Shaping a universally broad antibody response to influenza amidst a variable immunoglobulin landscape

Sarah F Andrews | Adrian B McDermott

https://ift.tt/2Ik6EPV

Influenza vaccines: ‘tailor-made’ or ‘one fits all’

Giulietta Saletti | Thomas Gerlach | Guus F Rimmelzwaan

https://ift.tt/2HYSL6l

Immune evasion of the CD1d/NKT cell axis

Randy R Brutkiewicz | Laura Yunes-Medina | Jianyun Liu

https://ift.tt/2HXvphm

Elective endoscopic clipping for the treatment of symptomatic diverticular disease: a potential for 'cure

Message

Symptomatic diverticular disease (DD) is a major worldwide healthcare burden, and diverticular bleeding is one of its most common manifestations. Endoscopic clipping of selected diverticula in the acute or early posthaemorrhage period has been reported as a haemostatic intervention, but the effect of elective clipping is not known.

We present the prospective series of elective endoscopic clipping with the aim of treating all visible diverticula in patients with previous bleeding, resulting in near-complete disappearance of DD.

This may have significant implications for the management of DD worldwide and warrants further prospective research.

In more detail

This was a prospective, single-centre study enrolling consecutive patients attending a specialist DD clinic at our institution, who had been previously hospitalised for lower GI bleeding due to DD (table 1). The procedures and follow-up colonoscopies were carried out from April 2015 to April 2017 at King's College Hospital, London, UK. Patients with other GI pathologies...

https://ift.tt/2jvvwpJ

Vedolizumab is associated with changes in innate rather than adaptive immunity in patients with inflammatory bowel disease

Objective

Vedolizumab, a monoclonal antibody directed against the integrin heterodimer α4β7, is approved for the treatment of Crohn's disease and ulcerative colitis. The efficacy of vedolizumab has been suggested to result from inhibition of intestinal T cell trafficking although human data to support this conclusion are scarce. We therefore performed a comprehensive analysis of vedolizumab-induced alterations in mucosal and systemic immunity in patients with inflammatory bowel disease (IBD), using anti-inflammatory therapy with the TNFα antibody infliximab as control.

Design

Immunophenotyping, immunohistochemistry, T cell receptor profiling and RNA sequencing were performed using blood and colonic biopsies from patients with IBD before and during treatment with vedolizumab (n=18) or, as control, the anti-TNFα antibody infliximab (n=20). Leucocyte trafficking in vivo was assessed using single photon emission computed tomography and endomicroscopy.

Results

Vedolizumab was not associated with alterations in the abundance or phenotype of lamina propria T cells and did not affect the mucosal T cell repertoire or leucocyte trafficking in vivo. Surprisingly, however, α4β7 antibody treatment was associated with substantial effects on innate immunity including changes in macrophage populations and pronounced alterations in the expression of molecules involved in microbial sensing, chemoattraction and regulation of the innate effector response. These effects were specific to vedolizumab, not observed in response to the TNFα antibody infliximab, and associated with inhibition of intestinal inflammation.

Conclusion

Our findings suggest that modulation of innate immunity contributes to the therapeutic efficacy of vedolizumab in IBD.

Trial registration number

NCT02694588

https://ift.tt/2FLW9PO

Deep learning Radiomics of shear wave elastography significantly improved diagnostic performance for assessing liver fibrosis in chronic hepatitis B: a prospective multicentre study

Objective

We aimed to evaluate the performance of the newly developed deep learning Radiomics of elastography (DLRE) for assessing liver fibrosis stages. DLRE adopts the radiomic strategy for quantitative analysis of the heterogeneity in two-dimensional shear wave elastography (2D-SWE) images.

Design

A prospective multicentre study was conducted to assess its accuracy in patients with chronic hepatitis B, in comparison with 2D-SWE, aspartate transaminase-to-platelet ratio index and fibrosis index based on four factors, by using liver biopsy as the reference standard. Its accuracy and robustness were also investigated by applying different number of acquisitions and different training cohorts, respectively. Data of 654 potentially eligible patients were prospectively enrolled from 12 hospitals, and finally 398 patients with 1990 images were included. Analysis of receiver operating characteristic (ROC) curves was performed to calculate the optimal area under the ROC curve (AUC) for cirrhosis (F4), advanced fibrosis (≥F3) and significance fibrosis (≥F2).

Results

AUCs of DLRE were 0.97 for F4 (95% CI 0.94 to 0.99), 0.98 for ≥F3 (95% CI 0.96 to 1.00) and 0.85 (95% CI 0.81 to 0.89) for ≥F2, which were significantly better than other methods except 2D-SWE in ≥F2. Its diagnostic accuracy improved as more images (especially ≥3 images) were acquired from each individual. No significant variation of the performance was found if different training cohorts were applied.

Conclusion

DLRE shows the best overall performance in predicting liver fibrosis stages compared with 2D-SWE and biomarkers. It is valuable and practical for the non-invasive accurate diagnosis of liver fibrosis stages in HBV-infected patients.

Trial registration number

NCT02313649; Post-results.

https://ift.tt/2KDQY8r

Early application of haemostatic powder added to standard management for oesophagogastric variceal bleeding: a randomised trial

Background

Acute variceal bleeding (AVB) requires early therapeutic management by experienced endoscopists that often poses logistical challenges for hospitals. We assessed a different management concept with early application of haemostatic powder—which does not require high endoscopic expertise—added to conventional management in a randomised trial.

Methods

Cirrhotic patients with AVB received standard medical therapy and were randomised to either immediate endoscopy with haemostatic powder application within 2 hours of admission, followed by early elective endoscopy on the next day, that is, within 12–24 hours of admission for definitive treatment (study group) or to early elective endoscopy only (control group). In both groups, failures to achieve clinical haemostasis until the time of early elective endoscopy underwent rescue endoscopy with attempted conventional haemostasis. Primary outcome was endoscopic haemostasis at the elective endoscopy.

Results

Of 86 randomised patients with AVB, 5/43 in the study group required rescue endoscopy for failure of controlling spurting bleeding (n=4) after powder application or for early bleeding recurrence in one patient who died before repeating rescue endoscopy. In the control group, 13/43 patients required rescue endoscopic haemostasis for failure of clinical haemostasis (12%vs30%, p=0.034). In the remaining patients, early elective endoscopic haemostasis was achieved in all 38 patients in the study group, while all remaining 30 patients in the control group had fresh gastric blood or (10%) spurting bleeding at early elective endoscopy with successful haemostasis in all of them. Six-week survival was significantly improved in the study group (7%vs30%, p=0.006).

Conclusion

The new concept of immediate powder application improves early clinical and endoscopic haemostasis. This simplified endoscopic approach may have an impact on early and 6-week survival.

Trial registration number

NCT03061604 .

https://ift.tt/2FNGoI9

Efficacy of pharmacological therapies for the treatment of opioid-induced constipation: systematic review and network meta-analysis

Objective

Opioids are increasingly prescribed in the West and have deleterious GI consequences. Pharmacological therapies to treat opioid-induced constipation (OIC) are available, but their relative efficacy is unclear. We performed a systematic review and network meta-analysis to address this deficit in current knowledge.

Design

We searched MEDLINE, EMBASE, EMBASE Classic and the Cochrane central register of controlled trials through to December 2017 to identify randomised controlled trials (RCTs) of pharmacological therapies in the treatment of adults with OIC. Trials had to report a dichotomous assessment of overall response to therapy, and data were pooled using a random effects model. Efficacy and safety of pharmacological therapies was reported as a pooled relative risk (RR) with 95% CIs to summarise the effect of each comparison tested and ranked treatments according to their P-score.

Results

Twenty-seven eligible RCTs of pharmacological therapies, containing 9149 patients, were identified. In our primary analysis, using failure to achieve an average of ≥3 bowel movements (BMs) per week with an increase of ≥1 BM per week over baseline or an average of ≥3 BMs per week, to define non-response, the network meta-analysis ranked naloxone first in terms of efficacy (RR=0.65; 95% CI 0.52 to 0.80, P-score=0.84), and it was also the safest drug. When non-response to therapy was defined using failure to achieve an average of ≥3 BMs per week, with an increase of ≥1 BM per week over baseline, naldemedinewas ranked first (RR=0.66; 95% CI 0.56 to 0.77, P score=0.91) and alvimopan second (RR=0.74; 95% CI 0.57 to 0.94, P-score=0.71).

