Impaired peripheral nerve regeneration in type-2 diabetic mouse model

Abstract

Peripheral neuropathy is one of the most common and serious complications of type-2 diabetes. Diabetic neuropathy is characterized by a distal symmetrical sensorimotor polyneuropathy, and its incidence increases in patients 40 years of age or older. In spite of extensive research over decades, there are few effective treatments for diabetic neuropathy besides glucose control and improved lifestyle. The earliest changes in diabetic neuropathy occur in sensory nerve fibers, with initial degeneration and regeneration resulting in pain. To seek its effective treatment, here we prepared a type-2 diabetic mouse model by giving mice 2 injections of streptozotocin and nicotinamide and examining the ability for nerve regeneration by using a sciatic nerve transection-regeneration model previously established by us. Seventeen weeks after the last injection, the mice exhibited symptoms of type-2 diabetes, i.e., impaired glucose tolerance, decreased insulin level, mechanical hyperalgesia, and impaired sensory nerve fibers in the plantar skin. These mice showed delayed functional recovery and nerve regeneration by 2 weeks compared with young healthy mice and by 1 week compared with age-matched non-diabetic mice after axotomy. Furthermore, type-2 diabetic mice displayed increased expression of PTEN in their DRG neurons. Administration of a PTEN inhibitor at the cutting site of the nerve for 4 weeks promoted the axonal transport and functional recovery remarkably. The present study demonstrates that peripheral nerve regeneration was impaired in type-2 diabetic model and that its combination with sciatic nerve transection is suitable for the study of the pathogenesis and treatment of early diabetic neuropathy.

This article is protected by copyright. All rights reserved.

http://ift.tt/2m7EJZA

The neural representation of social status in the extended face-processing network

Abstract

Social status is a salient cue that shapes our judgment and memory for other people and ultimately guides our social interactions. Despite the pervasive influence of status on social behavior, how information about the status of others is represented in the brain remains unclear. Here, we tested the hypothesis that social-status information is embedded in our neural representations of other individuals. Participants learned to associate faces with names, job titles that that varied in associated status, and explicit markers of reputational status (star ratings). Trained stimuli were presented in an fMRI experiment where participants performed a target detection task orthogonal to the variable of interest. A network of face-selective brain regions extending from the occipital lobe to the orbitofrontal cortex was localized and served as regions of interest. Using multivoxel pattern analysis, we found that face-selective voxels in the lateral orbitofrontal cortex – a region involved in social and nonsocial valuation, could decode faces based on their status. Similar effects were observed with two different status manipulations – one based on stored semantic knowledge (e.g. different careers) and one based on learned reputation (e.g. star ranking). These data suggest that a face-selective region of the lateral orbitofrontal cortex may contribute to the perception of social status, potentially underlying the preferential attention and favorable biases humans display toward high status individuals.

This article is protected by copyright. All rights reserved.

http://ift.tt/2yJj3Jl

Comparative Transcriptome Analysis Reveals Related Regulatory Mechanisms of Androgenic Gland in Eriocheir sinensis

Chinese mitten crab (Eriocheir sinensis) is one of the most commercially important aquaculture species in China. The androgenic gland (AG) of crustaceans plays pivotal roles in the regulation of male differentiation and in maintaining the male sexual characteristics. In order to reveal related mechanisms in AG, we compared transcriptomes of AG between proliferation and secretion phase. A total of 72,000 unigenes and 4,027 differentially expressed genes were obtained. Gene ontology enrichment analysis indicated that biological processes and metabolic pathways related to protein synthesis and secretion such as transcription, translation, and signal transduction were significantly enriched. Critical genes such as IAG, SXL, TRA-2, SRY, FTZ-F1, FOXL2, and FEM-1 were identified and potentially involved in maintaining the testis development and spermatogenesis. Ribosomes pathway revealed the cause of insulin-like androgenic gland hormone secretion increase. Three insulin-like receptors were thought to be associated with growth and spermatogenesis. In the neuroactive ligand-receptor interaction pathway, the expression of octopamine receptor, 5-HT receptor 1, and melatonin receptor was significantly changed, which revealed the key regulation mechanism of aggressive and mating behavior of males. Comparative transcriptome analysis provided new insights into the genome-wide molecular mechanisms of AG development and the regulatory mechanisms of male development.

http://ift.tt/2iGkAos

Multilevel Thresholding Method Based on Electromagnetism for Accurate Brain MRI Segmentation to Detect White Matter, Gray Matter, and CSF

This work explains an advanced and accurate brain MRI segmentation method. MR brain image segmentation is to know the anatomical structure, to identify the abnormalities, and to detect various tissues which help in treatment planning prior to radiation therapy. This proposed technique is a Multilevel Thresholding (MT) method based on the phenomenon of Electromagnetism and it segments the image into three tissues such as White Matter (WM), Gray Matter (GM), and CSF. The approach incorporates skull stripping and filtering using anisotropic diffusion filter in the preprocessing stage. This thresholding method uses the force of attraction-repulsion between the charged particles to increase the population. It is the combination of Electromagnetism-Like optimization algorithm with the Otsu and Kapur objective functions. The results obtained by using the proposed method are compared with the ground-truth images and have given best values for the measures sensitivity, specificity, and segmentation accuracy. The results using 10 MR brain images proved that the proposed method has accurately segmented the three brain tissues compared to the existing segmentation methods such as K-means, fuzzy C-means, OTSU MT, Particle Swarm Optimization (PSO), Bacterial Foraging Algorithm (BFA), Genetic Algorithm (GA), and Fuzzy Local Gaussian Mixture Model (FLGMM).

http://ift.tt/2zvSftc

Comparative Study of Fusogenic Activity of H1 and H5 Subtypes Influenza Virus Hemagglutinins

Influenza virus hemagglutinins are surface proteins responsible for fusion of the viral and cellular membranes. Their capacity to mediate membrane fusion (fusogenic activity) is studied by various methods, including the syncytium formation and pseudovirus transduction methods. We constructed plasmids coding for genes of three H1 and one H5 hemagglutinins and compared their fusogenic activities. Hemagglutinin capacity to induce syncytium formation did not always correlate with the transduction activity of the respective pseudoviruses. Hemagglutinin H5 exhibited high fusogenic activity in studies by both methods, however, two of the studied H1 hemagglutinins induced the formation of syncytia, but did not mediate pseudovirus transduction. This could be due to different capsid sizes of influenza virus and vesicular stomatitis virus, which determines their different permeability through the fusion pore.

http://ift.tt/2yKggQ4

Myocardial Protection against Ischemic and Reperfusion Injuries (Experimental Study)

The effects of hypoxic, hyperoxic, and hypoxic-hyperoxic preconditioning were examined in the prospective study on narcotized and artificially ventilated rabbits. Under artificial circulation, acute myocardial ischemia was modeled by ligation of anterior descending coronary artery, which was followed by reperfusion. The degree of ventricular arrhythmias was assessed, and the ischemic area was evaluated in percent of the area at risk. Microscopic characterization of the myocardium was employed to assess the cardioprotective effect of hypoxic and/or hyperoxic preconditioning. According to Kruskal—Wallis test, the greatest resistance of the myocardium to ischemic and reperfusion injury was observed after hypoxic-hyperoxic preconditioning (H=42.459; p=0.009). The rabbits subjected to this type of preconditioning demonstrated the least damaged myocardium in comparison with nonconditioned controls.

http://ift.tt/2ma2MY2

Specific Features of Electrolyte Excretion at the Early Stages of Arterial Hypertension in SHR Rats

Daytime and nighttime systolic and diastolic BP was recorded in 23-week-old SHR and Wistar rats by telemetric monitoring. Urine concentrations of sodium, potassium, and calcium were determined in SHR rats during of light (07.00-19.00 h) and dark hours (19.00-07.00 h) at the age of 18, 19, 20, 21, 22, and 23 week; 23-week-old Wistar rats were used as the control. At early stages of the experiment, urine sodium concentration was elevated in SHR rats both at daytime and at night. Thereafter, this value declined and by 22-23 week was significantly lower than in normotensive Wistar rats, but only during daytime. Daytime potassium concentration significantly surpassed the control level during weeks 18-19 of the experiment, but later, a tendency to a decrease in this parameter was observed. Daytime calcium content in SHR rats did not significantly differ from the control throughout the experiment. At night, this value exceeded the control level by more than 2 times during weeks 18-19, but then returned to the level observed in normotensive animals.

http://ift.tt/2yLjnHh

Green Tea Extract Increases the Expression of Genes Responsible for Regulation of Calcium Balance in Rat Slow-Twitch Muscles under Conditions of Exhausting Exercise

We studied the role of calcium-regulating structures of slow- (m. soleus, SOL) and fast-twitch (m. extensor digitorum longus, EDL) skeletal muscles of rats during adaptation to exhausting physical activity and the possibility of modulating this adaptation with decaffeinated green tea extract. It was established that EDL adaptation is mainly aimed at Са²⁺ elimination from the sarcoplasm by Са-ATPase and its retention in the reticulum by calsequestrin. Administration of green tea extract increased endurance due to involvement of slow-twitch muscles whose adaptation is associated with enhanced expression of all the studied genes responsible for the regulation of Ca²⁺ balance.

http://ift.tt/2m4thOi

Role of Endogenous Agonists of Opioid Receptors in the Regulation of Heart Resistance to Postischemic Reperfusion Injury

Intravenous injection of nonselective antagonists of opioid receptors (OR) naltrexone (5 mg/kg) and naloxone methiodide (5 mg/kg), selective δ₁-OR antagonist BNTX (0.7 mg/kg), selective δ₂-OR blocker naltriben (0.3 mg/kg), selective κ-OR antagonist norbinaltorphimine (2 mg/kg), and selective blocker of ORL1 opioid receptors JTC-801 (0.1 mg/kg) produced no effect on reperfusion injury to the heart in rats narcotized with α-chloralose. In contrast, selective μ-OR antagonist CTAP (1 mg/kg) limited the infarct size, although this effect was not observed at a lower CTAP concentration of 0.1 mg/kg. Probably, the myocardial infarct size-limiting effect of CTAP was associated with activation of the non-opioid receptors. It was hypothesized that endogenous OR agonists did not affect heart resistance to reperfusion injury in unadapted rats.

http://ift.tt/2yIQXOb

Functional and Biochemical Parameters of Erythrocytes during Mexicor Treatment in Posttraumatic Period after Experimental Blood Loss and Combined Traumatic Brain Injury

Mexicor treatment (8 mg/kg body weight per day) during the posttraumatic period after concomitant traumatic brain injury and acute blood loss in rats increased electrophoretic mobility and concentration of 2,3-diphosphoglycerate, and reduced malondialdehyde content in erythrocytes. These changes improved hemodynamics and oxygen-transporting function of the blood. The most pronounced effects of Mexicor were observed at the early stages of posttraumatic period.

http://ift.tt/2m6Uu31

Correction: Simulation-based multiprofessional obstetric anaesthesia training conducted in situ versus off-site leads to similar individual and team outcomes: a randomised educational trial

Sørensen JL, van der Vleuten C, Rosthøj S, et al. Simulation-based multiprofessional obstetric anaesthesia training conducted in situ versus off-site leads to similar individual and team outcomes: a randomised educational trial. BMJ Open 2015;5:e008344. doi: 10.1136/bmjopen-2015-008344.

