Incidence of Guillain-Barre syndrome among patients with Campylobacter infection: A general practice research database study

The association between Campylobacter infection and subsequent Guillain-Barre syndrome (GBS) has been well documented. To date, however, there exists no direct estimate of the incidence of GBS among patients with Campylobacter infection. Using the General Practice Research Database, we estimate the incidence of GBS in a cohort of patients presenting with Campylobacter enteritis to be 1.17/1000 person-years, a rate 77 times greater than that in the general population. The probability that an individual who develops Campylobacter enteritis will also develop GBS during the subsequent 2-month period is < 2/10,000

Mild iodine deficiency and thyroid disorders in Hong Kong.

OBJECTIVES: To review evidence of iodine deficiency and clinical thyroid disorders in Hong Kong. DATA SOURCES: Publications on local dietary iodine intake, the iodine content of local food items, and clinical thyroid problems in the Hong Kong population. DATA EXTRACTION: Data was extracted and evaluated independently by the authors. DATA SYNTHESIS: Iodine is an essential nutrient. Iodine deficiency can lead to goitre, hypothyroidism, mental deficiency, and impaired growth. It is now appreciated that determination of goitre incidence in children alone may grossly underestimate the problem of iodine deficiency in a population. In total, the evidence indicates that iodine deficiency exists in Hong Kong, leading to clinical problems of transient neonatal hypothyroidism, goitrogenesis, and thyroid disorders in pregnant women and neonates, as well as thyroid dysfunction in the elderly. CONCLUSION: A supplementation programme aimed at a relatively uniform iodine intake is recommended to avoid deficient or excessive iodine intake in subpopulations.published_or_final_versio

Quantum cryptography without detector vulnerabilities using optically-seeded lasers

© 2016 Macmillan Publishers Limited. All rights reserved. Security in quantum cryptography is continuously challenged by inventive attacks targeting the real components of a cryptographic set-up, and duly restored by new countermeasures to foil them. Owing to their high sensitivity and complex design, detectors are the most frequently attacked components. It was recently shown that two-photon interference from independent light sources can be used to remove any vulnerability from detectors. This new form of detection-safe quantum key distribution (QKD), termed measurement-device-independent (MDI), has been experimentally demonstrated but with modest key rates. Here, we introduce a new pulsed laser seeding technique to obtain high-visibility interference from gain-switched lasers and thereby perform MDI-QKD with unprecedented key rates in excess of 1 megabit per second in the finite-size regime. This represents a two to six orders of magnitude improvement over existing implementations and supports the new scheme as a practical resource for secure quantum communications.L. C. Comandar acknowledges personal support via the EPSRC funded CDT in Photonic Systems Development and Toshiba Research Europe Ltd

A Participatory Health Promotion Mobile App Addressing Alcohol Use Problems (The Daybreak Program): Protocol for a Randomized Controlled Trial

BACKGROUND: At-risk patterns of alcohol use are prevalent in many countries with significant costs to individuals, families, and society. Screening and brief interventions, including with Web delivery, are effective but with limited translation into practice to date. Previous observational studies of the Hello Sunday Morning approach have found that their unique Web-based participatory health communication method has resulted in a reduction of at-risk alcohol use between baseline and 3 months. The Hello Sunday Morning blog program asks participants to publicly set a personal goal to stop drinking or reduce their consumption for a set period of time, and to record their reflections and progress on blogs and social networks. Daybreak is Hello Sunday Morning's evidence-based behavior change program, which is designed to support people looking to change their relationship with alcohol. OBJECTIVE: This study aims to systematically evaluate different versions of Hello Sunday Morning's Daybreak program (with and without coaching support) in reducing at-risk alcohol use. METHODS: We will use a between groups randomized control design. New participants enrolling in the Daybreak program will be eligible to be randomized to receive either (1) the Daybreak program, including peer support plus behavioral experiments (these encourage and guide participants in developing new skills in the areas of mindfulness, connectedness, resilience, situational strategies, and health), or (2) the Daybreak program, including the same peer support plus behavioral experiments, but with online coaching support. We will recruit 467 people per group to detect an effect size of f=0.10. To be eligible, participants must be resident in Australia, aged =18 years, score =8 on the alcohol use disorders identification test (AUDIT), and not report prior treatment for cardiovascular disease. RESULTS: The primary outcome measure will be reduction in the AUDIT-Consumption (AUDIT-C) scores. Secondary outcomes include mental health (Kessler's K-10), days out of role (Kessler), alcohol consumed (measured with a 7-day drinking diary in standard 10 g drinks), and alcohol-related harms (CORE alcohol and drug survey). We will collect data at baseline and 1, 3, and 6 months and analyze them with random effects models, given the correlated data structure. CONCLUSIONS: A randomized trial is required to provide robust evidence of the impact of the online coaching component of the Daybreak program, including over an extended period