Conclusion

In network meta-analysis, naloxone and naldemedine appear to be the most efficacious treatments for OIC. Naloxone was the safest of these agents.

https://ift.tt/2KFHmKf

Directed evolution of the bacterial endo-β-1,4-glucanase from Streptomyces sp. G12 towards improved catalysts for lignocellulose conversion

With the aim to develop biocatalysts for enhanced hydrolysis of (hemi)cellulose into monosaccharides, random diversity by directed evolution was introduced in the gene coding for the endo-β-1,4-glucanase from Str...

https://ift.tt/2jyKuLO

The influence of oxygen and methane on nitrogen fixation in subarctic Sphagnum mosses

Biological nitrogen fixation is an important source of bioavailable nitrogen in Sphagnum dominated peatlands. Sphagnum mosses harbor a diverse microbiome including nitrogen-fixing and methane (CH4) oxidizing bact...

https://ift.tt/2HYMHdR

Effect of decanoic acid and 10-hydroxydecanoic acid on the biotransformation of methyl decanoate to sebacic acid

Biotransformation of fatty acid methyl esters to dicarboxylic acids has attracted much attention in recent years; however, reports of sebacic acid production using such biotransformation remain few. The toxici...

https://ift.tt/2rsUYRp

HIV-1 Tat alters neuronal intrinsic excitability

In HIV+ individuals, the virus enters the central nervous system and invades innate immune cells, producing important changes that result in neurological deficits. We aimed to determine whether HIV plays a dir...

https://ift.tt/2IcMjMi

Validity and reliability of the Utrecht Work Engagement Scale-Student Version in Sri Lanka

The present study was aimed at assessing the validity and the reliability of the Sinhala version of the Utrecht Work Engagement Scale-Student Version (UWES-S) among collegiate cycle students in Sri Lanka.

https://ift.tt/2JSakFJ

Intraportal Transplantation of Pancreatic Islets in Mouse Model

Pancreatic islet transplantation is a way to achieve normoglycemia in type 1 diabetes. This article focuses on the transplantation technique through the intraportal route to maintain normal glucose levels in diabetic mice.

https://ift.tt/2rmB767

A Drosophila In Vivo Injury Model for Studying Neuroregeneration in the Peripheral and Central Nervous System

Here, we present a protocol using the Drosophila sensory neuron - dendritic arborization (da) neuron injury model, which combines in vivo live imaging, two-photon laser axotomy/dendriotomy, and the powerful fly genetic toolbox, as a platform for screening potential promoters and inhibitors of neuroregeneration.

https://ift.tt/2roulvJ

Levator Auris Longus Preparation for Examination of Mammalian Neuromuscular Transmission Under Voltage Clamp Conditions

The protocol described in this paper uses the mouse levator auris longus (LAL) muscle to record spontaneous and nerve-evoked postsynaptic potentials (current-clamp) and currents (voltage-clamp) at the neuromuscular junction. Use of this technique can provide key insights into mechanisms of synaptic transmission under normal and disease conditions.

https://ift.tt/2KBKqqO

Retrospective MicroRNA Sequencing: Complementary DNA Library Preparation Protocol Using Formalin-fixed Paraffin-embedded RNA Specimens

Formalin-fixed paraffin-embedded specimens represent a valuable source of molecular biomarkers of human diseases. Here we present a laboratory-based cDNA library preparation protocol, initially designed with fresh frozen RNA, and optimized for the analysis of archived microRNAs from tissues stored up to 35 years.

https://ift.tt/2wdz8pN

Fetal Mouse Cardiovascular Imaging Using a High-frequency Ultrasound (30/45MHZ) System

High-frequency ultrasound imaging of the fetal mouse has improved imaging resolution and can provide precise non-invasive characterization of cardiac development and structural defects. The protocol outlined herein is designed to perform real-time fetal mice echocardiography in vivo.

https://ift.tt/2HVUAkv

Emergence of multidrug-resistant Providencia rettgeri isolates co-producing NDM-1 carbapenemase and PER-1 extended-spectrum β-lactamase causing a first outbreak in Korea

Nosocomial outbreak due to carbapenem-resistant Enterobacteriaceae has become serious challenge to patient treatment and infection control. We describe an outbreak due to a multidrug-resistant Providencia rettger...

https://ift.tt/2rm6IVD

Puerarin inhibits vascular smooth muscle cells proliferation induced by fine particulate matter via suppressing of the p38 MAPK signaling pathway

Fine particulate matter (PM2.5) is a major risk factor for the development and progression of atherosclerosis. Proliferation and infiltration of vascular smooth muscle cells (VSMCs) from the blood vessel media...

https://ift.tt/2wohTCj

Seminal Cell-Free DNA Assessment as a Novel Prostate Cancer Biomarker

Abstract

Cell-free DNA (cfDNA) includes circulating DNA fragments, which can be obtained from different human biological samples. cfDNA originates either from apoptotic and/or necrotic cells or is actively secreted by cancer cells. As yet, a quantification and size distribution assessment of seminal plasma cfDNA from prostate cancer patients has never been assessed. To discover a novel, sensitive, non-invasive biomarker of prostate cancer, through the fluorometric quantification and the electrophoretic analysis of seminal cfDNA in prostate cancer patients compared to healthy individuals. The concentration of seminal plasma cfDNA in prostate cancer patients was 2243.67 ± 1758 ng/μl, compared to 57.7 ± 4.8 ng/μl in healthy individuals (p < 0.05). Electrophoresis sites distribution patterns were different; ladder fragmentation was associated with prostate cancer patients and apoptotic electrophoretic fragmentation with healthy individuals. Human seminal fluid can be a valuable source of cfDNA in the setting of liquid biopsy procedures for the identification of novel oncological biomarkers. Seminal plasma cfDNA in prostate cancer patients is significantly more concentrated than that of age-matched, healthy controls. Fluorometric measurement and electrophoretic assessment allow a reliable quantification and characterization of seminal plasma cfDNA, which can be used routinely in prostate cancer screening programs.

https://ift.tt/2rmysIR

Paroxysmal ocular movements – an early sign in Glut1 deficiency Syndrome

Abstract

The authors describe a 3-year-old female, diagnosed with GLUT1 deficiency Syndrome, with a previously unreported mutation in exon 7 of the SLC2A1 gene: c.968_972 + 3del P. (Val323Alafs*53), characterized by a classic phenotypic of acquired microcephaly, developmental delay, ataxia, spasticity, and epilepsy. Ketogenic diet was started at the age of 30 months with epilepsy improvement. She presented paroxysmal ocular movements in the first 12 months of life, recently defined as "aberrant gaze saccades", that are present in the early phase of visual system development, being one of the first disease signs, but easily disregarded. Recognizing these particular ocular movements would allow an early diagnosis, followed by ketogenic diet implementation, improving significantly the prognosis and the neurological development of those children.

https://ift.tt/2HU5QSc

Effect of Selenium Nanoparticle Supplementation on Tissue Inflammation, Blood Cell Count, and IGF-1 Levels in Spinal Cord Injury-Induced Rats

Abstract

Selenium is known to be a neuroprotective agent in respect to a number of neuronal diseases and pain. The aim of this study was to evaluate the neuroprotective effect of the oral administration of selenium nanoparticles in rats with spinal cord injury (SCI). Forty adult female rats were randomly assigned to two equal groups as experimental and control. Under general inhalation anesthesia, in both groups, SCI was created, at the T9–10 level of the column. On the third day after the operation, a supplement of selenium nanoparticle was administered to the experimental group at 0.2 mg/kg per day. The histology of the site of injury, IGF-1 serum concentrations, and changes in the white blood cells were examined in both groups at different pre-surgical and post-surgical times. The results of the current study showed a significant decrease in the total white blood cells, including lymphocyte, neutrophil, and monocyte in the experimental group compared to the control group. Histological evaluation showed that the inflammatory responses reduced significantly in the experimental group compared to the control group. In conclusion, we speculate that the decrease in the number of inflammatory cells after oral administration of the selenium nanoparticles is due to the neuroprotective effects of this nanoparticle.

https://ift.tt/2jv61ox

Antibiotic prescribing behavior among general practitioners – a questionnaire-based study in Germany

This study investigates the barriers and facilitators of the use of antibiotics in acute respiratory tract infections by general practitioners (GPs) in Germany.

https://ift.tt/2jxs6Da

Risk of ischemic heart disease after radiotherapy for ductal carcinoma in situ

Abstract

Purpose

The use of adjuvant radiotherapy (RT) in the management of ductal carcinoma in situ (DCIS) is increasing. Left-sided breast irradiation may involve exposure of the heart to ionising radiation, increasing the risk of ischemic heart disease (IHD). We examined the incidence of IHD in a population-based cohort of women with DCIS.

Methods

The Breast Cancer DataBase Sweden (BCBase) cohort includes women registered with invasive and in situ breast cancers 1992–2012 and age-matched women without a history of breast cancer. In this analysis, 6270 women with DCIS and a comparison cohort of 31,257 women were included. Through linkage with population-based registers, data on comorbidity, socioeconomic status and incidence of IHD was obtained. Hazard ratios (HR) for IHD with 95% confidence intervals (CI) were analysed.

Results

Median follow-up time was 8.8 years. The risk of IHD was not increased for women with DCIS versus women in the comparison cohort (HR 0.93; 95% CI 0.82–1.06), after treatment with radiotherapy versus surgery alone (HR 0.77; 95% CI 0.60–0.98) or when analysing RT by laterality (HR 0.85; 95% CI 0.53–1.37 for left-sided versus right-sided RT).

Conclusions

The risk of IHD was lower for women with DCIS allocated to RT compared to non-irradiated women and to the comparison cohort, probably due to patient selection. Comparison of RT by laterality did not show any over-risk for irradiation of the left breast.

https://ift.tt/2JUjAZO

Association of Parkinson’s disease with industry sectors: a French nationwide incidence study

Abstract

In order to identify working environments at risk for Parkinson's disease (PD), we investigated the relation between the importance of industry sectors, used as a surrogate for occupational exposures, and PD incidence in French cantons. The number of incident PD cases (2010–2014) in 3689 cantons of metropolitan France was determined using drug claims from French National Health Insurance databases. The proportions of workers in 38 industry sectors in 2006 were calculated for each canton. Associations between the proportions of workers in industry sectors and PD age/sex-standardized incidence ratios were examined using incidence rate ratios (IRR) and 95% confidence intervals (CI) estimated with multilevel negative binomial regressions with a random intercept at the canton-level and adjusted for smoking, deprivation index, and density of neurologists. We then used two-step semi-Bayes hierarchical regression (HR) to include prior information about exposure to pesticides, metals, and solvents in each industry sector. We identified 112,625 incident cases. PD incidence was higher in areas characterized by high proportions of workers in "Agriculture, forestry and fishing" (IRR_HR = 1.042; CI 95% = 1.014–1.070; p-Trend_HR = 0.004), "Manufacture of textiles, wearing apparel, leather and related products" (IRR_HR = 1.024; CI 95% = 1.005–1.044; p-Trend_HR = 0.010), and "Manufacture of basic metals and fabricated metal products, except machinery and equipment" (IRR_HR = 1.024; CI 95% = 1.003–1.046; p-Trend_HR = 0.071). This nationwide study, based on a comprehensive analysis of industry sectors, shows significant associations between high proportions of workers in specific industry sectors (agriculture, metallurgy, textile) and PD incidence that may be targeted in further epidemiological studies to replicate and better understand these associations.