The table headings are incorrect on pages 2 and 3 of . The sub-headings should read 'OSS' and 'ISS' - these headings are correct on page 1 of the Table but the wrong way round in pages 2 and 3.

http://ift.tt/2zoejbt

Association between organisational and workplace cultures, and patient outcomes: systematic review

Design and objectives

Every organisation has a unique culture. There is a widely held view that a positive organisational culture is related to positive patient outcomes. Following the Preferred Reporting Items for Systematic Review and Meta-Analyses statement, we systematically reviewed and synthesised the evidence on the extent to which organisational and workplace cultures are associated with patient outcomes.

Setting

A variety of healthcare facilities, including hospitals, general practices, pharmacies, military hospitals, aged care facilities, mental health and other healthcare contexts.

Participants

The articles included were heterogeneous in terms of participants. This was expected as we allowed scope for wide-ranging health contexts to be included in the review.

Primary and secondary outcome measures

Patient outcomes, inclusive of specific outcomes such as pain level, as well as broader outcomes such as patient experience.

Results

The search strategy identified 2049 relevant articles. A review of abstracts using the inclusion criteria yielded 204 articles eligible for full-text review. Sixty-two articles were included in the final analysis. We assessed studies for risk of bias and quality of evidence. The majority of studies (84%) were from North America or Europe, and conducted in hospital settings (89%). They were largely quantitative (94%) and cross-sectional (81%). The review identified four interventional studies, and no randomised controlled trials, but many good quality social science studies. We found that overall, positive organisational and workplace cultures were consistently associated with a wide range of patient outcomes such as reduced mortality rates, falls, hospital acquired infections and increased patient satisfaction.

Conclusions

Synthesised, although there was no level 1 evidence, our review found a consistently positive association held between culture and outcomes across multiple studies, settings and countries. This supports the argument in favour of activities that promote positive cultures in order to enhance outcomes in healthcare organisations.

http://ift.tt/2ztnqVJ

Clinical characteristics and prognosis of drug-associated acute respiratory distress syndrome compared with non-drug-associated acute respiratory distress syndrome: a single-centre retrospective study in Japan

Objectives

To report the clinical features and prognosis of drug-associatedacute respiratory distress syndrome (ARDS).

Design

A retrospective analysis of data collected during a prospective cohort study.

Setting

Intensive care unit in a teaching hospital.

Participants

A total of 197 Japanese patients with ARDS diagnosed by the Berlin definition who were admitted to the Division of Respiratory Medicine from October 2004 to December 2015 were enrolled in the study and were classified as two groups according to their causes: a drug-associated ARDS group (n=27) and a non-drug-associated ARDS group (n=170). Primary outcome measure is 28-day mortality, and the secondaryoutcome measure is ventilator-free days.

Results

The Acute Physiology and Chronic Health Evaluation II scores were significantly lower in the drug-associated ARDS group than in the non-drug-associated ARDS group (median (IQR): 18.0 (16.5–21.0) vs 23.0 (18.0–26.0), p<0.001), and the arterial oxygen tension/fractional inspired oxygen ratio was higher (148.0 (114.1–177.5) vs 101.0 (71.5–134.0), p=0.003). In the drug-associated ARDS group, although high-resolution CT scores indicative of the extent of fibroproliferation (301.6 (244.1–339.8) vs 208.3 (183.4–271.6), p<0.001), serum lactate dehydrogenase levels (477 (365–585) vs 322 (246–434), p=0.003) and the McCabe scores (score 1/2/3, n (%): 20 (74)/4 (15)/3 (11)vs154 (91)/7 (4)/9 (5), p=0.04) were significantly higher, ventilator weaning was earlier (p<0.001) and 28-day mortality was better (p=0.043). After adjusting for potentially confounding covariates, drug-associated ARDS group was associated with lower 28-day mortality (adjusted HR (HR) 0.275; 95% CI 0.106 to 0.711; p=0.008).

Conclusions

Although more severe lung damage with fibroproliferation was observed in patients with drug-associated ARDS, ventilator weaning was earlier, and their prognosis was better than the others. Further well-designed prospective studies are needed.

http://ift.tt/2zpE1fO

Consensus validation of the POSAMINO (POtentially Serious Alcohol-Medication INteractions in Older adults) criteria

Objectives

Older adults are particularly vulnerable to adverse effects from concurrent alcohol and medication use. However, there is limited evidence regarding the prevalence of these adverse outcomes among older adults, and there is a lack of consensus regarding what constitutes an alcohol-interactive medicine. The objective of this study was to develop an explicit list of potentially serious alcohol–medication interactions for use in older adults.

Design

Following a systematic review, review of drug compendia and clinical guidance documents, a two-round Delphi consensus method was conducted.

Setting

Ireland and the United Kingdom (UK), primary care and hospital setting.

Participants

The Project Steering Group developed a list of potentially serious alcohol–medication interactions. The Delphi panel consisted of 19 healthcare professionals (general practitioners, geriatricians, hospital and community pharmacists, clinical pharmacologists and pharmacists, and physicians specialising in substance misuse).

Results

An inventory of 52 potentially serious alcohol–medication interactions was developed by the Project Steering Group. British National Formulary black dot warnings (n=8) were included in the final criteria as they represent 'potentially serious' interactions. The remaining 44 criteria underwent a two-round Delphi process. In the first round, 13 criteria were accepted into the POtentially Serious Alcohol–Medication INteractions in Older adults (POSAMINO) criteria. Consensus was not reached on the remaining 31 criteria; 9 were removed and 8 additional criteria were included following a review of panellist comments. The remaining 30 criteria went to round 2, with 17 criteria reaching consensus, providing a final list of 38 potentially serious alcohol–medication interactions: central nervous system (n=15), cardiovascular system (n=9), endocrine system (n=5), musculoskeletal system (n=3), infections (n=3), malignant disease and immunosuppression (n=2), and respiratory system (n=1).

Conclusions

POSAMINO is the first set of explicit potentially serious alcohol–medication interactions for use in older adults. Following future validation studies, these criteria may allow for the risk stratification of older adults at the point of prescribing.

http://ift.tt/2ztnnJx

A nationwide population-based cohort study of peripartum hysterectomy and arterial embolisation in Belgium: results from the Belgian Obstetric Surveillance System

Objectives

To assess the prevalence of major obstetric haemorrhage managed with peripartum hysterectomy and/or interventional radiology (IR) in Belgium. To describe women characteristics, the circumstances in which the interventions took place, the management of the obstetric haemorrhage, the outcome and additional morbidity of these women.

Design

Nationwide population-based prospective cohort study.

Setting

Emergency obstetric care. Participation of 97% of maternities covering 98.6% of deliveries in Belgium.

Participants

All women who underwent peripartum hysterectomy and/or IR procedures in Belgium between January 2012 and December 2013.

Results

We obtained data on 166 women who underwent peripartum hysterectomy (n=84) and/or IR procedures (n=102), corresponding to 1 in 3030 women undergoing a peripartum hysterectomy and another 1 in 3030 women being managed by IR, thereby preserving the uterus. Seventeen women underwent hysterectomy following IR and three women needed further IR despite hysterectomy. Abnormal placentation and/or uterine atony were the reported causes of haemorrhage in 83.7%. Abnormally invasive placenta was not detected antenatally in 34% of cases. The interventions were planned in 15 women. Three women were transferred antenatally and 17 women postnatally to a hospital with emergency IR service. Urgent peripartum hysterectomy was averted in 72% of the women who were transferred, with no significant difference in need for transfusion. IR procedures were able to stop the bleeding in 87.8% of the attempts. Disseminated intravascular coagulation secondary to major haemorrhage was reported in 32 women (19%).

Conclusion

The prevalence in Belgium of major obstetric haemorrhage requiring peripartum hysterectomy and/or IR is estimated at 6.6 (95% CI 5.7 to 7.7) per 10 000 deliveries. Increased clinician awareness of the risk factors of abnormal placentation could further improve the management and outcome of major obstetric haemorrhage. A case-by-case in-depth analysis is necessary to reveal whether the hysterectomies and arterial embolisations performed in this study were appropriate or preventable.

http://ift.tt/2zqslcq

Impact of UV-irradiation on electrical impedance spectroscopy of benign nevi: study protocol for a prospective, controlled, clinical study

Introduction

The clinical and histological changes of nevi after ultraviolet (UV) irradiation have been studied in detail. In contrast, the impact of UV irradiation on electrical impedance spectroscopy scores of nevi has not been investigated. However, for physicians, it is essential to know the extent to which changes in electrical impedance spectroscopy scores of nevi may be attributed to seasonal effects of UV irradiation.