Enhancement of outflow facility in the murine eye by targeting selected tight-junctions of Schlemm's canal endothelia

The juxtacanalicular connective tissue of the trabecular meshwork together with inner wall endothelium of Schlemm’s canal (SC) provide the bulk of resistance to aqueous outflow from the anterior chamber. Endothelial cells lining SC elaborate tight junctions (TJs), down-regulation of which may widen paracellular spaces between cells, allowing greater fluid outflow. We observed significant increase in paracellular permeability following siRNA-mediated suppression of TJ transcripts, claudin-11, zonula-occludens-1 (ZO-1) and tricellulin in human SC endothelial monolayers. In mice claudin-11 was not detected, but intracameral injection of siRNAs targeting ZO-1 and tricellulin increased outflow facility significantly. Structural qualitative and quantitative analysis of SC inner wall by transmission electron microscopy revealed significantly more open clefts between endothelial cells treated with targeting, as opposed to non-targeting siRNA. These data substantiate the concept that the continuity of SC endothelium is an important determinant of outflow resistance, and suggest that SC endothelial TJs represent a specific target for enhancement of aqueous movement through the conventional outflow system

Effect of a 2-week interruption in methotrexate treatment versus continued treatment on COVID-19 booster vaccine immunity in adults with inflammatory conditions (VROOM study): a randomised, open label, superiority trial

BACKGROUND: Immunosuppressive treatments inhibit vaccine-induced immunity against SARS-CoV-2. We evaluated whether a 2-week interruption of methotrexate treatment immediately after the COVID-19 vaccine booster improved antibody responses against the S1 receptor-binding domain (S1-RBD) of the SARS-CoV-2 spike protein compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases. METHODS: We did an open-label, prospective, two-arm, parallel-group, multicentre, randomised, controlled, superiority trial in 26 hospitals in the UK. We recruited adults from rheumatology and dermatology clinics who had been diagnosed with an immune-mediated inflammatory disease (eg, rheumatoid arthritis, psoriasis with or without arthritis, axial spondyloarthritis, atopic dermatitis, polymyalgia rheumatica, and systemic lupus erythematosus) and who were taking low-dose weekly methotrexate (≤25 mg per week) for at least 3 months. Participants also had to have received two primary vaccine doses from the UK COVID-19 vaccination programme. We randomly assigned the participants (1:1), using a centralised validated computer randomisation program, to suspend methotrexate treatment for 2 weeks immediately after their COVID-19 booster (suspend methotrexate group) or to continue treatment as usual (continue methotrexate group). Participants, investigators, clinical research staff, and data analysts were unmasked, while researchers doing the laboratory analyses were masked to group assignment. The primary outcome was S1-RBD antibody titres 4 weeks after receiving the COVID-19 booster vaccine dose, assessed in the intention-to-treat population. This trial is registered with ISRCT, ISRCTN11442263; following the pre-planned interim analysis, recruitment was stopped early. FINDINGS: Between Sept 30, 2021 and March 3, 2022, we recruited 340 participants, of whom 254 were included in the interim analysis and had been randomly assigned to one of the two groups: 127 in the continue methotrexate group and 127 in the suspend methotrexate group. Their mean age was 59·1 years, 155 (61%) were female, 130 (51%) had rheumatoid arthritis, and 86 (34%) had psoriasis with or without arthritis. After 4 weeks, the geometric mean S1-RBD antibody titre was 22 750 U/mL (95% CI 19 314-26 796) in the suspend methotrexate group and 10 798 U/mL (8970-12 997) in the continue methotrexate group, with a geometric mean ratio (GMR) of 2·19 (95% CI 1·57-3·04; p<0·0001; mixed-effects model). The increased antibody response in the suspend methotrexate group was consistent across methotrexate dose, administration route, type of immune-mediated inflammatory disease, age, primary vaccination platform, and history of SARS-CoV-2 infection. There were no intervention-related serious adverse events. INTERPRETATION: A 2-week interruption of methotrexate treatment for people with immune-mediated inflammatory diseases resulted in enhanced boosting of antibody responses after COVID-19 vaccination. This intervention is simple, low-cost, and easy to implement, and could potentially translate to increased vaccine efficacy and duration of protection for susceptible groups. FUNDING: National Institute for Health and Care Research