https://ift.tt/2HVEcAu

The heart of the matter: years-saved from cardiovascular and cancer deaths in an elite athlete cohort with over a century of follow-up

Abstract

To quantify the years of life saved from cardiovascular (CVD), cancer and overall deaths among elite athletes according to their main type of physiological effort performed in the Olympic Games. All French athletes participating in the Games from 1912 to 2012, with vital status validated and cause of death (if concerned) identified by the national registries were included (n = 2814, 455 died) and classified according to 6 groups of effort: POWER (continuous effort < 45 s); INTERMEDIATE (45 s ≤ continuous effort < 600 s); ENDURANCE (continuous effort ≥ 600 s); POLYVALENT (participating in different events entering different classifications), INTERMITTENT (intermittent effort, i.e. team sports); PRECISION (targeting events). The theoretical years-lost method was adapted to calculate gains in longevity (years-saved) according to specific-risks under the competing risks model and was implemented in R software. Considering overall-deaths, all groups significantly saved, on average, 6.5 years of life (95% CI 5.8–7.2) compared to the general population. This longevity advantage is mainly driven by a lower risk of cancer which, isolated, contributed to significantly save 2.3 years of life (95% CI 1.2–1.9) on average in each group. The risk of CVD-related mortality in the ENDURANCE and PRECISION groups is not significantly different from the general population. The other groups significantly saved, on average, 1.6 years of life (95% CI 1.2–1.9) from CVD death. The longevity benefits in elite athletes are associated with the type of effort performed during their career, mainly due to differences on the CVD-risk of death.

https://ift.tt/2HQvFTj

Cohort profile: The MULTI sTUdy Diabetes rEsearch (MULTITUDE) consortium

Purpose

Globally, the age-standardised prevalence of type 2 diabetes mellitus (T2DM) has nearly doubled from 1980 to 2014, rising from 4.7% to 8.5% with an estimated 422 million adults living with the chronic disease. The MULTI sTUdy Diabetes rEsearch (MULTITUDE) consortium was recently established to harmonise data from 17 independent cohort studies and clinical trials and to facilitate a better understanding of the determinants, risk factors and outcomes associated with T2DM.

Participants

Participants range in age from 3 to 88 years at baseline, including both individuals with and without T2DM. MULTITUDE is an individual-level pooled database of demographics, comorbidities, relevant medications, clinical laboratory values, cardiac health measures, and T2DM-associated events and outcomes across 45 US states and the District of Columbia.

Findings to date

Among the 135 156 ongoing participants included in the consortium, almost 25% (33 421) were diagnosed with T2DM at baseline. The average age of the participants was 54.3, while the average age of participants with diabetes was 64.2. Men (55.3%) and women (44.6%) were almost equally represented across the consortium. Non-whites accounted for 31.6% of the total participants and 40% of those diagnosed with T2DM. Fewer individuals with diabetes reported being regular smokers than their non-diabetic counterparts (40.3% vs 47.4%). Over 85% of those with diabetes were reported as either overweight or obese at baseline, compared with 60.7% of those without T2DM. We observed differences in all-cause mortality, overall and by T2DM status, between cohorts.

Future plans

Given the wide variation in demographics and all-cause mortality in the cohorts, MULTITUDE consortium will be a unique resource for conducting research to determine: differences in the incidence and progression of T2DM; sequence of events or biomarkers prior to T2DM diagnosis; disease progression from T2DM to disease-related outcomes, complications and premature mortality; and to assess race/ethnicity differences in the above associations.

https://ift.tt/2rmG9zv

Correction: Associations of behavioural risk factors and health status with changes in physical capability over 10 years of follow-up: the MRC National Survey of Health and Development

Cooper R, Muniz-Terrera G, Kuh D. Associations of behavioural risk factors and health status with changes in physical capability over 10 years of follow-up: the MRC National Survey of Health and Development. BMJ Open 2016;6:e009962. doi: 10.1136/bmjopen-2015-009962

The first line of the methods reads:

'The NSHD is a socially stratified sample of 5362 singleton births (2547 males and 2815 females)'

however, this should have read:

'The NSHD is a socially stratified sample of 5362 singleton births (2815 males and 2547 females)'.

https://ift.tt/2whhCko

Photomodulation in the treatment of chronic pain in patients with temporomandibular disorder: protocol for cost-effectiveness analysis

Introduction

Epidemiological data show that the signs and symptoms of temporomandibular disorder (TMD) start becoming apparent from 6 years of age, and during adolescence these signs and symptoms are similar to those of adults. The present study aims to estimate the direct costs for treatment of chronic muscle pain with photobiomodulation therapy, occlusal splint and placebo in patients with TMD; to evaluate the effectiveness of photobiomodulation therapy and occlusal splint for treatment of muscle pain in patients with TMD; to analyse the cost-effectiveness of the two proposed treatments for pain; and to describe and compare the results of the analyses of these treatments.

Methods and analysis

This is a prospective trial of clinical and economic analyses that will include 135 patientswith TMD aged between 15 years and 25 years, randomly assigned to a treatment group: G1 (photobiomodulation), G2 (occlusal splint) and G3 (placebo). The analyses will be based on the cost of each treatment during the 12-month period. The outcome of the analysis of effectiveness will be pain, measured periodically by means of clinical examination of Research Diagnostic Criteria for Temporomandibular Disorders. The cost-effectiveness ratio will be calculated using, as end points, pain and the ratio of the differences in costs between the groups studied. The evaluation of the impact of the treatment on quality of life will be determined by applying the adapted EuroQol-5D.

Ethics and dissemination

This protocol has been ethically approved by the local medical ethical committee, protocol number 2.014.339. Results will be submitted to international peer-reviewed journals and presented at international conferences.

Trial registration number

NCT03096301.

https://ift.tt/2jxiesZ

Delirium as a predictor of mortality in US Medicare beneficiaries discharged from the emergency department: a national claims-level analysis up to 12 months

Background

Delirium is common among seniors discharged from the emergency department (ED) and associated with increased risk of mortality. Prior research has addressed mortality associated with seniors discharged from the ED with delirium, however has generally relied on data from one or a small number of institutions and at single time points.

Objectives

Analyse mortality rates among seniors discharged from the ED with delirium up to 12 months at the national level.

Design

Retrospective cohort study.

Setting

Analysed data from the Centers for Medicare & Medicaid Services limited data sets for 2012–2013.

Participants

Medicare fee-for-service beneficiaries aged 65 years or older discharged from the ED. We focused on new incident cases of delirium, patients with any prior claims for delirium, hospice claims or end-stage renal disease were excluded. Sample size included 26 245 delirium claims, and a randomly selected sample of 262 450 controls.

Outcome measures

Mortality within 12 months after discharge from the ED, excluding patients transferred or admitted as inpatients.

Results

Among all beneficiaries, 46 508 (16.1%) died within 12 months, of which 39 404 (15.0%) were in the non-delirium (ie, control group) and 7104 (27.1%) were in the delirium cohort, respectively. Mortality was strongest at 30 days with an adjusted HR of 4.82 (95% CI 4.60 to 5.04). Over time, delirium was consistently associated with increased mortality risk compared with controls up to 12 months (HR 2.07; 95% CI 2.01 to 2.13). Covariates that affected mortality included older age, comorbidity and presence of dementia.

Conclusions

Our results demonstrate delirium is a significant marker of mortality among seniors in the ED, and mortality risk is most salient in the first 3 months following an ED visit. Given the significant clinical and financial implications, there is a need to increase delirium screening and management within the ED to help identify and treat this potentially fatal condition.

https://ift.tt/2HUnXnj

Evaluation of the association between sleep duration and tooth loss among Korean adults: data from the Korean National Health and Nutrition Examination Survey (KNHANES 2012-2014)

Objectives

This study assessed the association between sleep duration and tooth loss using nationally representative data. In this study, a cross-sectional analysis was performed using multivariable logistic regression analysis models.

Setting

The present study analysed data from the Korean National Health and Nutrition Examination Survey between 2012 and 2014.

Participants

A total of 14 675 respondents over 19 years old without missing values were included in this study.

Exposure and primary outcome measures

Sleep duration and tooth loss.

Results

Participants with a sleep duration of 6–8 hours showed the lowest prevalence of diabetes mellitus, hypertension, metabolic syndrome, periodontitis and meeting the waist circumference criteria for metabolic syndrome. Adjusted OR and their 95% CI of male individuals with fewer than 25 natural teeth were 1.426 (1.113 to 1.827), 1.290 (1.074 to 1.548), 0.988 (0.853 to 1.145), 1 (reference), 1.058 (0.907 to 1.235) and 1.620 (1.287 to 2.038) for sleep duration of 4 hours or less, 5 hours, 6 hours, 7 hours, 8 hours and 9 hours or more, respectively (p<0.05), after adjustments for age, sex, smoking, drinking, walking, frequency of tooth brushing per day, body mass index and periodontitis.