Methods

This is a prospective, controlled, clinical study evaluating the impact of UV irradiation on the electrical impedance spectroscopy scores of benign nevi in 50 patients undergoing phototherapy. To this end, benign nevi of patients with a medical indication for phototherapy will be measured by electrical impedance spectroscopy before, during and after UV irradiation. At the same time, non-irradiated nevi of the same patient will be measured to account for changes over time that are independent of direct UV irradiation.

Ethics and dissemination

Ethical approval was obtained from the ethics committee of the medical faculty of the University of Heidelberg (ethics approval number S-279/2017). The design and the final results of the study will be published and made available to the public.

Trial registration number

DRKS00012456; Pre-results.

http://ift.tt/2zudcV8

Cohort profile: workers compensation in a changing Australian labour market: the return to work (RTW) study

Purpose

Workers' compensation claims for older workers and workers who have suffered psychological injury are increasing as a proportion of total claims in many jurisdictions. In the Australian state of Victoria, claims from both these groups are associated with higher than average wage replacement and healthcare expenditures. This cohort profile describes a longitudinal study which aims to investigate differences in the return to work (RTW) process for older workers compared with younger workers and claimants with musculoskeletal injuries compared with those with psychological injuries.

Participants

This prospective cohort study involved interviewing workers' compensation claimants at three time points. The cohort was restricted to psychological and musculoskeletal claims. Only claimants aged 18 and over were recruited, with no upper age limit. A total of 869 claimants completed the baseline interview, representing 36% of the eligible claimant population. Ninety-one per cent of participants agreed at baseline to have their survey responses linked to administrative workers' compensation data. Of the 869 claimants who participated at baseline, 632 (73%) took part in the 6-month follow-up interview, and 572 (66%) participated in the 12-month follow-up interview.

Findings to date

Information on different aspects of the RTW process and important factors that may impact the RTW process was collected at the three survey periods. At baseline, participants and non-participants did not differ by injury type or age group, but were more likely to be female and from the healthcare and social assistance industry. The probability of non-participation at follow-up interviews showed younger age was a statistically significant predictor of non-participation.

Future plans

Analysis of the longitudinal cohort will identify important factors in the RTW process and explore differences across age and injury type groups. Ongoing linkage to administrative workers' compensation data will provide information on wage replacement and healthcare service use into the future.

http://ift.tt/2zuikst

Study design and protocol for a mixed methods evaluation of an intervention to reduce and break up sitting time in primary school classrooms in the UK: The CLASS PAL (Physically Active Learning) Programme

Introduction

Children engage in a high volume of sitting in school, particularly in the classroom. A number of strategies, such as physically active lessons (termed movement integration (MI)), have been developed to integrate physical activity into this learning environment; however, no single approach is likely to meet the needs of all pupils and teachers. This protocol outlines an implementation study of a primary school-based MI intervention: CLASS PAL (Physically Active Learning) programme. This study aims to (A) determine the degree of implementation of CLASS PAL, (B) identify processes by which teachers and schools implement CLASS PAL and (C) investigate individual (pupil and teacher) level and school-level characteristics associated with implementation of CLASS PAL.

Methods and analysis

The intervention will provide teachers with a professional development workshop and a bespoke teaching resources website. The study will use a single group before-and-after design, strengthened by multiple interim measurements. Six state-funded primary schools will be recruited within Leicestershire, UK.

Evaluation data will be collected prior to implementation and at four discrete time points during implementation: At measurement 0 (October 2016), school, teacher and pupil characteristics will be collected. At measurements 0 and 3 (June–July 2017), accelerometry, cognitive functioning, self-reported sitting and classroom engagement data will be collected. At measurements 1(December 2016–March 2017) and 3 , teacher interviews (also at measurement 4; September–October 2017) and pupil focus groups will be conducted, and at measurements 1 and 2 (April–May 2017), classroom observations. Implementation will be captured through website analytics and ongoing teacher completed logs.

Ethics and dissemination

Ethical approval was obtained through the Loughborough University Human Participants Ethics Sub-Committee (Reference number: R16-P115). Findings will be disseminated via practitioner and/or research journals and to relevant regional and national stakeholders through print and online media and dissemination event(s).

http://ift.tt/2zpvTM6

Validation of an automated delirium prediction model (DElirium MOdel (DEMO)): an observational study

Objectives

Delirium is an underdiagnosed, severe and costly disorder, and 30%–40% of cases can be prevented. A fully automated model to predict delirium (DEMO) in older people has been developed, and the objective of this study is to validate the model in a hospital setting.

Setting

Secondary care, one hospital with two locations.

Design

Observational study.

Participants

The study included 450 randomly selected patients over 60 years of age admitted to Zuyderland Medical Centre. Patients who presented with delirium on admission were excluded.

Primary outcome measures

Development of delirium through chart review.

Results

A total of 383 patients were included in this study. The analysis was performed for delirium within 1, 3 and 5 days after a DEMO score was obtained. Sensitivity was 87.1% (95% CI 0.756 to 0.939), 84.2% (95% CI 0.732 to 0.915) and 82.7% (95% CI 0.734 to 0.893) for 1, 3 and 5 days, respectively, after obtaining the DEMO score. Specificity was 77.9% (95% CI 0.729 to 0.882), 81.5% (95% CI 0.766 to 0.856) and 84.5% (95% CI 0.797 to 0.884) for 1, 3 and 5 days, respectively, after obtaining the DEMO score.

Conclusion

DEMO is a satisfactory prediction model but needs further prospective validation with in-person delirium confirmation. In the future, DEMO will be applied in clinical practice so that physicians will be aware of when a patient is at an increased risk of developing delirium, which will facilitate earlier recognition and diagnosis, and thus will allow the implementation of prevention measures.

http://ift.tt/2zudbAy

Association of type 2 diabetes with in-hospital complications among women undergoing breast cancer surgical procedures. A retrospective study using the Spanish National Hospital Discharge Database, 2013-2014

Objectives

To compare the type of surgical procedures used, comorbidities, in-hospital complications (IHC) and in-hospital outcomes between women with type 2 diabetes mellitus (T2DM) and age-matched women without diabetes who were hospitalised with breast cancer. In addition, we sought to identify factors associated with IHC in women with T2DM who had undergone surgical procedures for breast cancer.

Design

Retrospective study using the National Hospital Discharge Database, 2013–2014.

Setting

Spain.

Participants

Women who were aged ≥40 years with a primary diagnosis of breast cancer and who had undergone a surgical procedure. We grouped admissions by T2DM status. We selected one matched control for each T2DM case.

Main outcome measures

The type of procedure (breast-conserving surgery (BCS) or mastectomy), clinical characteristics, complications, length of hospital stay and in-hospital mortality.

Results

We identified 41 458 admissions (9.23% with T2DM). Overall, and in addition to the surgical procedure, we found that comorbidity, hypertension and obesity were more common among patients with T2DM. We also detected a higher incidence of mastectomy in women with T2DM (44.69% vs 42.42%) and a greater rate of BCS in patients without T2DM (57.58% vs 55.31%). Overall, non-infectious complications were more common among women with T2DM (6.40% vs 4.56%). Among women who had undergone BCS or a mastectomy, IHC were more frequent among diabetics (5.57% vs 3.04% and 10.60% vs 8.24%, respectively). Comorbidity was significantly associated with a higher risk of IHC in women with diabetes, independent of the specific procedure used.province

Conclusions

Women with T2DM who undergo surgical breast cancer procedures have more comorbidity, risk factors and advanced cancer presentations than matched patients without T2DM. Mastectomies are more common in women with T2DM. Moreover, the procedures among women with T2DM were associated with greater IHC. Comorbidity was a strong predictor of IHC in women with T2DM.

http://ift.tt/2zp9fDG

Cohort profile: design and first results of the Dutch IBD Biobank: a prospective, nationwide biobank of patients with inflammatory bowel disease

Purpose

The Dutch IBD Biobank aims to facilitate the discovery of predictors for individual disease course and treatment response in patients with inflammatory bowel disease (IBD). In this paper, we aim to describe the establishment of the Dutch IBD Biobank, including the facilitators and barriers to establishment. Moreover, we aim to provide a complete overview of the content of the Dutch IBD Biobank.

Participants

Since 2007, every patient with IBD treated in one of the eight Dutch university medical centres is asked to participate in the Dutch IBD Biobank in which 225 standardised IBD-related data items and biomaterials, such as serum, DNA, biopsies and a stool sample, are collected.

Findings to date

As of June 2014, the Dutch IBD Biobank had enrolled 3388 patients with IBD: 2118 Crohn's disease (62.5%), 1190 ulcerative colitis (35.1%), 74 IBD-unclassified (2.2%) and 6 IBD-indeterminate (0.2%). The inclusion of patients with IBD is ongoing. The quality of the biomaterials is good and serum, DNA and biopsies have been used in newly published studies.

Future plans

The genotyping (750 000 genetic variants) of all participants of the Dutch IBD Biobank is currently ongoing, enabling more genetic research. In addition, all participants will start reporting disease activity and outcome measures using an online platform and mobile app.

http://ift.tt/2zu9ye0

Qualitative study to understand the barriers to recruiting young people with cancer to BRIGHTLIGHT: a national cohort study in England

Objectives

BRIGHTLIGHT is a national evaluation of cancer services for teenagers and young adults in England. Following challenges with recruitment, our aim was to understand more fully healthcare professionals' perspectives of the challenges of recruiting young people to a low-risk observational study, and to provide guidance for future recruitment processes.

Design

Qualitative.

Setting

National Health Service (NHS) hospitals in England.

Methods

Semistructured telephone interviews with a convenience sample of 23 healthcare professionals. Participants included principal investigators/other staff recruiting into the BRIGHTLIGHT study. Data were analysed using framework analysis.

