Are food exposures obtained through commercial market panels representative of the general population? Implications for outbreak investigations

Current methods of control recruitment for case-control studies can be slow (a particular issue for outbreak investigations), resource-intensive and subject to a range of biases. Commercial market panels are a potential source of rapidly recruited controls. Our study evaluated food exposure data from these panel controls, compared with an established reference dataset. Market panel data were collected from two companies using retrospective internet-based surveys; these were compared with reference data from the National Diet and Nutrition Survey (NDNS). We used logistic regression to calculate adjusted odds ratios to compare exposure to each of the 71 food items between the market panel and NDNS participants. We compared 2103 panel controls with 2696 reference participants. Adjusted for socio-demographic factors, exposure to 90% of foods was statistically different between both panels and the reference data. However, these differences were likely to be of limited practical importance for 89% of Panel A foods and 79% of Panel B foods. Market panel food exposures were comparable with reference data for common food exposures but more likely to be different for uncommon exposures. This approach should be considered for outbreak investigation, in conjunction with other considerations such as population at risk, timeliness of response and study resources

Glutathione – linking cell proliferation to oxidative stress

Significance: The multifaceted functions of reduced glutathione (gamma-glutamyl-cysteinyl-glycine; GSH) continue to fascinate plants and animal scientists, not least because of the dynamic relationships between GSH and reactive oxygen species (ROS) that underpin reduction/oxidation (redox) regulation and signalling. Here we consider the respective roles of ROS and GSH in the regulation of plant growth, with a particular focus on regulation of the plant cell cycle. Glutathione is discussed not only as a crucial low molecular weight redox buffer that shields nuclear processes against oxidative challenge but also a flexible regulator of genetic and epigenetic functions. Recent Advances: The intracellular compartmentalization of GSH during the cell cycle is remarkably consistent in plants and animals. Moreover, measurements of in vivo glutathione redox potentials reveal that the cellular environment is much more reducing than predicted from GSH/GSSG ratios measured in tissue extracts. The redox potential of the cytosol and nuclei of non-dividing plant cells is about -300 mV. This relatively low redox potential is maintained even in cells experiencing oxidative stress by a number of mechanisms including vacuolar sequestration of GSSG. We propose that regulated ROS production linked to glutathione-mediated signalling events are the hallmark of viable cells within a changing and challenging environment. Critical Issues: The concept that the cell cycle in animals is subject to redox controls is well established but little is known about how ROS and GSH regulate this process in plants. However, it is increasingly likely that similar redox controls exist in plants, although possibly through different pathways. Moreover, redox-regulated proteins that function in cell cycle checkpoints remain to be identified in plants. While GSH-responsive genes have now been identified, the mechanisms that mediate and regulate protein glutathionylation in plants remain poorly defined. Future Directions: The nuclear GSH pool provides an appropriate redox environment for essential nuclear functions. Future work will function on how this essential thiol interacts with the nuclear thioredoxin system and nitric oxide to regulate genetic and epigenetic mechanisms. The characterization of redox-regulated cell cycle proteins in plants, and the elucidation of mechanisms that facilitate GSH accumulation in the nucleus are keep steps to unravelling the complexities of nuclear redox controls

Learning to breathe: developmental phase transitions in oxygen status

Plants are developmentally disposed to considerable changes in oxygen availability, yet our understanding of the importance of hypoxia is almost entirely limited to stress biology. Differential patterns of the abundance of oxygen, nitric oxide (.NO) and reactive oxygen species (ROS), and redox potential occur in organs and meristems, and examples are emerging in the literature of mechanistic relationships of these to development. Here, we describe the convergence of these cues in meristematic and reproductive tissues, and discuss the evidence for regulated hypoxic niches, within which oxygen-, ROS-, .NO- and redox-dependent signalling curate developmental transitions in plants

Effectiveness of common household cleaning agents in reducing the viability of human influenza A/H1N1

In the event of an influenza pandemic, the majority of people infected will be nursed at home. It is therefore important to determine simple methods for limiting the spread of the virus within the home. The purpose of this work was to test a representative range of common household cleaning agents for their effectiveness at killing or reducing the viability of influenza A virus

Monitoring of RAS mutant clones in plasma of patients with RAS mutant metastatic colorectal cancer