Conclusions

Our findings showed the U-shaped association between sleep duration and tooth loss was suggested by multiple logistic regression analyses after adjusting for confounding factors. Moreover, subgroup analyses showed that short and long sleep duration were associated with greater tooth loss in participants without diabetes mellitus, those without hypertension and those without metabolic syndrome.

https://ift.tt/2rlne87

Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry: protocol for a prospective, observational nationwide cohort study

Introduction

Atrial fibrillation (AF) is a worldwide healthcare burden that is associated with the ageing population. Elderly patients with AF with multiple comorbidities usually present with a high risk of thromboembolism and bleeding. Limited prospective data are available from Asian cohorts on the epidemiology and complications of AF. The present prospective cohort study aims to explore contemporary antithrombotic strategies among the elderly Chinese population in the new era of non-vitamin K antagonist oral anticoagulants and to compare the clinical characteristics and outcomes between Chinese and European AF populations.

Methods and analysis

The Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry will recruit 5000 patients with AF over 65 years of age in China. AF-related risks, including stroke/systemic thromboembolism and bleeding outcomes, will be assessed. Medical history, risk factors, demographic information and management will be collected at baseline, and clinical events during 1 year follow-up will be recorded. Follow-up will be conducted for at least 1 year and then annually thereafter. As our registry has a common protocol to the European Society of Cardiology EURObservational Research Programme AF general registry programme, preplanned analyses comparing the clinical profiles and outcomes will be performed. The ChiOTEAF registry offers an opportunity to provide a better understanding of the clinical profiles and adverse outcomes of patients with AF in China and allow for comparisons with a contemporary European population.

Ethics and dissemination

Ethics approval was granted by the Central Medical Ethic Committee of Chinese PLA General Hospital (approval no S2014-065-01). The (inter)national research presentations, peer-reviewed publications and media coverage of the research will be sued for dissemination of the results.

https://ift.tt/2whh4ek

How does exercise dose affect patients with long-term osteoarthritis of the knee? A study protocol of a randomised controlled trial in Sweden and Norway: the SWENOR Study

Introduction

Osteoarthritis (OA) of the knee is characterised by knee pain, disability and degenerative changes, and places a burden on societies all over the world. Exercise therapy is an often-used modality, but there is little evidence of what type of exercise dose is the most effective, indicating a need for controlled studies of the effect of different dosages. Thus, the aim of the study described in this protocol is to evaluate the effects of high-dose versus low-dose medical exercise therapy (MET) in patients with knee OA.

Methods and analysis

This is a multicentre prospective randomised two-arm trial with blinded assessment and data analysis. We are planning to include 200 patients aged 45–85 years with symptomatic (pain and decreased functioning) and X-ray verified diagnosis of knee OA. Those eligible for participation will be randomly allocated to either high-dose (n=100) or low-dose (n=100) MET. All patients receive three supervised treatments each week for 12 weeks, giving a total of 36 MET sessions. The high-dose group exercises for 70–90 min compared with 20–30 min for the low-dose group. The high-dose group exercises for a longer time, and receives a greater number of exercises with more repetitions and sets. Background and outcome variables are recorded at inclusion, and outcome measures are collected after every sixth treatment, at the end of treatment, and at 6-month and 12-month follow-ups. Primary outcome is self-rated knee functioning and pain using the Knee Injury and Osteoarthritis Outcome Score (KOOS). The primary end point is at the end of treatment after 3 months, and secondary end points are at 6 months and 12 months after the end of treatment.

Ethics and dissemination

This project has been approved by the Regional Research Ethics Committees in Stockholm, Sweden, and in Norway. Our results will be submitted to peer-reviewed journals and presented at national and international conferences.

Trial registration number

NCT02024126; Pre-results.

https://ift.tt/2jvG8F9

Glycated haemoglobin A1c (HbA1c) for detection of diabetes mellitus and impaired fasting glucose in Malawi: a diagnostic accuracy study

Objectives

To examine the accuracy of glycated haemoglobin A_1c (HbA_1c) in detecting type 2 diabetes and impaired fasting glucose among adults living in Malawi.

Design

A diagnostic validation study of HbA_1c. Fasting plasma glucose (FPG) ≥7.0 mmol/L was the reference standard for type 2 diabetes, and FPG between 6.1 and 6.9 mmol/L as impaired fasting glucose.

Participants

3645 adults (of whom 63% were women) recruited from two demographic surveillance study sites in urban and rural Malawi. This analysis excluded those who had a previous diagnosis of diabetes or had history of taking diabetes medication.

Results

HbA_1c demonstrated excellent validity to detect FPG-defined diabetes, with an area under the receiver operating characteristic (AUROC) curve of 0.92 (95% CI 0.90 to 0.94). At HbA_1c ≥6.5% (140 mg/dL), sensitivity was 78.7% and specificity was 94.0%. Subgroup AUROCs ranged from 0.86 for participants with anaemia to 0.94 for participants in urban Malawi. There were clinical and metabolic differences between participants with true diabetes versus false positives when HbA_1c was ≥6.5% (140 mg/dL).

Conclusions

The findings from this study provide justification to use HbA_1c to detect type 2 diabetes. As HbA_1c testing is substantially less burdensome to patients than either FPG testing or oral glucose tolerance testing, it represents a useful option for expanding access to diabetes care in sub-Saharan Africa.

https://ift.tt/2HWoK7h

Study protocol for the G-SPIRIT trial: a randomised, placebo-controlled, double-blinded phase III trial of granulocyte colony-stimulating factor-mediated neuroprotection for acute spinal cord injury

Introduction

Granulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial.

Methods and analysis

The objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m²/dayx5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients).

Ethics and dissemination

The study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper.

Trial registration number

UMIN000018752.

https://ift.tt/2rsiC0n

Assessing health, quality of life and urogenital function in a sample of the Swedish general population: a cross-sectional study

Objective

Evaluate the urinary, bowel and sexual function as well as stress symptoms and depression in a sample of the Swedish population.

Design

A random sample of Swedish men and women in age groups from 30 to 89 years, a total of 3000 individuals, were contacted and after receiving informed consent, a questionnaire was sent.

Main outcome measures

Measures of urinary, bowel, sexual function and quality of life.

Results

The questionnaire was sent to 2094 individuals who gave informed consent. The questionnaire was answered by 1078 individuals. Quality of life, stress symptoms and depressed mood were relatively constant across age groups for both men and women. Urinary function differed significantly across gender and age groups, but bowel function was relatively unaffected by age. Overall bowel dysfunction was slightly more prevalent among women compared with men. For both men and women, the frequency of intercourse or other sexual activities decreased with age, whereas sexually associated distress increased by age in men, but decreased among women.

Conclusions

In a general population, the urinary function varied across age and sex. Overall bowel dysfunction was slightly more prevalent among women compared with men. Sexually associated distress increased by age for men, but decreased for women.

Trial registration number

NCT02392923; Results.

https://ift.tt/2HXXl4z

What is the epidemiology of medication errors, error-related adverse events and risk factors for errors in adults managed in community care contexts? A systematic review of the international literature

Objective

To investigate the epidemiology of medication errors and error-related adverse events in adults in primary care, ambulatory care and patients' homes.

Design

Systematic review.

Data source

Six international databases were searched for publications between 1 January 2006 and 31 December 2015.

Data extraction and analysis

Two researchers independently extracted data from eligible studies and assessed the quality of these using established instruments. Synthesis of data was informed by an appreciation of the medicines' management process and the conceptual framework from the International Classification for Patient Safety.

Results

60 studies met the inclusion criteria, of which 53 studies focused on medication errors, 3 on error-related adverse events and 4 on risk factors only. The prevalence of prescribing errors was reported in 46 studies: prevalence estimates ranged widely from 2% to 94%. Inappropriate prescribing was the most common type of error reported. Only one study reported the prevalence of monitoring errors, finding that incomplete therapeutic/safety laboratory-test monitoring occurred in 73% of patients. The incidence of preventable adverse drug events (ADEs) was estimated as 15/1000 person-years, the prevalence of drug–drug interaction-related adverse drug reactions as 7% and the prevalence of preventable ADE as 0.4%. A number of patient, healthcare professional and medication-related risk factors were identified, including the number of medications used by the patient, increased patient age, the number of comorbidities, use of anticoagulants, cases where more than one physician was involved in patients' care and care being provided by family physicians/general practitioners.

Conclusion

A very wide variation in the medication error and error-related adverse events rates is reported in the studies, this reflecting heterogeneity in the populations studied, study designs employed and outcomes evaluated. This review has identified important limitations and discrepancies in the methodologies used and gaps in the literature on the epidemiology and outcomes of medication errors in community settings.

https://ift.tt/2rme63p

Correction: Management of type 2 diabetes mellitus in people with severe mental illness: an online cross-sectional survey of healthcare professionals

McBain H, Lamontagne-Godwin F, Haddad M, et al. Management of type 2 diabetes mellitus in people with severe mental illness: an online cross-sectional survey of healthcare professionals. BMJ Open 2018;8:e019400. doi: 10.1136/bmjopen-2017-019400

This article has been corrected since it first published. The affiliation 'Community Health Newham, East London NHS Foundation Trust, London, UK' is now associated with author Kathleen Mulligan instead of Chris Flood.

https://ift.tt/2HWoJ3d

Role of sampling times and serum cortisol cut-off concentrations on the routine assessment of adrenal function using the standard cosyntropin test in an academic hospital from Spain: a retrospective chart review

Objectives

Aiming to validate the use of a single poststimulus sampling protocol for cosyntropin test short standard high-dose test (SST) in our institution, our primary objectives were (1) to determine the concordance between 30 and 60 min serum cortisol (SC) measurements during SST; and (2) to evaluate the diagnostic agreement between both sampling times when using classic or assay-specific and sex-specific SC cut-off values. The secondary objectives included (1) estimating the specificity and positive predictive value of 30 and 60 min sampling times while considering the suspected origin of adrenal insufficiency (AI); and (2) obtaining assay-specific cut-off values for SC after SST in a group of subjects with normal hypothalamic–pituitary–adrenal (HPA) axis.

Design and setting

This is a retrospective chart review study conducted at a Spanish academic hospital from 2011 to 2015.