Results

The emergent themes were linked to levels of research organisational management, described using the levels of social network analysis: micro-level (the individual; in this case the target population to be recruited—young people with cancer); meso-level (the organisation; refers to place of recruitment and people responsible for recruitment); and macro-level (the large-scale or global structure; refers to the wider research function of the NHS and associated policies). Study-related issues occurred across all three levels, which were influenced by the context of the study. At the meso-level, professionals' perceptions of young people and communication between professionals generated age/cancer type silos, resulting in recruitment of either children or adults, but not both by the same team, and only in the cancer type the recruiting professional was aligned to. At the macro-level the main barrier was discordant configuration of a research service with a clinical service.

Conclusions

This study has identified significant barriers to recruitment mainly at the meso-level and macro-level, which are more challenging for research teams to influence. We suggest that interconnected whole-system changes are required to facilitate the success of interventions designed to improve recruitment. Interventions targeted at study design/management and the micro-level only may be less successful. We offer solutions to be considered by those involved at all levels of research for this population.

http://ift.tt/2zp97nG

Quality of reporting of pilot and feasibility cluster randomised trials: a systematic review

Objectives

To systematically review the quality of reporting of pilot and feasibility of cluster randomised trials (CRTs). In particular, to assess (1) the number of pilot CRTs conducted between 1 January 2011 and 31 December 2014, (2) whether objectives and methods are appropriate and (3) reporting quality.

Methods

We searched PubMed (2011–2014) for CRTs with 'pilot' or 'feasibility' in the title or abstract; that were assessing some element of feasibility and showing evidence the study was in preparation for a main effectiveness/efficacy trial. Quality assessment criteria were based on the Consolidated Standards of Reporting Trials (CONSORT) extensions for pilot trials and CRTs.

Results

Eighteen pilot CRTs were identified. Forty-four per cent did not have feasibility as their primary objective, and many (50%) performed formal hypothesis testing for effectiveness/efficacy despite being underpowered. Most (83%) included 'pilot' or 'feasibility' in the title, and discussed implications for progression from the pilot to the future definitive trial (89%), but fewer reported reasons for the randomised pilot trial (39%), sample size rationale (44%) or progression criteria (17%). Most defined the cluster (100%), and number of clusters randomised (94%), but few reported how the cluster design affected sample size (17%), whether consent was sought from clusters (11%), or who enrolled clusters (17%).

Conclusions

That only 18 pilot CRTs were identified necessitates increased awareness of the importance of conducting and publishing pilot CRTs and improved reporting. Pilot CRTs should primarily be assessing feasibility, avoiding formal hypothesis testing for effectiveness/efficacy and reporting reasons for the pilot, sample size rationale and progression criteria, as well as enrolment of clusters, and how the cluster design affects design aspects. We recommend adherence to the CONSORT extensions for pilot trials and CRTs.

http://ift.tt/2ztrAgn

Diagnostic utility of appetite loss in addition to existing prediction models for community-acquired pneumonia in the elderly: a prospective diagnostic study in acute care hospitals in Japan

Objective

Diagnosis of community-acquired pneumonia (CAP) in the elderly is often delayed because of atypical presentation and non-specific symptoms, such as appetite loss, falls and disturbance in consciousness. The aim of this study was to investigate the external validity of existing prediction models and the added value of the non-specific symptoms for the diagnosis of CAP in elderly patients.

Design

Prospective cohort study.

Setting

General medicine departments of three teaching hospitals in Japan.

Participants

A total of 109 elderly patients who consulted for upper respiratory symptoms between 1 October 2014 and 30 September 2016.

Main outcome measures

The reference standard for CAP was chest radiograph evaluated by two certified radiologists. The existing models were externally validated for diagnostic performance by calibration plot and discrimination. To evaluate the additional value of the non-specific symptoms to the existing prediction models, we developed an extended logistic regression model. Calibration, discrimination, category-free net reclassification improvement (NRI) and decision curve analysis (DCA) were investigated in the extended model.

Results

Among the existing models, the model by van Vugt demonstrated the best performance, with an area under the curve of 0.75(95% CI 0.63 to 0.88); calibration plot showed good fit despite a significant Hosmer-Lemeshow test (p=0.017). Among the non-specific symptoms, appetite loss had positive likelihood ratio of 3.2 (2.0–5.3), negative likelihood ratio of 0.4 (0.2–0.7) and OR of 7.7 (3.0–19.7). Addition of appetite loss to the model by van Vugt led to improved calibration at p=0.48, NRI of 0.53 (p=0.019) and higher net benefit by DCA.

Conclusions

Information on appetite loss improved the performance of an existing model for the diagnosis of CAP in the elderly.

http://ift.tt/2zntXnj

Developing a classification system for haemoglobin management in patients with end-stage renal disease on haemodialysis: a secondary data analysis

Background

Ongoing discussion on anaemia management and target haemoglobin (Hb) levels in patients on haemodialysis with erythropoietin treatment require a systematic approach in evaluating current practice. Aim of the present study was to develop a new classification system to easily monitor Hb trajectories and categorise patients on haemodialysis.

Methods

Routine data from five dialysis centres in the USA collected between 2010 and 2016. Data were anonymised and only those from patients with fortnightly Hb values were included in the analysis. Entries on blood parameters and medication were standardised to achieve overall comparability. Data from each patient was grouped in periods of 120 days. Hb values above or below the target level of 10–12 g/dL were counted for each period. Periods were then assigned to Hb-classes according to the number of Hb values out of range per period: Hb-class I with 0–2, Hb-class II for 3–5 and Hb-class III for ≥6 values out of range.

Results

Records from 3349 patients with fortnightly Hb values, information on haemodialysis data, laboratory parameters correlated to red blood cells and data on medication with erythropoiesis-stimulating agents (ESAs) were available. Patients were 64.4±15.9 years old; 55.0% were men. Statistical analysis revealed significant differences between Hb-classes in all of the examined parameters, except erythrocytes mean corpuscular volume and C reactive protein above the threshold, with more critical values in higher Hb-classes. The usage of ESAs showed a mean difference between Hb-class III and Hb-class I of 6.4 units/day and kilogram body weight in a 120-day period.

Conclusion

Our classification system allows an easily achievable overview of the patients' responsiveness and performance of Hb management. Integrated into a disease management programme or continuous quality improvement, the classification delivers an instant appraisal without complex statistical or mathematical processing.

http://ift.tt/2zu9xXu

Contribution of the voluntary sector to mental health crisis care in England: protocol for a multimethod study

Introduction

Timely access to the right kind of support for people experiencing a mental health crisis can be problematic. The voluntary sector (VS) plays a key role in providing support and enabling access, but there is a knowledge gap concerning its contribution and interface with public services in mental health crisis care. This study aims to address this.

Methods and analysis

The study has three empirical elements: (1) a national survey of voluntary sector organisations (VSOs) in England and national stakeholder interviews to develop a typology of organisations and interventions provided by VSOs; (2) detailed mapping of VS services in two regions through interviews and extending the national survey; (3) four case studies, identified from the regional mapping, of VS mental health crisis services and their interface with National Health Service (NHS) and local authority services, at both a system and individual level. Data collection will involve interviews with commissioners; VSO and NHS or local authority providers; and focus groups with people who have experience of VSO crisis support, both service users and carers; and mapping the crisis trajectory of 10 service users in each study site through narrative interviews with service users and informal carers to understand the experience of VSO crisis care and its impact.

Ethics and dissemination

The University of Birmingham Humanities and Social Sciences Ethical Review Committee granted ethical approval (reference ERN_16–1183) for the national and regional elements of the study. Ethical review by the Health Research Authority will be required for the case study research once the sites have been identified from the first two elements of the study. A range of methods including a policy seminar, publication in academic journals and a tool kit for commissioners and practitioners will be produced to maximise the impact of the findings on policy and practice.

http://ift.tt/2zpL08d

Impact of prenatal diagnosis on survival of newborns with four congenital heart defects: a prospective, population-based cohort study in France (the EPICARD Study)

Objectives

(1) Assess the population-level probability of prenatal diagnosis and termination of pregnancy for fetal anomaly for four major congenital heart defects; (2) Examine, using population-based data, the relation between timing of (prenatal vs postnatal) diagnosis and risk of infant (ie, < 1 year) mortality for four major congenital heart defects (CHDs).

Design

Population-based cohort (the EPIdémiologie des CARDiopathies congénitales) study.

Setting

Greater Paris area (Paris and its surrounding suburbs).

Patients

Three hundred and fifty-four cases of four major CHDs, including functionally univentricular heart (FUH, N=132), d-transposition of great arteries (d-TGA, N=85), tetralogy of Fallot (TOF, N=60) and coarctation of aorta (CoA, N=77). Statistical analysis included the Mantel-Haenszel method and a test of homogeneity of risk ratios.

Results

Approximately 95% of FUH, more than two-thirds of d-TGA and TOF, and 40% of CoA were prenatally diagnosed. Overall, we did not find any statistically significant association between timing of (prenatal vs postnatal) diagnosis of CHD and risk of infant mortality (Mantel-Haenszel risk ratio 1.1, 95% CI 0.5 – 2.7); and the differences between the risk ratios of the association between prenatal diagnosis and infant mortality across the four CHDs was not statistically significant.

Conclusion

These results imply that at least in the settings where specialised services are readily available, survival may no longer be the most relevant outcome, or the best criterion, for evaluating the impact of prenatal diagnosis on the outcome of CHD. The beneficial effects of prenatal diagnosis may be better sought by looking at more 'subtle' or long-term neurodevelopmental outcomes.

http://ift.tt/2ztrsgT

Study protocol for the Cities Changing Diabetes programme: a global mixed-methods approach

Introduction

Urban living has been shown to affect health in various ways. As the world is becoming more urbanised and almost two-thirds of people with diabetes now live in cities, research into the relationship between urban living, health and diabetes is key to improving the lives of many. The majority of people with diabetes have type 2 diabetes, a subset linked to overweight and obesity, decreased physical activity and unhealthy diets. Diabetes has significant consequences for those living with the condition as well as their families, relationships and wider society. Although care and management are improving, complications remain common, and diabetes is among the leading causes of vision loss, amputation, neuropathy and renal and cardiovascular disease worldwide. We present a research protocol for exploring the drivers of type 2 diabetes and its complications in urban settings through the Cities Changing Diabetes (CCD) partnership programme.