Circulating tumor DNA; Liquid biopsy; Metastatic colorectal cancerADN tumoral circulante; Biopsia liquida; Cáncer colorrectal metastásicoADN tumoral circulant; Biòpsia líquida; Càncer colorectal metastàticPurpose Some patients with histologically confirmed primary mCRC and mutated RAS reported undetectable RAS mutant clones in plasma after receiving anti-VEGF treatment. The aim was to prospectively assess it with its potential therapeutic implications. Methods RAS mutant genes in solid biopsy (before first-line treatment: FOLFOX/CAPOX + bevacizumab) were compared in liquid biopsy (before second-line treatment: panitumumab + FOLFIRI), using Idylla™ system. Discordant results between solid/liquid biopsies were assessed by the next-generation sequencing (NGS) test (solid/liquid biopsies). Results Twenty-three patients were assessed (seven had RAS mutant discrepancies between solid/liquid biopsies). The NGS test confirmed that 3/23 (13%) patients had undetectable RAS mutant clones in liquid biopsy and 3/23 (13%) presented discrepancies in solid biopsy (Idylla™ system vs. NGS test). Conclusion Thirteen percentage of patients had undetectable RAS mutant clones in liquid biopsy after first-line treatment. However, some discrepancies between solid and liquid biopsies have been observed. These results suggest a need to improve accuracy of RAS analyses, especially in solid biopsies.This work was supported by Amgen S.A. Amgen did not have any role in study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication

Prospective cohort study to investigate the burden and transmission of acute gastroenteritis in care homes: a study protocol.

INTRODUCTION: Noroviruses are the leading cause of acute gastroenteritis in all age groups, but illness is more severe and causes excess mortality in the elderly, particularly those in long-term care. The total burden of norovirus disease in the elderly in the UK is poorly defined; no current surveillance programmes systematically or accurately quantify norovirus infection in those living in care homes. The aim of this study is to evaluate an enhanced surveillance system for acute gastroenteritis among the elderly in care homes. METHODS AND ANALYSIS: We will conduct this prospective cohort study in care homes in North West England; residents and staff at study care homes will be asked to participate. We will prospectively enrol a cohort of participants in an enhanced surveillance system to capture the incidence of acute gastroenteritis and use multiplex PCR to detect pathogens. We will sample symptomatic and non-symptomatic participants to understand characteristics of norovirus disease and susceptibility to infection. We will generate novel data on transmission dynamics by collecting data on the pattern of interactions within care homes using electronic proximity sensors. Comparisons of outbreak and non-outbreak periods will be used to quantify the impact of norovirus outbreaks on care homes. ETHICS AND DISSEMINATION: The study has been approved by the North West-Greater Manchester South NHS Research Ethics Committee (REC Reference: 16/NW/0541). Study outputs will be disseminated through scientific conferences and peer-reviewed publications. This study will provide detailed insight on the burden and aetiology of acute gastroenteritis in care homes, in addition to generating novel data on transmission dynamics and risks. The study will identify areas for improving infection control practice and allow more accurate modelling of the introduction of interventions such as vaccination

Immune-related gene expression profiling after PD-1 blockade in non–small cell lung carcinoma, head and neck squamous cell carcinoma, and melanoma

Antibody targeting of the immune checkpoint receptor PD1 produces therapeutic activity in a variety of solid tumors, but most patients exhibit partial or complete resistance to treatment for reasons that are unclear. In this study, we evaluated tumor specimens from 65 patients with melanoma, lung nonsquamous, squamous cell lung or head and neck cancers who were treated with the approved PD1-targeting antibodies pembrolizumab or nivolumab. Tumor RNA before anti-PD1 therapy was analyzed on the nCounter system using the PanCancer 730-Immune Panel, and we identified 23 immune-related genes or signatures linked to response and progression-free survival (PFS). In addition, we evaluated intra- and interbiopsy variability of PD1, PD-L1, CD8A, and CD4 mRNAs and their relationship with tumor-infiltrating lymphocytes (TIL) and PD-L1 IHC expression. Among the biomarkers examined, PD1 gene expression along with 12 signatures tracking CD8 and CD4 T-cell activation, natural killer cells, and IFN activation associated significantly with nonprogressive disease and PFS. These associations were independent of sample timing, drug used, or cancer type. TIL correlated moderately (~0.50) with PD1 and CD8A mRNA levels and weakly (~0.35) with CD4 and PD-L1. IHC expression of PD-L1 correlated strongly with PD-L1 (0.90), moderately with CD4 and CD8A, and weakly with PD1. Reproducibility of gene expression in intra- and interbiopsy specimens was very high (total SD <3%). Overall, our results support the hypothesis that identification of a preexisting and stable adaptive immune response as defined by mRNA expression pattern is reproducible and sufficient to predict clinical outcome, regardless of the type of cancer or the PD1 therapeutic antibody administered to patients

Usefulness of multiparametric computerized tomography findings in the differential diagnosis of stroke mimics of epileptic origin: A preliminary study