Participants and interventions

Two groups were evaluated: (1) a main study group including 370 patients in whom SC was measured at 30 and 60 min during SST; and (2) a confirmative group that included 150 women presenting with a normal HPA axis in whom SST was conducted to rule out late-onset congenital adrenal hyperplasia. Diagnostic agreement between both sampling times was assessed by considering both classic (500 nmol/L) and assay-specific SC cut-off concentrations.

Results

Diagnostic agreement between both sampling times was greater when applying sex-specific and assay-specific cut-off values instead of the classic cut-off values. For suspected primary AI, 30 min SC determination was enough to establish a diagnosis in over 95% of cases, without missing any necessary treatment. When central AI is suspected, 60 min SC measurement was more specific, establishing a diagnosis in over 97% of cases.

Conclusions

Sex-specific and assay-specific SC cut-off values improve the diagnostic accuracy of SST. For primary disease, a subnormal SC response at 30 min is a reliable marker of adrenal dysfunction. On the contrary, when central AI is suspected, 60 min SC measurement improves the diagnostic accuracy of the test.

https://ift.tt/2jxiaJL

Methods and quality of disease models incorporating more than two sexually transmitted infections: a protocol for a systematic review of the evidence

Introduction

Disease models can be useful tools for policy makers to inform their decisions. They can help to estimate the costs and benefits of interventions without conducting clinical trials and help to extrapolate the findings of clinical trials to a population level.

Sexually transmitted infections (STIs) do not operate in isolation. Risk-taking behaviours and biological interactions can increase the likelihood of an individual being coinfected with more than one STI.

Currently, few STI models consider coinfection or the interaction between STIs. We aim to identify and summarise STI models for two or more STIs and describe their modelling approaches.

Methods and analysis

Six databases (Cochrane, Embase, PLOS, ProQuest, Medline and Web of Science) were searched on 27 November 2018 to identify studies that focus on the reporting of the methodology and quality of models for at least two different STIs. The quality of all eligible studies will be accessed using a percentage scale published by Kopec et al. We will summarise all used approaches to model two or more STIs in one model. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework will be used to report all outcomes.

Ethics and dissemination

Ethical approval is not required for this systematic review. The results of this review will be published in a peer-reviewed journal and presented at a suitable conference. The findings from this review will be used to inform the development of a new multi-STI model.

PROSPERO registration number

CRD42017076837.

https://ift.tt/2whROoe

What is the effect of prolonged sitting and physical activity on thoracic spine mobility? An observational study of young adults in a UK university setting

Objective

Sedentary behaviour has long been associated with neck and low back pain, although relatively little is known about the thoracic spine. Contributing around 33% of functional neck movement, understanding the effect of sedentary behaviour and physical activity on thoracic spinal mobility may guide clinical practice and inform research of novel interventions.

Design

An assessor-blinded prospective observational study designed and reported in accordance with Strengthening the Reporting of Observational Studies in Epidemiology.

Setting

UK university (June–September 2016).

Participants

A convenience sample (18–30 years) was recruited and based on self-report behaviours, the participants were assigned to one of three groups: group 1, sitters—sitting >7 hours/day+physical activity<150 min/week; group 2, physically active—moderate exercise >150 min/week+sitting <4 hours/day and group 3, low activity—sitting 2–7 hours/day+physical activity <150 min/week.

Outcome measures

Thoracic spine mobility was assessed in the heel-sit position using Acumar digital goniometer; a validated measure. Descriptive and inferential analyses included analysis of variance and analysis of covariance for between group differences and Spearman's rank correlation for post hoc analysis of associations.

Results

The sample (n=92) comprised: sitters n=30, physically active n=32 and low activity n=30. Groups were comparable with respect to age and body mass index.

Thoracic spine mobility (mean (SD)) was: group 1 sitters 64.75 (1.20), group 2 physically active 74.96 (1.18) and group 3 low activity 68.44 (1.22). Significant differences were detected between (1) sitters and low activity, (2) sitters and physically active (p<0.001). There was an overall effect size of 0.31. Correlations between thoracic rotation and exercise duration (r=0.67, p<0.001), sitting duration (r=–0.29, p<0.001) and days exercised (r=0.45, p<0.001) were observed.

Conclusions

Findings evidence reduced thoracic mobility in individuals who spend >7 hours/day sitting and <150 min/week of physical activity. Further research is required to explore possible causal relationships between activity behaviours and spinal musculoskeletal health.

https://ift.tt/2rjUc9e

Short-term abstinence from alcohol and changes in cardiovascular risk factors, liver function tests and cancer-related growth factors: a prospective observational study

Objective

To assess changes in metabolic risk factors and cancer-related growth factors associated with short-term abstinence from alcohol.

Design

Prospective, observational study.

Setting

Single tertiary centre.

Participants

Healthy subjects were recruited based on intention to: (1) abstain from alcohol for 1 month (abstinence group), or (2) continue to drink alcohol (control group). Inclusion criteria were baseline alcohol consumption >64 g/week (men) or >48 g/week (women). Exclusion criteria were known liver disease or alcohol dependence.

Primary and secondary outcome measures

The primary outcome was change in insulin resistance (homeostatic model assessment (HOMA) score). Secondary outcomes were changes in weight, blood pressure (BP), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and liver function tests. Primary and secondary outcomes were adjusted for changes in diet, exercise and cigarette smoking.

Results

The abstinence group comprised 94 participants (mean age 45.5 years, SD ±1.2) and the control group 47 participants (mean age 48.7 years, SD ±1.8). Baseline alcohol consumption in the abstinence group was 258.2 g/week, SD ±9.4, and in the control group 233.8 g, SD ±19.0. Significant reductions from baseline in the abstinence group (all p<0.001) were found in: HOMA score (–25.9%, IQR –48.6% to +0.3%), systolic BP (–6.6%, IQR –11.8% to 0.0%), diastolic BP (–6.3%, IQR –14.1% to +1.3%), weight (–1.5%, IQR –2.9% to –0.4%), VEGF (–41.8%, IQR –64.9% to –17.9%) and EGF (–73.9%, IQR –86.1% to –36.4%). None of these changes were associated with changes in diet, exercise or cigarette smoking. No significant changes from baseline in primary or secondary outcomes were noted in the control group.

Conclusion

These findings demonstrate that abstinence from alcohol in moderate–heavy drinkers improves insulin resistance, weight, BP and cancer-related growth factors. These data support an independent association of alcohol consumption with cancer risk, and suggest an increased risk of metabolic diseases such as type 2 diabetes and fatty liver disease.

https://ift.tt/2weXNKs

Predicting risk of hospitalisation: a retrospective population-based analysis in a paediatric population in Emilia-Romagna, Italy

Objectives

Develop predictive models for a paediatric population that provide information for paediatricians and health authorities to identify children at risk of hospitalisation for conditions that may be impacted through improved patient care.

Design

Retrospective healthcare utilisation analysis with multivariable logistic regression models.

Data

Demographic information linked with utilisation of health services in the years 2006–2014 was used to predict risk of hospitalisation or death in 2015 using a longitudinal administrative database of 527 458 children aged 1–13 years residing in the Regione Emilia-Romagna (RER), Italy, in 2014.

Outcome measures

Models designed to predict risk of hospitalisation or death in 2015 for problems that are potentially avoidable were developed and evaluated using the C-statistic, for calibration to assess performance across levels of predicted risk, and in terms of their sensitivity, specificity and positive predictive value.

Results

Of the 527 458 children residing in RER in 2014, 6391 children (1.21%) were hospitalised for selected conditions or died in 2015. 49 486 children (9.4%) of the population were classified in the 'At Higher Risk' group using a threshold of predicted risk >2.5%. The observed risk of hospitalisation (5%) for the 'At Higher Risk' group was more than four times higher than the overall population. We observed a C-statistic of 0.78 indicating good model performance. The model was well calibrated across categories of predicted risk.

Conclusions

It is feasible to develop a population-based model using a longitudinal administrative database that identifies the risk of hospitalisation for a paediatric population. The results of this model, along with profiles of children identified as high risk, are being provided to the paediatricians and other healthcare professionals providing care to this population to aid in planning for care management and interventions that may reduce their patients' likelihood of a preventable, high-cost hospitalisation.

https://ift.tt/2jtZgDA

Period of residence in prefabricated temporary housing and psychological distress after the Great East Japan Earthquake: a longitudinal study

Objectives

Previous studies have reported that displacement from one's own home after a natural disaster is associated with a higher degree of psychological distress. The present study investigated the longitudinal association between the period of residence in prefabricated temporary housing and psychological distress after the Great East Japan Earthquake.

Design, setting and participants

We conducted a longitudinal observation of 284 adults (aged ≥18 years) who had lived in prefabricated temporary housing in Miyagi, Northeastern Japan. The period of residence in prefabricated temporary housing was classified into three categories: <3, 3–4 and >4 years (ie, still living in prefabricated temporary housing).

Outcomes

The Kessler 6-item Psychological Distress Scale (K6) was assessed in both a baseline survey (2011) and a follow-up survey (2016). Higher psychological distress was defined by a K6 score of ≥5. We used Firth's penalised likelihood method in the multivariate logistic regression model to estimate the adjusted ORs and 95% CIs.

Results

Among the total participants, the proportion of individuals with higher psychological distress at the follow-up survey was significantly higher in the >4 years category (multivariate OR=4.00, 95% CI 1.67 to 10.16) than in the <3 years category. Among participants who had a lower degree of psychological distress at the baseline, the proportion of those whose psychological distress deteriorated was significantly higher in the >4 years category (multivariate OR=4.87, 95% CI 1.26 to 20.28) than in the <3 years category. On the other hand, among the participants who had a higher degree of psychological distress at the baseline, the proportion of those whose psychological distress ameliorated was significantly lower in the >4 years category (multivariate OR=0.26, 95% CI 0.06 to 0.85) than in the <3 years category.