Methods and analysis

A global study protocol is implemented in eight collaborating CCD partner cities. In each city, academic institutions, municipal representatives and local stakeholders collaborate to set research priorities and plan implementation of findings. Local academic teams execute the study following the global study protocol presented here. A quantitative Rule of Halves analysis obtains measures of the magnitude of the diabetes burden, the diagnosis rates in each city and the outcomes of care. A qualitative Diabetes Vulnerability Assessment explores the urban context in vulnerability to type 2 diabetes and identifies social factors and cultural determinants relevant to health, well-being and diabetes.

Ethics and dissemination

The protocol steers the collection of primary and secondary data across the study sites. Research ethics board approval has been sought and obtained in each site. Findings from each of the local studies as well as the result from combined multisite (global) analyses will be reported in a series of core scientific journal papers.

http://ift.tt/2znYUIa

A population-based case-control study of hospitalisation due to head injuries among bicyclists and motorcyclists in Taiwan

Introduction

According to official statistics in Taiwan, the main body region of injury causing bicyclist deaths is the head, and bicyclists are 2.6 times more likely to be fatally injured than motorcyclists. There is currently a national helmet law for motorcyclists but not for bicyclists.

Objectives

The primary aim of this study was to determine whether bicyclist casualties have higher odds of head-related hospitalisation than motorcyclists. This study also aims to investigate the determinants of head injury-related hospitalisation among bicyclists and motorcyclists.

Methods

Using linked data from the National Traffic Accident Dataset and the National Health Insurance Research Database for the period 2003–2012, this study investigates the crash characteristics of bicyclist and motorcyclist casualties presenting to hospitals due to motor vehicle crashes. Head injury-related hospitalisation was used as the study outcome for both road users to evaluate whether various factors (eg, human attributes, road and weather conditions, vehicle characteristics) are related to hospital admission of those who sustained serious injuries.

Results

Among 1 239 474 bicyclist and motorcyclist casualties, the proportion of bicyclists hospitalised for head injuries was higher than that of motorcyclists (10.0% vs 6.5%). However, the multiple logistic regression model shows that, after adjustment of this result for other factors such as helmet use, bicyclists were 18% significantly less likely to be hospitalised for head injuries than motorcyclists (AOR 0.82, 95% CI 0.79 to 0.85). Other important determinants of head injury-related hospitalisation for bicyclists and motorcyclists include female riders, elderly riders, crashes occurring in rural areas, moped riders, riding unhelmeted, intoxicated bicyclists and motorcyclists, unlicensed motorcyclists, dusk and dawn conditions and single-vehicle crashes.

Conclusions

Our finding underscores the importance of helmet use in reducing hospitalisation due to head injuries among bicyclists while current helmet use is relatively low.

http://ift.tt/2ztUxsH

Impact of heterogeneity and effect size on the estimation of the optimal information size: analysis of recently published meta-analyses

Objective

To estimate the proportion of systematic reviews that meet the optimal information size (OIS) and assess the impact heterogeneity and effect size have on the OIS estimate by type of outcome (eg, mortality, semiobjective or subjective).

Methods

We carried out searches of Medline and Cochrane to retrieve meta-analyses published in systematic reviews from 2010 to 2012. We estimated the OIS using Trial Sequential Analysis software (TSA V.0.9) and based on several heterogeneity and effect size scenarios, stratifying by type of outcome (mortality/semiobjective/subjective) and by Cochrane/non-Cochrane reviews.

Results

We included 137 meta-analyses out of 218 (63%) potential systematic reviews (one meta-analysis from each systematic review). Of these reviews, 83 (61%) were Cochrane and 54 (39%) non-Cochrane. The Cochrane reviews included a mean of 6.5 (SD 6.1) studies and the non-Cochrane included a mean of 13.2 (SD 10.2) studies. The mean number of patients was 2619.1 (SD 6245.8 or median 586.0) for the Cochrane and 19 888.5 (SD 32 925.7 or median 6566.5) patients for the non-Cochrane reviews. The percentage of systematic reviews that achieved the OIS for all-cause mortality outcome were 0% Cochrane and 25% for non-Cochrane reviews; for semiobjective outcome 17% for Cochrane and 46% for non-Cochrane reviews and for subjective outcome 45% for Cochrane and 72% for non-Cochrane reviews.

Conclusions

The number of systematic reviews that meet an optimal information size is low and varies depending on the type of outcome and the type of publication. Less than half of primary outcomes synthesised in systematic reviews achieve the OIS, and therefore the conclusions are subject to substantial uncertainty.

http://ift.tt/2zqFUIQ

Mise en ligne du N° 5, volume 62 (octobre 2017) de la revue 'Annales de chirurgie plastique esthétique'

Vol 62 - N°5 - octobre 2017 Le renouveau des liftings cervicofaciaux P. 345-599 © 2017, Elsevier Masson SAS

http://ift.tt/2hWbqEG

Pharmacokinetics of RP5063 Following Single Doses to Normal Healthy Volunteers and Multiple Doses Over 10 Days to Stable Schizophrenic Patients

Abstract

RP5063, a multimodal dopamine (D)–serotonin (5-HT) stabilizer, possesses high affinity for D_2/3/4 and 5-HT_{1A/2A/2B/2C/6/7} receptors and moderate affinity for the serotonin transporter. Two phase I studies characterized the pharmacokinetics of a single dose (10 and 15 mg fasting, 15 mg fed/fasting) in healthy volunteers and multiple doses (10, 20, 50, and 100 mg fed) over 10 days in patients with stable schizophrenia. RP5063 displayed a dose-dependent C_max at 4 to 6 h, linear dose proportionality for both C_max and AUC, and a half-life between 40 and 71 h. In the single-dose study, food slightly increased the extent of drug absorption. In the multiple-dose study, steady-state was approached after 120 h of daily dosing. Pooled data in the single-dose study indicate that the pharmacokinetic profile appears to be comparable between Japanese and Caucasians. RP5063 appears to have a straightforward pharmacokinetic profile that supports for phase II and III evaluation as a once-daily oral administered agent.

http://ift.tt/2Aow72S

Effects of Bone Marrow Multipotent Mesenchymal Stromal Cells and Their Secretion Products on the Cellular Composition of the Thymus and Spleen of Female Wistar Rats with Experimental Chronic Inflammation of the Internal Genitals

The effects of bone marrow multipotent mesenchymal stromal cells and their secretion products on the subpopulation composition of thymic and splenic lymphocytes were studied in female Wistar rats with experimental chronic inflammatory process in the internal genitals. Stromal cells and medium conditioned by these cells in different administration routes (intravenous or lymphotropic injection) produces different modulating effect on blood leukocyte count and on subpopulation composition of the splenic and thymic lymphocytes. The most manifest anti-inflammatory effect was observed after lymphotropic injection of multipotent mesenchymal stromal cells creating a high concentration and long persistence of the factors produced by these cells in the focus of inflammation.

http://ift.tt/2hUar8g

Comparative Analysis of Quantitative Parameters of Expression of the Retinoic Acid Nuclear Receptor RARα Gene and APE1/YB-1/MDR1 Pattern Genes in Patients with Newly Detected Multiple Myeloma

The expression of retinoic acid nuclear receptor gene RARα and its relationship with expression of APE1, YB-1, and MDR1 genes was studied in bone marrow aspiration biopsy specimens from 22 patients with newly detected multiple myeloma. The expression of RARα directly correlated with the expression of APE1/YB-1/MDR1 pattern genes. Groups differing by expression of RARα exhibited significant differences in the overall survival of patients; concordant and simultaneous changes in the expression of all genes of the APE1/YB-1/MDR1 pattern suggested the level of RARα gene expression as a potential prognostic factor in the pathogenesis of multiple myeloma.

http://ift.tt/2AnaPmv

Results of Experimental Ligation of the Main Vein with the Use of Cell Technologies

Autologous multipotent mesenchymal stromal cells (MMSC) of bone marrow origin with transfected GFP gene and additionally stained cell membranes were injected to rats through the skin in the projection of ligated femoral vein. The results were evaluated by fluorescent microscopy. No signs of MMSC incorporation into the wall of ligated vessel or reorganized collaterals were detected. Angiogenesis processes involving MMSC were detected in experimental rats within just 4 days and progressed until week 2 postinjection, mainly in granulations at the site of surgical intervention and the cicatrix forming there. Injected MMSC completely formed all tunics of the new vessels and incorporated in the vessels forming from the recipient cells. MMSC and the objects created from them were gradually eliminated with participation of macrophages and replaced by structures formed from the recipient cells.

http://ift.tt/2hWHxnK

Comparative Study of Toxicity of Alkoxyamines In Vitro and In Vivo

Effect of alkoxyamines on normal and tumor cells was studied in vitro and in vivo. In vitro experiments showed that alkoxyamines produce a dose-dependent toxic effect on cells of human breast tumor MCF7 line. Transplantation of Krebs-2 ascites carcinoma cells preincubated with alkoxyamines to mice did not induce tumor growth. An opposite effect was observed in normal mouse cells: functional activity of peritoneal macrophages increased. The possibility of using alkoxyamines as theranostic agents is discussed.

http://ift.tt/2AlQBJM

Balance of Fatty Acids and Their Correlations with Parameters of Lipid Metabolism and Markers of Inflammation in Men with Coronary Atherosclerosis

