A rare canonical splice-site variant in VPS13B causes attenuated Cohen syndrome

Background: To describe a patient with a history of obesity, retinal dystrophy, type II diabetes, and mild cognitive impairment; found to harbour biallelic splice-site variants in VPS13B. // Materials & methods: A complete ophthalmic evaluation was performed at Moorfields Eye Hospital (London, United Kingdom), consisting of measurement of best-corrected visual acuity (BCVA), slit lamp and dilated fundus evaluation, colour, autofluorescence and near-infrared retinal imaging, spectral domain-optical coherence tomography, and electroretinogram (ERG). Whole-genome sequencing was performed as part of the UK’s 100,000 Genomes Project. // Results: A 26-year-old Pakistani man with normal appearance, stature, and head size presented with decreased BCVA and severely constricted visual fields to our Ophthalmic Genetics clinic. He had a history of obesity, type II diabetes, and mild cognitive impairment. His evaluation showed retina-wide, severe photoreceptor dysfunction in both eyes, with undetectable scotopic and photopic ERG waveforms. Genomic analysis identified a homozygous rare splice donor variant in the VPS13B gene (c.5024+2T>C) that was demonstrated to lead to skipping of the in-frame exon 31 (p.Gln1607_Ser1675delinsHis). // Conclusions: Exon 31 skipping in VPS13B may lead to a hypomorphic change, with partial gene function and an incomplete, mild Cohen syndrome-like phenotype

Hazard Analysis of Critical Control Points Assessment as a Tool to Respond to Emerging Infectious Disease Outbreaks

Highly pathogenic avian influenza virus (HPAI) strain H5N1 has had direct and indirect economic impacts arising from direct mortality and control programmes in over 50 countries reporting poultry outbreaks. HPAI H5N1 is now reported as the most widespread and expensive zoonotic disease recorded and continues to pose a global health threat. The aim of this research was to assess the potential of utilising Hazard Analysis of Critical Control Points (HACCP) assessments in providing a framework for a rapid response to emerging infectious disease outbreaks. This novel approach applies a scientific process, widely used in food production systems, to assess risks related to a specific emerging health threat within a known zoonotic disease hotspot. We conducted a HACCP assessment for HPAI viruses within Vietnam’s domestic poultry trade and relate our findings to the existing literature. Our HACCP assessment identified poultry flock isolation, transportation, slaughter, preparation and consumption as critical control points for Vietnam’s domestic poultry trade. Introduction of the preventative measures highlighted through this HACCP evaluation would reduce the risks posed by HPAI viruses and pressure on the national economy. We conclude that this HACCP assessment provides compelling evidence for the future potential that HACCP analyses could play in initiating a rapid response to emerging infectious diseases

Making optical atomic clocks more stable with 10−1610^{-16} level laser stabilization

The superb precision of an atomic clock is derived from its stability. Atomic clocks based on optical (rather than microwave) frequencies are attractive because of their potential for high stability, which scales with operational frequency. Nevertheless, optical clocks have not yet realized this vast potential, due in large part to limitations of the laser used to excite the atomic resonance. To address this problem, we demonstrate a cavity-stabilized laser system with a reduced thermal noise floor, exhibiting a fractional frequency instability of $2 \times 10^{-16}$. We use this laser as a stable optical source in a Yb optical lattice clock to resolve an ultranarrow 1 Hz transition linewidth. With the stable laser source and the signal to noise ratio (S/N) afforded by the Yb optical clock, we dramatically reduce key stability limitations of the clock, and make measurements consistent with a clock instability of $5 \times 10^{-16} / \sqrt{\tau}$

Availability, formulation, labelling, and price of low-sodium salts worldwide

BACKGROUND: Regular salt is about 100% sodium chloride (NaCl). Low-sodium salts have reduced sodium chloride content, most commonly through substitution with potassium chloride (KCl). Low-sodium salts have a potential role in reducing population sodium intake level and blood pressure, but its availability in global market was unknown. OBJECTIVE: The aim of this study was to assess the availability, formulation, labelling, and price of low-sodium salts currently available to consumers around the world. METHODS: Low-sodium salts were identified through a systematic literature review, Google search, online shopping sites search, and inquiry of key informants. The keywords of "salt substitute", "low-sodium salt", "potassium salt", "mineral salt", and "sodium reduced salt" in six official languages of the United Nations were used for search. Information about the brand, formula, labelling, and price was extracted and analysed. RESULTS: Eighty-seven low-sodium salts were available in 47 out of 195 countries around the world (24%), including 28 high-income countries, 13 upper-middle-income countries, and six lower-middle-income countries. The proportion of sodium chloride varied from 0% (sodium-free) to 88% (as percent of weight, regular salt is 100% NaCl). Potassium chloride was the most frequent another component with levels ranging from 0% to 100% (potassium chloride salt). Forty-three (49%) had labels advising potential health risk, 33 (38%) labelling the advice of potential health benefits. The median price of low-sodium salts in high-income, upper-middle-income, lower-middle-income countries was USD 15.0/kg (IQR: 6.4 to 22.5), USD 2.7/kg (IQR: 1.7 to 5.5) and USD 2.9/kg (IQR: 0.50 to 22.2) respectively. The price of low-sodium salts was between 1.1 and 14.6 times that of regular salts. CONCLUSIONS: Low-sodium salts are not widely available and are commonly more expensive than regular salts. Policies that promote the availability, affordability and labelling of low-sodium salts should enhance appropriate uptake for blood pressure lowering and cardiovascular prevention. CLINICALTRIAL: INTERNATIONAL REGISTERED REPORT: RR2-10.1111/jch.14054