Association of ICAM3 genetic variant with severe acute respiratory syndrome

Genetic polymorphisms have been demonstrated to be associated with vulnerability to human infection. ICAM3, an intercellular adhesion molecule important for T cell activation, and FCER2 (CD23), an immune response gene, both located on chromosome 19p13.3, were investigated for host genetic susceptibility and association with clinical outcome. A case-control study based on 817 patients with confirmed severe acute respiratory syndrome (SARS), 307 health care worker control subjects, 290 outpatient control subjects, and 309 household control subjects unaffected by SARS from Hong Kong was conducted to test for genetic association. No significant association to susceptibility to SARS infection caused by the novel coronavirus (SARS-CoV) was found for the FCER2 and the ICAM3 single nucleotide polymorphisms. However, patients with SARS homozygous for ICAM3 Gly143 showed significant association with higher lactate dehydrogenase levels (P = .0067; odds ratio [OR], 4.31 [95% confidence interval {CI}, 1.37-13.56]) and lower total white blood cell counts (P = .022; OR, 0.30 [95% CI, 0.10-0.89]) on admission. These findings support the role of ICAM3 in the immunopathogenesis of SARS. © 2007 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio

Differentiating Embryonic Stem Cells Pass through ‘Temporal Windows’ That Mark Responsiveness to Exogenous and Paracrine Mesendoderm Inducing Signals

BACKGROUND: Mesendoderm induction during embryonic stem cell (ESC) differentiation in vitro is stimulated by the Transforming Growth Factor and Wingless (Wnt) families of growth factors. PRINCIPAL FINDINGS: We identified the periods during which Bone Morphogenetic Protein (BMP) 4, Wnt3a or Activin A were able to induce expression of the mesendoderm marker, Mixl1, in differentiating mouse ESCs. BMP4 and Wnt3a were required between differentiation day (d) 1.5 and 3 to most effectively induce Mixl1, whilst Activin A induced Mixl1 expression in ESC when added between d2 and d4, indicating a subtle difference in the requirement for Activin receptor signalling in this process. Stimulation of ESCs with these factors at earlier or later times resulted in little Mixl1 induction, suggesting that the differentiating ESCs passed through 'temporal windows' in which they sequentially gained and lost competence to respond to each growth factor. Inhibition of either Activin or Wnt signalling blocked Mixl1 induction by any of the three mesendoderm-inducing factors. Mixing experiments in which chimeric EBs were formed between growth factor-treated and untreated ESCs revealed that BMP, Activin and Wnt signalling all contributed to the propagation of paracrine mesendoderm inducing signals between adjacent cells. Finally, we demonstrated that the differentiating cells passed through 'exit gates' after which point they were no longer dependent on signalling from inducing molecules for Mixl1 expression. CONCLUSIONS: These studies suggest that differentiating ESCs are directed by an interconnected network of growth factors similar to those present in early embryos and that the timing of growth factor activity is critical for mesendoderm induction

Ror2 Enhances Polarity and Directional Migration of Primordial Germ Cells

The trafficking of primordial germ cells (PGCs) across multiple embryonic structures to the nascent gonads ensures the transmission of genetic information to the next generation through the gametes, yet our understanding of the mechanisms underlying PGC migration remains incomplete. Here we identify a role for the receptor tyrosine kinase-like protein Ror2 in PGC development. In a Ror2 mouse mutant we isolated in a genetic screen, PGC migration and survival are dysregulated, resulting in a diminished number of PGCs in the embryonic gonad. A similar phenotype in Wnt5a mutants suggests that Wnt5a acts as a ligand to Ror2 in PGCs, although we do not find evidence that WNT5A functions as a PGC chemoattractant. We show that cultured PGCs undergo polarization, elongation, and reorientation in response to the chemotactic factor SCF (secreted KitL), whereas Ror2 PGCs are deficient in these SCF-induced responses. In the embryo, migratory PGCs exhibit a similar elongated geometry, whereas their counterparts in Ror2 mutants are round. The protein distribution of ROR2 within PGCs is asymmetric, both in vitro and in vivo; however, this asymmetry is lost in Ror2 mutants. Together these results indicate that Ror2 acts autonomously to permit the polarized response of PGCs to KitL. We propose a model by which Wnt5a potentiates PGC chemotaxis toward secreted KitL by redistribution of Ror2 within the cell