We studied the balance of fatty acids and their correlation with parameters of lipid metabolism and inflammation markers in men with coronary atherosclerosis. In the blood of patients and healthy men, the content of myristic (C14:0), pentadecanoic (C15:0), palmitic (C16:0), stearic (C18:0), arachidic (C20:0) and docosanic (C22:0), TNFα, IL-1β, IL-6, IL-8, C-reactive protein, cholesterol, triglycerides, HDL, and LPO intensity were measured. In patients with coronary atherosclerosis, increased concentrations of saturated fatty acids, triglycerides, LPO products, IL-6, IL-8, and C-reactive protein were found. Correlation analysis revealed multiple correlations between the studied fatty acids, correlation of C16:0, C18:0, and C20:0 with inflammation markers, C14:0, C16:0, and C18:0 with triglyceride level, C16:0, C18:0, and C20:0 with cholesterol. The contents of C14:0, C15:0, C16:0, and C18:0 correlated with the presence of coronary atherosclerosis. Lipid metabolism disturbances in coronary atherosclerosis were accompanied by changes in not only lipid spectrum and inflammation markers, but also fatty acids balance.

http://ift.tt/2hU15sW

In Vitro Culturing and Storage of Campylobacter Genus Bacteria

Experimental model for in vitro evaluation of Campylobacter genus bacteria growth kinetics, inhibition, or inactivation is proposed. The model allows quantitative evaluation of the sensitivity to various types of stress exposure and promotes detection of the regularities of their transformation into uncultivable forms. The model implies the use of 96-well plates for parallel culturing of several subpopulations of the test strain in media with various parameters. The proposed algorithm includes evaluation of the proportion of viable CFU to total level of planktonic and uncultivable cells in the population, which is estimated by the content of genomic DNA in the samples by quantitative PCR (or real-time PCR) with ciaB, cdtB, or 16S rRNA primers. The presence of biofilm matrix is detected by the intensity of staining of polystyrene plates. This model can be used for evaluation of the most significant types of exposure, including low-dose antibacterial treatment, promoting the formation of stable microorganism variants. The model has been used to study the effects of culturing conditions on the characteristics of C. jejuni populations. The most characteristic feature of C. jejuni is reduction of the count of viable cells up to complete disappearance of cultivable forms under favorable conditions of growth. The level of viable cells in the populations decreased 10-fold and more, on average, after 48-h incubation. Not all strains exhibit this property, some strains retain their viability, which is detected by the culturing method, and contributes to biofilm formation.

http://ift.tt/2AmxmQ4

Potentialities of MicroRNA Diagnosis in Patients with Bladder Cancer

Despite promising vista of the use of microRNA in molecular diagnosis of bladder cancer, there are few data on their expression profiles, which impedes assessment of diagnostic value of these marker molecules. In this study, suppression subtractive hybridization, on-chip hybridization, and high-throughput deep sequencing focused on profiling microRNA and assessing the diagnostic value of revealed marker molecules.

http://ift.tt/2hVI0GR

Morphofunctional State of Erythrocytes in Rats with Walker-256 Carcinoma Treated with Docetaxel and Xymedon

We compared the effect of xymedon (100 mg/kg) and Mexidol (50 mg/kg) on morphometric parameters of erythrocytes and oxygen-transporting function of hemoglobin in rats with Walker-256 carcinoma treated with docetaxel (15 mg/kg once intraperitoneally on day 11 after tumor cells transplantation). Xymedon and Mexidol were injected intramuscularly for 10 days starting from day 11 of the experiment. The studied parameters were evaluated on experimental days 14 and 22. Similar to Mexidol, xymedon prevented changes in the erythrocyte geometric parameters induced by docetaxel and neoplastic process, but increased hemoglobin packing density in erythrocytes (by 32%) more effectively than Mexidol. Optimization of oxygen-transporting function of hemoglobin and normalization of its structural and functional parameters changed by docetaxel treatment (content of oxyhemoglobin, hemoglobin affinity for oxygen and its ability to bind and release oxygen, intensity of symmetric and asymmetric vibrations of pyrrole rings) in rats receiving xymedon took longer time than in case of Mexidol treatment, but the effects were similar.

http://ift.tt/2AlAfks

The Effectiveness of Art Therapy for Teaching Social Skills to Children With Autism Spectrum Disorder

.


http://ift.tt/2zpricY

Evaluating the Impact of a Brief Artistic Intervention on Cardiovascular Recovery From Acute Stress

.


http://ift.tt/2zGWuF7

Art Therapy and Art Museum Education: A Visitor-Focused Collaboration

.


http://ift.tt/2zprhFW

Impact of improved attenuation correction featuring a bone atlas and truncation correction on PET quantification in whole-body PET/MR

Abstract

Purpose

Recent studies have shown an excellent correlation between PET/MR and PET/CT hybrid imaging in detecting lesions. However, a systematic underestimation of PET quantification in PET/MR has been observed. This is attributable to two methodological challenges of MR-based attenuation correction (AC): (1) lack of bone information, and (2) truncation of the MR-based AC maps (μmaps) along the patient arms. The aim of this study was to evaluate the impact of improved AC featuring a bone atlas and truncation correction on PET quantification in whole-body PET/MR.

Methods

The MR-based Dixon method provides four-compartment μmaps (background air, lungs, fat, soft tissue) which served as a reference for PET/MR AC in this study. A model-based bone atlas provided bone tissue as a fifth compartment, while the HUGE method provided truncation correction. The study population comprised 51 patients with oncological diseases, all of whom underwent a whole-body PET/MR examination. Each whole-body PET dataset was reconstructed four times using standard four-compartment μmaps, five-compartment μmaps, four-compartment μmaps + HUGE, and five-compartment μmaps + HUGE. The SUV_max for each lesion was measured to assess the impact of each μmap on PET quantification.

Results

All four μmaps in each patient provided robust results for reconstruction of the AC PET data. Overall, SUV_max was quantified in 99 tumours and lesions. Compared to the reference four-compartment μmap, the mean SUV_max of all 99 lesions increased by 1.4 ± 2.5% when bone was added, by 2.1 ± 3.5% when HUGE was added, and by 4.4 ± 5.7% when bone + HUGE was added. Larger quantification bias of up to 35% was found for single lesions when bone and truncation correction were added to the μmaps, depending on their individual location in the body.

Conclusion

The novel AC method, featuring a bone model and truncation correction, improved PET quantification in whole-body PET/MR imaging. Short reconstruction times, straightforward reconstruction workflow, and robust AC quality justify further routine clinical application of this method.

http://ift.tt/2zuJ7VD

Large-Scale Low-Cost NGS Library Preparation Using a Robust Tn5 Purification and Tagmentation Protocol

Efficient preparation of high quality sequencing libraries that represent well the biological sample is a key step for using next-generation sequencing in research. Tn5 enables fast, robust, and highly efficient processing of limited input material while scaling to the parallel processing of hundreds of samples. Here, we present a robust Tn5 transposase purification strategy based on an N-terminal His₆-Sumo3 tag. We demonstrate that libraries prepared with our in-house Tn5 are of the same quality as those processed with a commercially available kit (Nextera XT), while they reduce the cost of large-scale experiments dramatically. We introduce improved purification strategies for two versions of the Tn5 enzyme. The first version carries the previously reported point mutations E54K and L372P and stably produces libraries of constant fragment size distribution, even if the Tn5-to-input molecule ratio varies. The second Tn5 construct carries an additional point mutation (R27S) in the DNA-binding domain. This construct allows for adjusting the fragment size distribution based on enzyme concentration during tagmentation, a feature that opens new opportunities for use of Tn5 in customized experimental designs. We demonstrate the versatility of our Tn5 enzymes in different experimental settings, including a novel single cell polyadenylation site mapping protocol as well as ultra-low input DNA sequencing.

http://ift.tt/2AnSLID

Venous collapse regulates intracranial pressure in upright body positions

Recent interest in intracranial pressure (ICP) in the upright posture has revealed that the mechanisms regulating postural changes in ICP are not fully understood. We have suggested an explanatory model where the postural changes in ICP depend on well-established hydrostatic effects in the venous system and where these effects are interrupted by collapse of the internal jugular veins (IJVs) in more upright positions. The aim of this study was to investigate this relationship by simultaneous invasive measurements of ICP, venous pressure and IJV collapse in healthy volunteers. ICP (monitored via the lumbar route), central venous pressure (PICC-line) and IJV cross-sectional area (ultrasound) were measured in 11 healthy volunteers (47±10 years) in seven positions, from supine to sitting (0°-69°). Venous pressure and anatomical distances were used to predict ICP in accordance with the explanatory model, and IJV area was used to assess IJV collapse. The hypothesis was tested by comparing measured ICP to predicted ICP. Our model accurately described the general behavior of the observed postural ICP changes (mean difference: -0.03±2.7 mmHg). No difference was found between predicted and measured ICP for any tilt-angle (p-values: 0.65 - 0.94). The results support the hypothesis that postural ICP changes are governed by hydrostatic effects in the venous system and IJV collapse. This improved understanding of the postural ICP regulation may have important implications for the development of better treatments for neurological and neurosurgical conditions affecting ICP.

http://ift.tt/2hVw08d

The orchestration of autonomous and behavioral thermoregulation

There seems to be an efficient order in the recruitment of thermo-effectors, which allows for body temperature regulation at minimal cost of nutrients and water. But how does thermal behaviour fit in this order? In this edition Schlader et al. hypothesized that thermal behavior fits in the orderly recruitment of thermo-effectors as follows: 1) vasomotor responses, 2) behavioral responses, and 3) sweating or metabolic responses. Their results support this hypothesis by showing consistently for heating and cooling that non-glabrous skin blood flow changes immediately with changes in skin temperature, followed by the initiation of a behavioral response. The editorial focus is on old and new questions that are raised by the findings of Schlader et al, and how they pave the way to better understand the underlying regulatory and integrative human physiology of thermoregulation.

http://ift.tt/2AlMv4m

Role of Immune Factors in Angiotensin II-Induced Hypertension and Renal Damage in Dahl Salt-Sensitive Rats

