for underwater work are also advised

The right to health of non-nationals and displaced persons in the sustainable development goals era: challenges for equity in universal health care

Introduction: Under the Millennium Development Goals (MDGs), United Nations (UN) Member States reported progress on the targets toward their general citizenry. This focus repeatedly excluded marginalized ethnic and linguistic minorities, including people of refugee backgrounds and other vulnerable non-nationals that resided within a States’ borders. The Sustainable Development Goals (SDGs) aim to be truly transformative by being made operational in all countries, and applied to all, nationals and non-nationals alike. Global migration and its diffuse impact has intensified due to escalating conflicts and the growing violence in war-torn Syria, as well as in many countries in Africa and in Central America. This massive migration and the thousands of refugees crossing borders in search for safety led to the creation of two-tiered, ad hoc, refugee health care systems that have added to the sidelining of non-nationals in MDG-reporting frameworks. Conclusion: We have identified four ways to promote the protection of vulnerable non-nationals’ health and well being in States’ application of the post-2015 SDG framework: In setting their own post-2015 indicators the UN Member States should explicitly identify vulnerable migrants, refugees, displaced persons and other marginalized groups in the content of such indicators. Our second recommendation is that statisticians from different agencies, including the World Health Organization’s Gender, Equity and Human Rights programme should be actively involved in the formulation of SDG indicators at both the global and country level. In addition, communities, civil society and health justice advocates should also vigorously engage in country’s formulation of post-2015 indicators. Finally, we advocate that the inclusion of non-nationals be anchored in the international human right to health, which in turn requires appropriate financing allocations as well as robust monitoring and evaluation processes that can hold technocratic decision-makers accountable for progress.publishedVersio