Objetivo: Tras la activación del código ictus, hasta un 30% de los pacientes presentan cuadros imitadores del ictus, siendo la epilepsia el más frecuente. Evaluamos la utilidad de la TC cerebral multiparamétrica para la diferenciación de los déficit de origen comicial versus vascular. Material y métodos: Estudio observacional retrospectivo con recogida prospectiva de datos. Se revisan imágenes de TC multiparamétrica de pacientes atendidos como código ictus durante un año que finalmente fueron diagnosticados de etiología comicial. Resultados: N = 11 (varones 36%, edad media 74,5 a˜nos). Tres pacientes presentaban focalidad neurológica derecha, 4 focalidad izquierda y 4 afasia aislada. El tiempo máximo desde el inicio de la clínica hasta la realización de la TC multiparamétrica fue de 8,16 h. La TC perfusión fue normal en 2 pacientes. Nueve pacientes mostraron alargamiento/acortamiento del tiempo al pico (Tmáx), siendo los mapas de flujo y volumen variables. El electroencefalograma se realizó con un tiempo máximo de evolución desde el inicio de la clínica de 47,6 h. Cuatro registros mostraron hallazgos compatibles con estatus epiléptico, 2 actividad epileptiforme focal y los 5 restantes lentificación poscrítica ipsolateral a las anomalías de la TC perfusión. Conclusión: El alargamiento del tiempo al pico en una distribución cortical multilobar en ausencia de oclusión de gran vaso y con respeto de ganglios de la base ha resultado el parámetro más sensible para la diferenciación de estas entidades en nuestra serie. Consideramos que la TC cerebral multiparamétrica es una herramienta rápida, disponible y útil para el diagnóstico diferencial de síntomas neurológicos deficitarios de inicio brusco debidos a etiología comicial que son atendidos como código ictus.Objective: Thirty percent of the patients for whom code stroke is activated have stroke mimics, the most common being epilepsy. Our purpose was to evaluate the usefulness of multiparametric CT for differentiating between seizure-related symptoms and vascular events. Material and methods: We conducted a retrospective observational study; data were gathered prospectively during one year. We studied multiparametric CT images of patients admitted following code stroke activation and finally diagnosed with epilepsy. Results: The study included a total of 11 patients; 36% were men and mean age was 74.5 years. Three patients had right hemisphere syndrome, 4 displayed left hemisphere syndrome, and the remaining 4 had isolated aphasia. Maximum time from symptom onset to multiparametric CT study was 8.16 hours. Perfusion CT results were normal in 2 patients. Nine patients showed longer or shorter times to peak (Tmax); cerebral blood volume (CBV) and cerebral blood flow (CBF) maps varied. EEG was performed a maximum of 47.6 hours after symptom onset. Four patients showed findings compatible with status epilepticus, 2 displayed focal epileptiform activity, and 5 showed post-ictal slowing ipsilateral to perfusion CT abnormalities. Conclusion: The most sensitive parameter for differentiating between stroke and epilepsy in our series was increased time to peak in multilobar cortical locations in the absence of largevessel occlusion and basal ganglia involvement. Multiparametric CT is a fast, readily available, and useful tool for the differential diagnosis of acute-onset neurological signs of epileptic originin patients initially attended after code stroke activatio

Influenza and pneumococcal vaccine uptake among nursing home residents in Nottingham, England: a postal questionnaire survey

<p>Abstract</p> <p>Background</p> <p>Previous studies have shown influenza vaccine uptake in UK nursing home residents to be low. Very little information exists regarding the uptake of pneumococcal vaccine in this population. The formulation of policies relating to the vaccination of residents has been proposed as a simple step that may help improve vaccine uptake in care homes.</p> <p>Methods</p> <p>A postal questionnaire was sent to matrons of all care homes with nursing within the Greater Nottingham area in January 2006. Non respondents were followed up with up to 3 phone calls.</p> <p>Results</p> <p>30% (16/53) of respondents reported having a policy addressing influenza vaccination and 15% (8/53) had a policy addressing pneumococcal vaccination. Seasonal influenza vaccine coverage in care homes with a vaccination policy was 87% compared with 84% in care homes without a policy (p = 0.47). The uptake of pneumococcal vaccination was found to be low, particularly in care homes with no vaccination policy. Coverage was 60% and 32% in care homes with and without a vaccination policy respectively (p = 0.06). This result was found to be statistically significant on multivariate analysis (p = 0.03, R = 0.46)</p> <p>Conclusion</p> <p>The uptake of influenza vaccine among care home residents in the Nottingham region is relatively high, although pneumococcal vaccine uptake is low. This study shows that there is an association between pneumococcal vaccine uptake and the existence of a vaccination policy in care homes, and highlights that few care homes have vaccination policies in place.</p

Early impact of rotavirus vaccination in a large paediatric hospital in the UK

The impact of routine rotavirus vaccination on community-acquired (CA) and healthcare-associated (HA) rotavirus gastroenteritis (RVGE) at a large paediatric hospital, UK, was investigated over a 13-year period. A total of 1644 hospitalized children aged 0-15 years tested positive for rotavirus between July 2002 and June 2015. Interrupted time-series analysis demonstrated that, post vaccine introduction (July 2013 to June 2015), CA- and HA-RVGE hospitalizations were 83% [95% confidence interval (CI): 72-90%) and 83% (95% CI: 66-92%] lower than expected, respectively. Rotavirus vaccination has rapidly reduced the hospital rotavirus disease burden among both CA- and HA-RVGE cases