The present study assessed the importance of immunity in AngII (5 ng/kg/min, iv)-mediated hypertension in Dahl Salt Sensitive (SS) rats and SS rats deficient in T- and B-lymphocytes (SS ^Rag1-/-) fed a 0.4% NaCl diet. Baseline mean arterial blood pressure (MAP) was not different between groups. AngII infusion significantly increased MAP in both groups; though MAP increased more rapidly in SS, and the maximal MAP achieved in SS (190±3 mmHg) was significantly greater than that in SS^Rag1-/- (177±3 mmHg) after 12 days. Renal damage, as assessed by albumin excretion rate, was significantly increased after 12 days of AnglI infusion in the SS (from 32±4 to 81±9 mg/day) and in the SS^Rag1-/- (from 12±2 to 51±8 mg/day); albumin excretion rate was significantly different between the SS and SS^Rag1-/- rats at all points measured. Following 9 days of recovery from AngII, MAP was decreased to a greater extent in SS^Rag1-/- (143±5 mmHg) than in SS (157±8 mmHg) when compared to the peak MAP during AngII infusion. At this same time point, the albumin excretion rate of SS^Rag1-/- was significantly lower (42±8 mg/day) than that observed in the SS (66±7 mg/day). Further studies demonstrated that the kidneys of AngII-treated SS had increased CD45+ total leukocytes, CD11b/c+ macrophages/monocytes, and CD3+ T Cells compared to vehicle-treated SS. The present data suggest that infiltrating T cells in the kidney exacerbate renal damage in AngII-induced hypertension in SS rats maintained on a 0.4% NaCl diet, similar to the results observed with a salt stimulus in SS rats.

http://ift.tt/2hWDZSs

Tonic aortic depressor nerve stimulation does not impede baroreflex dynamic characteristics concomitantly mediated by the stimulated nerve

Although electrical activation of the carotid sinus baroreflex (baroreflex activation therapy) is being explored as a device therapy for resistant hypertension, possible effects on baroreflex dynamic characteristics of interaction between electrical stimulation and pressure inputs are not fully elucidated. To examine whether the electrical stimulation of the baroreceptor afferent nerve impedes normal short-term arterial pressure (AP) regulation mediated by the stimulated nerve, we electrically stimulated the right aortic depressor nerve (ADN) while estimating the baroreflex dynamic characteristics by imposing pressure inputs to the isolated baroreceptor region of the right ADN in nine anesthetized rats. A Gaussian white noise signal with a mean of 120 mmHg and standard deviation of 20 mmHg was used for the pressure perturbation. A tonic ADN stimulation (2 or 5 Hz, 10 V, 0.1-ms pulse width) decreased mean sympathetic nerve activity (367.0 ± 70.9 vs. 247.3 ± 47.2 arbitrary units, P < 0.01) and mean AP (98.4 ± 7.8 vs. 89.2 ± 4.5 mmHg, P < 0.01) during dynamic pressure perturbation. The ADN stimulation did not affect the slope of dynamic gain in the neural arc transfer function from pressure perturbation to sympathetic nerve activity (16.9 ± 1.0 vs. 14.7 ± 1.6 dB/decade, not significant). These results indicate that electrical stimulation of the baroreceptor afferent nerve does not significantly impede the dynamic characteristics of the arterial baroreflex concomitantly mediated by the stimulated nerve. Short-term AP regulation by the arterial baroreflex may be preserved during the baroreflex activation therapy.

http://ift.tt/2AnlH3L

Arsenic Exposure Induces Glucose Intolerance and Alters Global Energy Metabolism

Environmental pollutants acting as endocrine disrupting chemicals (EDCs) are recognized as potential contributors to metabolic disease pathogenesis. One such pollutant, arsenic, contaminates the drinking water of approximately 100 million people globally and has been associated with insulin resistance and diabetes in epidemiological studies. Despite these observations, the precise metabolic derangements induced by arsenic remain incompletely characterized. In the present study, arsenic's impact on in vivo metabolic physiology was examined in 8 week old male C57BL/6J mice exposed to 50 mg/L inorganic arsenite in their drinking water for 8 weeks. Glucose metabolism was assessed via in vivo metabolic testing, and feeding behavior was analyzed using indirect calorimetry in metabolic cages. Pancreatic islet composition was assessed via immunofluorescence microscopy. Arsenic-exposed mice exhibited impaired glucose tolerance as compared to controls; however, no difference in peripheral insulin resistance was noted between groups. Instead, early insulin release during glucose challenge was attenuated relative to the rise in glycemia. Despite decreased insulin secretion, pancreatic β­cell mass was not altered, suggesting that arsenic primarily disrupts β­cell function. Finally, metabolic cage analyses revealed that arsenic exposure induced novel alterations in the diurnal rhythm of food intake and energy metabolism. Taken together, these data suggest that arsenic exposure impairs glucose tolerance through functional impairments in insulin secretion from β­cells rather than by augmenting peripheral insulin resistance. Further elucidation of the mechanisms underlying arsenic-induced behavioral and β­cell-specific metabolic disruptions will inform future intervention strategies to address this ubiquitous environmental contaminant and novel diabetes risk factor.

http://ift.tt/2hWDQhS

Viscerosensory input drives angiotensin II type 1A receptor expressing neurons in the solitary tract nucleus.

Homeostatic regulation of visceral organ function requires integrated processing of neural and neurohormonal sensory signals. The nucleus of the solitary tract (NTS) is the primary sensory nucleus for cranial visceral sensory afferents. Angiotensin II (Ang II) is known to modulate peripheral visceral reflexes, in part, by activating Ang II type 1A receptors (AT_1AR) in the NTS. AT_1AR-expressing NTS neurons occur throughout the NTS with a defined sub-nuclear distribution and most of these neurons are depolarized by Ang II. In this study we determined whether AT_1AR-expressing NTS neurons receive direct visceral sensory input, and whether this input is modulated by Ang II. Using AT_1AR-GFP mice to make targeted whole cell recordings from AT_1AR-expressing NTS neurons, we demonstrate that two thirds (37 of 56) of AT_1AR-expressing neurons receive direct excitatory, visceral sensory input. In half of the neurons tested (4 of 8) the excitatory visceral sensory input was significantly reduced by application of the transient receptor potential vallinoid type 1 receptor agonist, capsaicin, indicating AT_1AR-expressing neurons can receive either C or A-fibre mediated input. Application of Ang II to a subset of second order AT_1AR-expressing neurons did not affect spontaneous, evoked or asynchronous glutamate release from visceral sensory afferents. Thus it is unlikely that AT_1AR-expressing viscerosensory neurons terminate on AT_1AR-expressing NTS neurons. Our data suggest that Ang II is likely to modulate multiple visceral sensory modalities by altering the excitability of second order AT_1AR-expressing NTS neurons.

http://ift.tt/2AlsWcw

Th17 cells contribute to pulmonary fibrosis and inflammation during chronic kidney disease progression following acute ischemia

Acute kidney injury (AKI) is associated with high mortality rates and predisposes development of chronic kidney disease (CKD). Distant organ damage, particularly in the lung, may contribute to mortality in AKI patients. Animal models of AKI demonstrate an increase in pulmonary infiltration of lymphocytes and reveal an acute compromise of lung function, but the chronic effects of AKI on pulmonary inflammation are unknown. We hypothesized that in response to renal I/R, there is a persistent systemic increase in Th17 cells with potential effects on pulmonary structure and function. Renal ischemia/reperfusion (I/R) injury was performed on rats and CKD progression was hastened by unilateral nephrectomy and exposure to 4.0% sodium diet between 35-63 days post-I/R. Th17 cells in peripheral blood showed a progressive increase up to 63 days following recovery from I/R injury. Infiltration of leukocytes including Th17 cells was also elevated in bronchiolar lavage (BAL) fluid 7 days following I/R and remained elevated for up to 63 days. Lung histology demonstrated an increase in alveolar cellularity and a significant increase in picrosirius red staining. Suppression of lymphocytes with mycophenolate mofetil (MMF) or an IL-17 antagonist significantly reduced Th17 cell infiltration and fibrosis in lung. In addition, tracheal smooth muscle contraction to acetylcholine was significantly enhanced 63-days following I/R relative to sham-operated controls. These data suggest that AKI is associated with a persistent increase in circulating and lung Th17 cells which may promote pulmonary fibrosis and the potential alteration in airway contractility.

http://ift.tt/2AlsNG0

Complement activation via a C3a receptor pathway alters CD4+ T lymphocytes and mediates lung cancer progression

The complement cascade is a part of the innate immune system which acts primarily to remove pathogens and injured cells. However, complement activation is also peculiarly associated with tumor progression. Here we report mechanistic insights into this association in multiple immunocompetent orthotopic models of lung cancer. After tumor engraftment, we observed systemic activation of the complement cascade as reflected by elevated levels of the key regulator C3a. Notably, growth of primary tumors and metastases was both strongly inhibited in C3-deficient mice (C3-/- mice), with tumors undetectable in many subjects. Growth inhibition was associated with increased numbers of IFNγ+/TNFα+/IL-10+ CD4+ and CD8+ T cells. Immunodepletion of CD4+ but not CD8+ T cells in tumor-bearing subjects reversed the inhibitory effects of C3 deletion. Similarly, antagonists of the C3a or C5a receptors inhibited tumor growth. Investigations using multiple tumor cell lines in the orthotopic model suggested the involvement of a C3/C3 receptor autocrine signaling loop in regulating tumor growth. Overall, our findings offer functional evidence that complement activation serves as a critical immunomodulator in lung cancer progression, acting to drive immune escape via a C3/C5-dependent pathway.