A large-scale study of a poultry trading network in Bangladesh: implications for control and surveillance of avian influenza viruses

Since its first report in 2007, avian influenza (AI) has been endemic in Bangladesh. While live poultry marketing is widespread throughout the country and known to influence AI dissemination and persistence, trading patterns have not been described. The aim of this study is to assess poultry trading practices and features of the poultry trading networks which could promote AI spread, and their potential implications for disease control and surveillance. Data on poultry trading practices was collected from 849 poultry traders during a cross-sectional survey in 138 live bird markets (LBMs) across 17 different districts of Bangladesh. The quantity and origins of traded poultry were assessed for each poultry type in surveyed LBMs. The network of contacts between farms and LBMs resulting from commercial movements of live poultry was constructed to assess its connectivity and to identify the key premises influencing it

Sensitivity and Specificity of Multiple Kato-Katz Thick Smears and a Circulating Cathodic Antigen Test for Schistosoma mansoni Diagnosis Pre- and Post-repeated-Praziquantel Treatment

Two Kato-Katz thick smears (Kato-Katzs) from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This ‘gold standard’ has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA) is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E) and drug-efficacy findings

Bayesian paternity analysis and mating patterns in a parasitic nematode, Trichostrongylus tenuis

Mating behaviour is a fundamental aspect of the evolutionary ecology of sexually reproducing species, but one that has been under-researched in parasitic nematodes. We analysed mating behaviour in the parasitic nematode Trichostrongylus tenuis by performing a paternity analysis in a population from a single red grouse host. Paternity of the 150 larval offspring of 25 mothers (sampled from one of the two host caeca) was assigned among 294 candidate fathers (sampled from both caeca). Each candidate father's probability of paternity of each offspring was estimated from 10-locus microsatellite genotypes. Seventy-six (51%) offspring were assigned a father with a probability of >0.8, and the estimated number of unsampled males was 136 (95% credible interval (CI) 77-219). The probability of a male from one caecum fathering an offspring in the other caecum was estimated as 0.024 (95% CI 0.003-0.077), indicating that the junction of the caeca is a strong barrier to dispersal. Levels of promiscuity (defined as the probability of two of an adult's offspring sharing only one parent) were high for both sexes. Variance in male reproductive success was moderately high, possibly because of a combination of random mating and high variance in post-copulatory reproductive success. These results provide the first data on individual mating behaviour among parasitic nematodes

Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans

A model to control the epidemic of H5N1 influenza at the source

<p>Abstract</p> <p>Background</p> <p>No country is fully prepared for a 1918-like pandemic influenza. Averting a pandemic of H5N1 influenza virus depends on the successful control of its endemicity, outbreaks in poultry and occasional spillage into human which carries a case-fatality rate of over 50%. The use of perimetric depopulation and vaccination has failed to halt the spread of the epidemic. Blanket vaccination for all poultry over a large geographical area is difficult. A combination of moratorium, segregation of water fowls from chickens and vaccination have been proved to be effective in the Hong Kong Special Administrative Region (HKSAR) since 2002 despite endemicity and outbreaks in neighbouring regions. Systematic surveillance in southern China showed that ducks and geese are the primary reservoirs which transmit the virus to chickens, minor poultry and even migratory birds.</p> <p>Presentation of the hypothesis</p> <p>We hypothesize that this combination of moratorium, poultry segregation and targeted vaccination if successfully adapted to an affected district or province in any geographical region with high endemicity would set an example for the control in other regions.</p> <p>Testing the hypothesis</p> <p>A planned one-off moratorium of 3 weeks at the hottest month of the year should decrease the environmental burden as a source of re-infection. Backyard farms will then be re-populated by hatchlings from virus-free chickens and minor poultry only. Targeted immunization of the ducks and geese present only in the industrial farms and also the chickens would be strictly implemented as blanket immunization of all backyard poultry is almost impossible. Freely grazing ducks and geese would not be allowed until neutralizing antibodies of H5 subtype virus is achieved. As a proof of concept, a simple mathematical model with susceptible-infected-recovered (SIR) structure of coupled epidemics between aquatic birds (mainly ducks and geese) and chickens was used to estimate transmissibility within and between these two poultry populations. In the field the hypothesis is tested by prospective surveillance of poultry and immunocompetent patients hospitalized for severe pneumonia for the virus before and after the institution of these measures.</p> <p>Implications of the Hypothesis</p> <p>A combination of targeted immunization with the correct vaccine, segregation of poultry species and moratorium of poultry in addition to the present surveillance, biosecurity and hygienic measures at the farm, market and personal levels could be important in the successful control of the H5N1 virus in poultry and human for an extensive geographical region with continuing outbreaks. Alternatively a lesser scale of intervention at the district level can be considered if there is virus detection without evidence of excess poultry deaths since asymptomatic shedding is common in waterfowls.</p