Conclusions

The proportion of individuals with more severe psychological distress was higher among participants who had lived in prefabricated temporary housing for a long period.

https://ift.tt/2wgIUaF

An online randomized controlled trial, with or without problem-solving treatment, for long-term cancer survivors after hematopoietic cell transplantation

Abstract

Purpose

This randomized controlled trial examines the efficacy of INSPIRE, an INternet-based Survivorship Program with Information and REsources, with or without problem-solving treatment (PST) telehealth calls, for survivors after hematopoietic cell transplantation (HCT).

Methods

All adult survivors who met eligibility criteria were approached for consent. Participants completed patient-reported outcomes at baseline and 6 months. Those with baseline impaired scores on one or more of the outcomes were randomized to INSPIRE, INSPIRE + PST, or control with delayed INSPIRE access. Outcomes included Cancer and Treatment Distress, Symptom Checklist-90-R Depression, and Fatigue Symptom Inventory. Planned analyses compared arms for mean change in aggregated impaired outcomes and for proportion of participants improved on each outcome.

Results

Of 1306 eligible HCT recipients, 755 (58%) participated, and 344 (45%) had one or more impaired scores at baseline. We found no reduction in aggregated outcomes for either intervention (P > 0.3). In analyses of individual outcomes, participants randomized to INSPIRE + PST were more likely to improve in distress than controls (45 vs. 20%, RR 2.3, CI 1.0, 5.1); those randomized to INSPIRE alone were marginally more likely to improve in distress (40 vs. 20%, RR 2.0, CI 0.9, 4.5).

Conclusions

The INSPIRE online intervention demonstrated a marginal benefit for distress that improved with the addition of telehealth PST, particularly for those who viewed the website or were age 40 or older.

Implications for Cancer Survivors

Online and telehealth programs such as INSPIRE offer opportunities to enhance HCT survivorship outcomes, particularly for mood, though methods would benefit from strategies to improve efficacy.

https://ift.tt/2rmgeHv

Endoscopic self-expandable metal stent placement for malignant afferent loop obstruction caused by peritoneal recurrence after total gastrectomy

Abstract

Afferent loop obstruction (ALO) caused by cancer recurrence after total gastrectomy (TG) can be managed by either surgical or non-surgical treatment. The general condition of patients with recurrent gastric cancer is often poor, so a less invasive non-surgical treatment is desirable. We report the case of a 75-year-old male who had undergone TG for gastric cancer 6 months previously and who presented at our hospital with abdominal pain and vomiting. Abdominal computed tomography scan showed a dilated afferent loop, and additionally a low-density lesion around jejunojejunal anastomosis, suggesting that ALO is associated with peritoneal recurrence. A self-expandable metal stent (SEMS) was endoscopically placed to treat ALO after decompression of the dilated afferent loop using an intestinal tube. He retained a good quality of life until his death due to cancer progression 5 months after the SEMS placement. Our case indicates that SEMS could be a less invasive alternative to surgery, and may confer a better quality of life for patients with ALO due to cancer recurrence after TG. This is the valuable report of case in which endoscopic metallic stent placement succeeded for ALO caused by peritoneal recurrence after TG.

https://ift.tt/2KB9LkG

Round-robin test for the cell-of-origin classification of diffuse large B-cell lymphoma—a feasibility study using full slide staining

Abstract

Diffuse large B-cell lymphoma (DLBCL) is subdivided by gene expression analysis (GEP) into two molecular subtypes named germinal center B-cell-like (GCB) and activated B-cell-like (ABC) after their putative cell-of-origin (COO). Determination of the COO is considered mandatory in any new-diagnosed DLBCL, not otherwise specified according to the updated WHO classification. Despite the fact that pathologists are free to choose the method for COO classification, immunohistochemical (IHC) assays are most widely used. However, to the best of our knowledge, no round-robin test to evaluate the interlaboratory variability has been published so far. Eight hematopathology laboratories participated in an interlaboratory test for COO classification of 10 DLBCL tumors using the IHC classifier comprising the expression of CD10, BCL6, and MUM1 (so-called Hans classifier). The results were compared with GEP for COO signature and, in a subset, with results obtained by image analysis. In 7/10 cases (70%), at least seven laboratories assigned a given case to the same COO subtype (one center assessed one sample as not analyzable), which was in agreement with the COO subtype determined by GEP. The results in 3/10 cases (30%) revealed discrepancies between centers and/or between IHC and GEP subtype. Whereas the CD10 staining results were highly reproducible, staining for MUM1 was inconsistent in 50% and for BCL6 in 40% of cases. Image analysis of 16 slides stained for BCL6 (N = 8) and MUM1 (N = 8) of the two cases with the highest disagreement in COO classification were in line with the score of the pathologists in 14/16 stainings analyzed (87.5%). This study describes the first round-robin test for COO subtyping in DLBCL using IHC and demonstrates that COO classification using the Hans classifier yields consistent results among experienced hematopathologists, even when variable staining protocols are used. Data from this small feasibility study need to be validated in larger cohorts.

https://ift.tt/2wnGC9R

Impact of conjunctival autograft on pterygium treatment: evaluation of related symptoms and patients’ satisfaction after surgery

https://ift.tt/2JU1Cqk

Somatotype, the risk of hydroxychloroquine retinopathy, and safe daily dosing guidelines

https://ift.tt/2IaG6kb

Use of a novel extended blink test to evaluate the performance of two polyvinylpyrrolidone-containing, silicone hydrogel contact lenses

https://ift.tt/2JSxrQj

Optical coherence tomography retinal nerve fiber layer analysis in eyes with long axial lengths

https://ift.tt/2IeR3Bb

Incorporation of the technologist’s opinion for arbitration of discrepant assessments among radiologists at screening mammography

Abstract

Purpose

We determined whether the addition of the technologist's opinion may be helpful in deciding if discordant readings at blinded double reading should be recalled.

Methods

A consecutive series of 99,013 digital screening mammograms, obtained between July 2013 and January 2015, were included. All mammograms were first interpreted by a technologist and then double read in a blinded fashion by a team of 13 screening radiologists. All concordant and discordant positive readings among radiologists were recalled.

Results

Out of 3562 recalls, 998 women were recalled after a discordant reading. Of these women, 337 (33.8%) had a positive technologist assessment, of which 40 (11.9%) were diagnosed with breast cancer. Sixty women with a negative technologist assessment (60/661, 9.1%) were diagnosed with breast cancer (p = 0.16). Recall rate would have decreased with technologist arbitration (3.6% vs. 2.9%, p < 0.001). Cancer detection rate decreased with 8.5%, from 7.1/1000 screens to 6.5/1000 screens (p = 0.10). Among women with a positive technologist assessment, the probability of breast cancer was highest in case of suspicious microcalcifications and lowest for suspicious masses (30.4% (17/56) versus 7.0% (16/212), p < 0.001). Breast cancers were diagnosed in all groups of mammographic abnormalities, except in women with a suspicious asymmetry and a negative technologist assessment.

Conclusions

Assessment by a technologist does not provide a significant discriminating ability in case of a discordant radiologist reading and, taking into account the decrease in cancer detection rate, does not appear to be a suitable arbitration strategy for discordant recalls at blinded double reading.

https://ift.tt/2HRf69Y

Cancers, Vol. 10, Pages 133: Translation Control by p53

Cancers, Vol. 10, Pages 133: Translation Control by p53

Cancers doi: 10.3390/cancers10050133

Authors: Justina Kasteri Dibash Das Xuelin Zhong Leah Persaud Ashleigh Francis Hilal Muharam Moira Sauane

The translation of mRNAs plays a critical role in the regulation of gene expression and therefore, in the regulation of cell proliferation, differentiation and apoptosis. Unrestricted initiation of translation causes malignant transformation and plays a key role in the maintenance and progression of cancers. Translation initiation is regulated by the ternary complex and the eukaryotic initiation factor 4F (eIF4F) complex. The p53 tumor suppressor protein is the most well studied mammalian transcription factor that mediates a variety of anti-proliferative processes. Post-transcriptional mechanisms of gene expression in general and those of translation in particular play a major role in shaping the protein composition of the cell. The p53 protein regulates transcription and controls eIF4F, the ternary complex and the synthesis of ribosomal components, including the down-regulation of rRNA genes. In summary, the induction of p53 regulates protein synthesis and translational control to inhibit cell growth.

https://ift.tt/2FKDUuj

Cancers, Vol. 10, Pages 134: The Prevalence of CD146 Expression in Breast Cancer Subtypes and Its Relation to Outcome

Cancers, Vol. 10, Pages 134: The Prevalence of CD146 Expression in Breast Cancer Subtypes and Its Relation to Outcome

Cancers doi: 10.3390/cancers10050134

Authors: Ingeborg E. de Kruijff Anna M. Timmermans Michael A. den Bakker Anita M.A.C. Trapman-Jansen Renée Foekens Marion E. Meijer-Van Gelder Esther Oomen-de Hoop Marcel Smid Antoinette Hollestelle Carolien H.M. van Deurzen John A. Foekens John W.M. Martens Stefan Sleijfer

CD146, involved in epithelial-to-mesenchymal transition (EMT), might affect cancer aggressiveness. We here investigated the prevalence of CD146 expression in breast cancer subtypes, its relation to prognosis, the relation between CD146 and EMT and the outcome to tamoxifen. Primary breast cancer tissues from 1342 patients were available for this retrospective study and immunohistochemically stained for CD146. For survival analyses, pure prognosis was studied by only including lymph-node negative patients who did not receive (neo)adjuvant systemic treatment (n = 551). 11% of the tumors showed CD146 expression. CD146 expression was most prevalent in triple-negative cases (64%, p &lt; 0.001). In univariable analysis, CD146 expression was a prognostic factor for both metastasis-free survival (MFS) (p = 0.020) and overall survival (OS) (p = 0.037), but not in multivariable analysis (including age, tumor size, grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67). No correlation between CD146 and EMT nor difference in outcome to first-line tamoxifen was seen. In this large series, our data showed that CD146 is present in primary breast cancer and is a pure prognostic factor for MFS and OS in breast cancer patients. We did not see an association between CD146 expression and EMT nor on outcome to tamoxifen.

https://ift.tt/2roVYoz

Gene therapy knockdown of VEGFR2 in retinal endothelial cells to treat retinopathy

Abstract

Inhibition of vascular endothelial growth factor (VEGF) in retinopathy of prematurity (ROP) raises concerns for premature infants because VEGF is essential for retinovascular development as well as neuronal and glial health. This study tested the hypothesis that endothelial cell-specific knockdown of VEGF receptor 2 (VEGFR2), or downstream STAT3, would inhibit VEGF-induced retinopathy without delaying physiologic retinal vascular development. We developed an endothelial cell-specific lentiviral vector that delivered shRNAs to VEGFR2 or STAT3 and a green fluorescent protein reporter under control of the VE-cadherin promoter. The specificity and efficacy of the lentiviral vector-driven shRNAs were validated in vitro and in vivo. In the rat oxygen-induced retinopathy model highly representative of human ROP, the effects of endothelial cell knockdown of VEGFR2 or STAT3 were determined on intravitreal neovascularization (IVNV), physiologic retinal vascular development [assessed as area of peripheral avascular/total retina (AVA)], retinal structure, and retinal function. Targeted knockdown of VEGFR2 or STAT3 specifically in retinal endothelial cells by subretinal injection of lentiviral vectors into postnatal day 8 rat pup eyes efficiently inhibited IVNV, and knockdown of VEGFR2 also reduced AVA and increased retinal thickness without altering retinal function. Taken together, our results support specific knockdown of VEGFR2 in retinal endothelial cells as a novel therapeutic method to treat retinopathy.

https://ift.tt/2JXanQH

DNA methylation-based reclassification of olfactory neuroblastoma

Abstract

Olfactory neuroblastoma/esthesioneuroblastoma (ONB) is an uncommon neuroectodermal neoplasm thought to arise from the olfactory epithelium. Little is known about its molecular pathogenesis. For this study, a retrospective cohort of n = 66 tumor samples with the institutional diagnosis of ONB was analyzed by immunohistochemistry, genome-wide DNA methylation profiling, copy number analysis, and in a subset, next-generation panel sequencing of 560 tumor-associated genes. DNA methylation profiles were compared to those of relevant differential diagnoses of ONB. Unsupervised hierarchical clustering analysis of DNA methylation data revealed four subgroups among institutionally diagnosed ONB. The largest group (n = 42, 64%, Core ONB) presented with classical ONB histology and no overlap with other classes upon methylation profiling-based t-distributed stochastic neighbor embedding (t-SNE) analysis. A second DNA methylation group (n = 7, 11%) with CpG island methylator phenotype (CIMP) consisted of cases with strong expression of cytokeratin, no or scarce chromogranin A expression and IDH2 hotspot mutation in all cases. T-SNE analysis clustered these cases together with sinonasal carcinoma with IDH2 mutation. Four cases (6%) formed a small group characterized by an overall high level of DNA methylation, but without CIMP. The fourth group consisted of 13 cases that had heterogeneous DNA methylation profiles and strong cytokeratin expression in most cases. In t-SNE analysis, these cases mostly grouped among sinonasal adenocarcinoma, squamous cell carcinoma, and undifferentiated carcinoma. Copy number analysis indicated highly recurrent chromosomal changes among Core ONB with a high frequency of combined loss of chromosome 1–4, 8–10, and 12. NGS sequencing did not reveal highly recurrent mutations in ONB, with the only recurrently mutated genes being TP53 and DNMT3A. In conclusion, we demonstrate that institutionally diagnosed ONB are a heterogeneous group of tumors. Expression of cytokeratin, chromogranin A, the mutational status of IDH2 as well as DNA methylation patterns may greatly aid in the precise classification of ONB.

https://ift.tt/2rmz8Om

A Comparative Study of Iodized Salt Programs: Shanghai and Switzerland

Abstract

Both Shanghai and Switzerland are developed regions with long-standing salt iodization programs and periodic monitoring. However, the two regions have their own approach to the implementation of the iodized salt policy. In Shanghai, monitoring was carried out every few years, using probability-proportional-to-size sampling technique to select 30 sampling units. Each unit consisted of more than 12 pregnant women and one randomly selected primary school. Urine samples were then taken from the chosen pregnant women and randomly recruited students of that school for iodine test. Data of Switzerland used in this comparative study was extracted from published researches. In Shanghai, the median urinary iodine concentration (UIC) in 2014 was 20% lower than in 1999 (P < 0.05). The median UIC of pregnant women in 2014 was 9.5% lower than that in 2011 (P < 0.05). In terms of iodized salt concentration, opposite to the increasing in Switzerland, it has exhibited a downward trend in Shanghai (P < 0.05). For the years monitored, the iodized salt concentration in Shanghai was significantly (P < 0.05) higher than in Switzerland. Though the UIC of children exhibited a downward trend in Shanghai (P < 0.05), it was still significantly (P < 0.05) higher than in Switzerland over the same monitoring period. However, the UIC in pregnant women was a totally different story, which was significantly (P < 0.05) lower in Shanghai than in Switzerland. Iodized salt is very important for maintaining sufficient iodine level in the population. Appropriate concentration of iodine in fortified salt needs to be decided according to local conditions. Special attention should be paid to the iodine level of pregnant women in Shanghai, and more education about iodine is necessary for the public health.

https://ift.tt/2FLyE9J

Baseline health indicators of Eastern Pacific Green Turtles ( Chelonia mydas ) from Baja California Sur, Mexico

Abstract

Sea turtle health is an important component of conservation since these taxa is susceptible to infectious diseases that can cause illness leading to mortality. Threats to the health, survival, and reproduction of sea turtles are increasingly documented; however, prevention and control has not yet been successfully achieved. Thus, information about health indicators of sea turtles is a useful tool in order to achieve the best possible conservation measures. The objective of this study was to establish a baseline of health indicators of free-ranging Eastern Pacific green turtles (Chelonia mydas) from neritic foraging and juvenile developmental habitats in Baja California Sur. Here, we contribute baseline and reference interval values of vital signs, complete blood count, and plasma blood chemistry for live specimens from coastal lagoons: Ojo de liebre and San Ignacio in Baja California Sur, Mexico. With the integration of these indicators, 79 turtles were diagnosed as "healthy." Development of site-specific baseline of health indicators for free-ranging sea turtle populations allows to infer that the habitat provides adequate conditions for these species to carry out the activities corresponding to their stage of development and helps to create the management plans and pertinent conservation strategies as well as for the organisms in the area.

https://ift.tt/2jwXaTa

Anaerobic carbon monoxide metabolism by Pleomorphomonas carboxyditropha sp. nov., a new mesophilic hydrogenogenic carboxydotroph

Abstract

Carbon monoxide (CO)-metabolism and phenotypic and phylogenetic characterization of a novel anaerobic, mesophilic and hydrogenogenic carboxydotroph are reported. Strain SVCO-16 was isolated from anaerobic sludge and grows autotrophically and mixotrophically with CO. The genes cooS and cooF, coding for a CO dehydrogenase complex, and genes similar to hycE2, encoding a CO-induced hydrogenase, were present in its genome. The isolate produces H₂ and CO₂ from CO, and acetate and formate from organic substrates. Based on the 16S rRNA sequence, it is an Alphaproteobacterium most closely related to the genus Pleomorphomonas (98.9%–99.2% sequence identity). Comparison with other previously characterized Pleomorphomonas showed that P. diazotrophica and P. oryzae do not metabolize CO, and P. diazotrophica does not grow anaerobically with organic substrates. Average nucleotide identity values between strain SVCO-16 and P. diazotrophica, P. oryzae or P. koreensis were 86.66 ± 0.21%. These values are below the boundary to define species (95%–96%). Digital DNA-DNA hybridization estimates between strain SVCO-16 and reference strains were also below the 70% threshold for species delineation: 29.1%–34.5%. Based on the differences in CO metabolism, genome analyses and cellular fatty acid composition, the isolate should be classified into the genus Pleomorphomonas as a representative of a novel species, Pleomorphomonas carboxyditropha. The type strain of Pleomorphomonas carboxyditropha is SVCO-16^T (strain deposit numbers, DSM 106132^T and TSD-119^T).

https://ift.tt/2KFIPAu

Comparing rock-inhabiting microbial communities in different rock types from a high arctic polar desert

Abstract

Although rocks are habitable places for microbes in extreme environments, microbial diversity in these lithic environments is still poorly understood. The diversity and abundance of rock-inhabiting microbial communities in different types of rock in Svalbard, Norwegian High Arctic were examined using NGS sequencing of bacterial 16S rRNA genes and fungal 28S rRNA genes. Compositions of both bacterial and fungal communities varied across different rock types: sandstone, limestone, basalt, granite and travertine. Bacterial communities were dominated by Actinobacteria, Proteobacteria, Chloroflexi, Bacteroidetes and Acidobacteria. Fungal communities consisted of Eurotiomycetes, Lecanoromycetes, Dothideomycetes and Leotiomycetes. Both bacterial and fungal community compositions were significantly correlated with the geochemical characteristics of rocks. Bacterial communities were considerably correlated with the rock elements such as Mg and Ca. Fungal communities were considerably correlated with Fe. Interestingly, many dominant bacterial and fungal operational taxonomic units in the investigated rocks from the study area were closely affiliated to those found in other cold regions such as Alpine area, Arctic and Antarctica, suggesting that environmental constraints such as cold temperature may lead to convergence in microbial community composition. These results confirm that rocks in cold environments act as reservoirs of diverse bacteria and fungi, which may improve our understanding of lithic microbial ecology in the cold desert.

https://ift.tt/2rlj1kj

The sensory origin of the sense of effort is context-dependent

Abstract

The origin of the sense of effort has been debated for several decades and there is still no consensus among researchers regarding the underlying neural mechanisms. Some advocate that effort perception mainly arises from an efference copy originating within the brain while others believe that it is predominantly carried by muscle afferent signals. To move the debate forward, we here tested the hypothesis that there is not one but several senses of effort which depend on the way it is evaluated. For this purpose, we used two different psychophysical tests designed to test effort perception in elbow flexors. One was a bilateral isometric force-matching task in which subjects were asked to direct similar amounts of effort toward their two arms, while the other consisted of a unilateral voluntary isometric contraction in which subjects had to rate their perceived effort using a Borg scale. Throughout two distinct experiments, effort perception was evaluated before and following different tendon vibration protocols intended to differentially desensitize muscle spindles and Golgi tendon organs, and to affect the gain between the central effort and muscle contraction intensity. By putting all the results together, we found that spindle afferents played divergent roles across tasks. Namely, while they only acted as modulators of motor pathway excitability during the bilateral task, they clearly intervened as the predominant psychobiological signal of effort perception during the unilateral task. Therefore, the sensory origin of the sense of effort is not central or peripheral. Rather, it is context-dependent.

https://ift.tt/2IgwILy

Unilateral wrist extension training after stroke improves strength and neural plasticity in both arms

Abstract

Stroke induces bilateral neurological impairment and muscle weakness yielding neurologically more (MA; paretic) and less affected (LA; non-paretic) sides. "Cross-education" refers to training one side of the body to increase strength in the same muscles on the untrained side. Past work showed dorsiflexion training of the LA side produced bilateral strength increases after stroke. The current study explored the presence and extent of cross-education after arm strength training in chronic stroke. Twenty-four chronic stroke participants completed 5 weeks of maximal wrist extension training using their LA arm. Maximal voluntary contraction force, arm motor impairment and functional performance were measured before and after training. Both spinal cord plasticity (n = 12: reciprocal inhibition and cutaneous reflexes, University of Victoria) and cortical plasticity (n = 12: cortical silent period, short-interval intracortical inhibition, intracortical facilitation and transcallosal inhibition, University of British Columbia) were assessed. Five weeks after training, 20 participants completed a follow-up maximal wrist extension retention test. LA wrist extension force increased 42% and MA by 35%. Strength gains were maintained in the follow-up test. Clinically meaningful increases in Fugl-Meyer scores were noted in four participants. Muscle activation was correlated with cutaneous reflex amplitudes after training in the MA arm. LA cortical silent period and transcallosal inhibition from both hemispheres significantly decreased after training. This study shows that high-intensity training with the neurologically less affected "non-paretic" arm can improve strength bilaterally and alter both spinal and cortical plasticity. The extent to which this plasticity can be enhanced or functionally exploited remains to be examined.

https://ift.tt/2roEiJA

Prospective Assessment of Linox Implantable Cardioverter Defibrillator Leads for Structural or Electrical Abnormalities

Abstract

Introduction

Insulation failure leading to conductor externalization (CE) of a Linox (Biotronik, Berlin, Germany) implantable cardioverter defibrillator (ICD) lead has recently been reported. The aim of this study was to assess prospectively all Linox family ICD leads implanted at our center for evidence of CE or an electrical abnormality.

Methods

All patients with a Linox family ICD lead implanted at our center, between November 2007 and March 2015, were identified and all living patients were invited to attend for fluoroscopic screening and electrical assessment of the lead.

Results

A total of 183 patients had a Linox family ICD lead implanted at our center. Of these, 5 patients (2.7%) had the lead extracted because of electrical failure and 2 of these leads had evidence of CE. Out of 158 living patients with a Linox family ICD lead, 111 patients attended for screening (mean age 63.1 years, 22.5% female). In this group of patients, no cases of CE or electrical abnormalities of the lead were identified.

Conclusion

In this study evaluating 183 patients with a Linox family ICD lead implanted at a single center, 5 leads (2.7%) were explanted because of electrical failure and 2 of these leads had evidence of CE. Prospective fluoroscopic assessment of 111 Linox family ICD leads, with a mean dwell time of 31.5 months, revealed no further cases of CE.

https://ift.tt/2JUMFnU

Frailty in Hematologic Malignancy

Abstract

Purpose of Review

Older adults with hematologic malignancy are a growing demographic. Estimating risk of chemotherapy toxicity based on age alone is an unreliable estimate of quality of life, functional capacity, or risk of treatment complications.

Recent Findings

Dedicated geriatric assessment tools can aid the clinician in identifying geriatric syndromes such as frailty, resulting in improved prognostication to decrease morbidity and mortality. Frailty is not synonymous with individual performance status and is dynamic.

Summary

Establishing the patient goals, values, and preferences is central to the consideration of malignant hematology decision process. Careful considerations of available data on the patient's prognosis based on estimated life expectancy, geriatric assessment data, and age-specific cancer mortality, with and without treatment, can reconcile the risks and benefits. Assessments of frailty can aid the clinical feasibility and burden of the treatment to the patient and family in the context of each patient's unique needs.

https://ift.tt/2rsaXOP

Effect of high dietary levels of α-tocopherol acetate on immune response of light and heavy weight male broiler breeders

Abstract

The objective of this study was to investigate the effect of overdosing dietary α-tocopherol acetate (α-TOH) on immune response of heavy weight roosters. A total of 60 roosters (Ross 308) of light (LW, n = 30) and heavy weight (HW, n = 30) were kept in individual cages. Roosters were randomly allotted to ten treatment groups in a 2 × 5 factorial design. Each group received a basal diet supplemented with graded levels of α-TOH (0, 100, 200, 300, 400 mg/kg diet) for 10 weeks (from 25 to 35 week of age). Blood samples were collected at the fifth and tenth weeks of the experiment. Afterwards, humoral immune system function was evaluated by sheep red blood cell (SRBC) hemagglutination assay (HA) (at 35 weeks of age) and hemagglutination inhibition (HI) tests including antibody response to Newcastle disease viruses (NDV) and avian influenza viruses (AIV) (at 30 and 35 weeks of age). Cell-mediated immune response was evaluated by the cutaneous basophil hypersensitivity (CBH) test. A positive linear relationship was observed between incremental levels of dietary α-TOH and both humoral and cell-mediated immunity (P ≤ 0.05), with the highest immune parameters recorded for dietary supplementation of 400 mg/kg α-TOH (P ≤ 0.05). The results showed that CBH was significantly higher in LW roosters in comparison with HW roosters (P ≤ 0.05). However, the interaction of BW and α-TOH doses did not have any significant effect on immune responses (P ≥ 0.05). In conclusion, dietary supplementation of α-TOH at higher levels (four times more than the strain nutrients recommendation) had beneficial effects on the immune response of both HW and LW male broiler breeders.

https://ift.tt/2rlfqm8

Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Ann Oncol 2017; 28: iv22–iv40 (doi:10.1093/annonc/mdx224)

https://ift.tt/2FLskz0

Management of infusion reactions to systemic anticancer therapy: ESMO Clinical Practice Guidelines

Ann Oncol 2017; 28: iv100–iv118 (doi:10.1093/annonc/mdx216)

https://ift.tt/2KDqWlN

Activity and safety of crizotinib in patients with advanced clear-cell sarcoma with MET alterations: European Organization for Research and Treatment of Cancer phase II trial 90101 ‘CREATE’

Ann Oncol 2017; 28: 3000–3008 (doi: 10.1093/annonc/mdx527)

https://ift.tt/2FLv4MW

Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Ann Oncol 2017; 28: iv72–iv83 (doi:10.1093/annonc/mdx220)

https://ift.tt/2juJate

De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017

Ann Oncol 2017; 28: 1700–1712 (doi: 10.1093/annonc/mdx308)

https://ift.tt/2FMufDp

Pronounced maternal parent-of-origin bias for type-1 NF1 microdeletions

Abstract

Neurofibromatosis type 1 (NF1) is caused, in 4.7–11% of cases, by large deletions encompassing the NF1 gene and its flanking regions within 17q11.2. Different types of large NF1 deletion occur which are distinguishable by their breakpoint location and underlying mutational mechanism. Most common are the type-1 NF1 deletions of 1.4 Mb which exhibit recurrent breakpoints caused by nonallelic homologous recombination (NAHR), also termed unequal crossover. Here, we analyzed 37 unrelated families of patients with de novo type-1 NF1 deletions by means of short tandem repeat (STR) profiling to determine the parental origin of the deletions. We observed that 33 of the 37 type-1 deletions were of maternal origin (89.2% of cases; p < 0.0001). Analysis of the patients' siblings indicated that, in 14 informative cases, ten (71.4%) deletions resulted from interchromosomal unequal crossover during meiosis I. Our findings indicate a strong maternal parent-of-origin bias for type-1 NF1 deletions. A similarly pronounced maternal transmission bias has been reported for recurrent copy number variants (CNVs) within 16p11.2 associated with autism, but not so far for any other NAHR-mediated pathogenic CNVs. Region-specific genomic features are likely to be responsible for the maternal bias in the origin of both the 16p11.2 CNVs and type-1 NF1 deletions.

https://ift.tt/2ju993U