http://ift.tt/2At8bfE

Oncolytic virotherapy blockade by microglia and macrophages requires STAT1/3

The first oncolytic virotherapy employing HSV-1 (oHSV-1) was approved recently by the FDA to treat cancer, but further improvements in efficacy are needed to eradicate challenging refractory tumors such as glioblastomas (GBM). Microglia/macrophages comprising ~40% of a GBM tumor may limit virotherapeutic efficacy. Here we show these cells suppress oHSV-1 growth in gliomas by internalizing the virus through phagocytosis. Internalized virus remained capable of expressing reporter genes while viral replication was blocked. Macrophage/microglia formed a nonpermissive OV barrier, preventing dissemination of oHSV-1 in the glioma mass. The deficiency in viral replication in microglial cells was associated with silencing of particular viral genes. Phosphorylation of STAT1/3 was determined to be responsible for suppressing oHSV-1 replication in macrophages/microglia. Treatment with the oxindole/imidazole derivative C16 rescued oHSV-1 replication in microglia/macrophages by inhibiting STAT1/3 activity. In the U87 xenograft model of GBM, C16 treatment overcame the microglia/macrophage barrier, thereby facilitating tumor regression without causing a spread of the virus to normal organs. Collectively, our results suggest a strategy to relieve a STAT1/3 dependent therapeutic barrier and enhance oHSV-1 oncolytic activity in GBM.

http://ift.tt/2yidNrF

IDO Immune Status after Chemoradiation May Predict Survival in Lung Cancer Patients

Host immunity influences the impact of radiotherapy (RT) in cancer but mechanistic connections remain obscure. In this study, we investigated the relationship of indoleamine 2,3-dioxygenase (IDO) systemic activity on clinical outcomes in RT-treated non-small cell lung cancer (NSCLC). IDO-mediated production of kynurenine and the kynurenine:tryptophan ratio in patient blood serum were determined for stage III NSCLC patients at times before, during and after RT administration and then correlated to overall survival (OS), progression-free survival and disease progression rate in patients. We found the impact of RT on these serum IDO markers to be heterogeneous in patients. On average, kynurenine:tryptophan ratios were reduced during RT but restored after RT. Notably, both baseline levels of kynurenine:tryptophan and changes in the levels of kynurenine after RT were significantly associated with OS. When combined, favorable change and favorable baseline corresponded with very long-term OS (median OS was not reached after 57 months median follow-up). Favorable change combined with unfavorable baseline still corresponded with a lack of distant metastases. Our results suggest that RT alters IDO-mediated immune status in NSCLC patients and that changes in this serum biomarker may be useful to predict outcomes and perhaps personalize RT dosage to improve survival.

http://ift.tt/2AvsV6m

Concordance in BRAF V600E status over time in malignant melanoma and corresponding metastases

Abstract

Aims

The present study analysed the usability of an immunohistochemical (IHC) analysis compared to a frequently used mutation detection analysis and examined the extent of intra- and inter-tumour heterogeneity of BRAF V600E in primary tumours and their corresponding metastases. In the development of inter-tumour heterogeneity between the primary tumour and the corresponding metastases, time as a factor was also investigated.

Methods

In total, 227 samples from 224 melanoma patients were analysed using both the Cobas^® 4800 BRAF V600 Mutation test and IHC anti-BRAF V600E staining. In 82 primary tumours and 224 corresponding metastases, the extent of inter- and intra-tumour heterogeneity was investigated using IHC staining.

Results

In 15 cases, disagreement between IHC analysis and the Cobas test was seen. In all but one of the examined patients, homogeneity between the primary tumour and the corresponding metastasis was found. Except for this one case, no heterogeneity developed over longer periods.

Conclusion

IHC analysis can be safely used as a BRAF pre-therapy screening tool, and no additional test is needed when staining is positive. However, if stains are negative, additional tests are essential for detection of other BRAF mutations. We suggest that using primary melanoma tissues is just as safe as using metastatic tissue for detection of BRAF V600E, since BRAF inter-tumour heterogeneity is extremely rare. In addition, the time between diagnosis of the primary tumour and diagnosis of the corresponding metastasis seems not to increase the risk of inter-tumour heterogeneity

This article is protected by copyright. All rights reserved.

http://ift.tt/2je4WV7

Biphasic Papillary Renal Cell Carcinoma Is a Rare Morphologic Variant with Frequent Multifocality: A Study of 28 Cases

Abstract

Aims

To further characterize biphasic squamoid renal cell carcinoma (RCC), a recently proposed variant of papillary RCC.

Methods and results

We identified 28 tumors from multiple institutions. They typically demonstrated two cell populations - larger cells with eosinophilic cytoplasm and higher-grade nuclei, surrounded by smaller, amphophilic cells with scanty cytoplasm. The dual morphology was variable (median 72.5% of tumor, range 5-100%); emperipolesis was found in all cases. Male-to-female ratio was 2:1, median age 55 years (range 39-86). Median tumor size was 2 cm (range 0.9-6.5). Pathologic stage pT1a was found in 21 cases, pT1b in 3, pT3a and pT3b in 1 patient each (2 not available). Multifocality was found in 32%: multifocal biphasic RCC in 1, biphasic + papillary RCC in 2, biphasic + clear cell RCC in 3, biphasic + low-grade urothelial carcinoma of renal pelvis in 1, and biphasic + Birt-Hogg-Dubé syndrome in 1 case. Positive immunostains included: PAX8, CK7, AMACR, EMA, and vimentin. Cyclin D1 was expressed only in the larger cells. Ki67 index was higher in the larger cells (median 5% vs. ≤1%). Negative stains included: CA9, CD117, GATA3, WT1, CK5/6 and CK20; CD10 and 34βE12 were variably expressed. Gains of chromosomes 7 and 17 were found in 2 evaluated cases. Follow-up was available for 23 patients (median 24 months, range 1-244): 19 were alive without disease, 1 was alive with recurrence, 1 died of disease (2 died of other causes).

Conclusions

Biphasic papillary RCC is a rare variant of papillary RCC, which is often multifocal.

This article is protected by copyright. All rights reserved.

http://ift.tt/2hqfT5z

Treating Recurrent Glioma with Toca 511 [News in Brief]

Selectively replicating retroviral vector delivers high local concentrations of 5-FU directly to brain tumors.

http://ift.tt/2ztDOG1

Papillary Adenocarcinoma in a Gastric Duplication Cyst

Abstract

Gastric duplication cysts are rare and mostly present in the first year of life. In adulthood presentation is in the form of obstruction, ulceration, bleeding, fistulization etc. Malignancy is extremely rare with only 12 cases reported to date. We came across a gastric duplication cyst with papillary adenocarcinoma in a 63 year old man. He underwent cyst excision with radical subtotal gastrectomy. The awareness of such a condition made it possible for us to have a suspicion of malignancy preoperatively based on imaging and thus a radical surgery was performed. High index of suspicion is necessary to diagnose this condition preoperatively on CT scan. Literature review revealed that this is the first case to be reported from India.

http://ift.tt/2zrD3iB

A ravenous defense: canonical and non-canonical autophagy in immunity

Payel Sil | Ginger Muse | Jennifer Martinez

http://ift.tt/2jclltl

Correction to: Relative abundance of β-thalassemia-related mutations in southern China correlates with geographical coordinates

Abstract

Figure 1c. is with numeric error. The error can not result in any change of discussion and conclusion. The proper figures corresponding to Fig 1c are in supplement file, see figure 5 and 6.

http://ift.tt/2Awpfld

Compounded Glutamine, Arginine, and Carnitine Product for Injection by United Pharmacy: Compounding Risk Alert - FDA Investigates Two Adverse Events

Audience: Health Professionals ISSUE: FDA received an adverse event report stating that two patients developed what is described in the report as tissue erosion at the injection site following the administration of an injectable glutamine, arginine,...

http://ift.tt/2yjjeXp

Mass Administration of Ivermectin in Areas Where Loa loa Is Endemic

The 2015 Nobel Prize in Medicine was shared in part by the discoverers of ivermectin. Donated tablets of ivermectin have been distributed in Africa since 1988 through mass drug administration programs for onchocerciasis, or river blindness (caused by Onchocerca volvulus), and since 2000 for…

http://ift.tt/2m8bYvE

A Test-and-Not-Treat Strategy for Onchocerciasis in Loa loa–Endemic Areas

Mass drug administration with regimens containing ivermectin is the main strategy for the elimination of lymphatic filariasis and onchocerciasis. Although ivermectin is generally safe, the distribution of the drug has been associated with serious adverse events in central African countries. Since…

http://ift.tt/2yJfP8B

Health Care Professionals and Law Enforcement

Health care professionals generally have a respectful, sometimes even friendly, attitude toward law enforcement. We may feel we're on the same team as the police when we're treating victims of crime, and police may be called to protect us from people who seek to harm us in the hospital. Some health…

http://ift.tt/2m674PV

The Promise, Growth, and Reality of Mobile Health — Another Data-free Zone

The use of mobile communication technologies to improve the health of individuals and populations — dubbed "mobile health," or "mHealth" — has grown dramatically since 2008, when the term mHealth became widely used. The excitement over the use of mHealth technology especially in low- and…

http://ift.tt/2yKGLVl

Crestline awarded $23.7 million contract for BCEHS ambulances

SASKATOON, Canada — Crestline Coach, a global leader in ambulance and specialty vehicle manufacturing, has secured a multi-year deal with BC Emergency Health Services (BCEHS). Manufacturing is currently underway at Crestline's production headquarters, situated in Saskatoon, Saskatchewan, with delivery scheduled to begin early 2018. BCEHS is a long-standing customer of Crestline Coach, purchasing ...

http://ift.tt/2Awe8bQ

Compounded Glutamine, Arginine, and Carnitine Product for Injection by United Pharmacy: Compounding Risk Alert - FDA Investigates Two Adverse Events

Audience: Health Professionals ISSUE: FDA received an adverse event report stating that two patients developed what is described in the report as tissue erosion at the injection site following the administration of an injectable glutamine, arginine,...

http://ift.tt/2yjjeXp

Benign recurrent intrahepatic cholestasis (BRIC)-like episode associated with ATP8B1 variation underlying protracted cholestatic course of acute hepatitis E virus infection

http://ift.tt/2yjfcOO

Effects of miR-340 on hepatocellular carcinoma by targeting the DcR3 gene

In hepatocellular carcinoma (HCC), miR-340 plays a vital role in the regulation of tumor occurrence and deterioration, while DcR3 gene is involved in cancer cell proliferation and apoptosis. This study analyzed miR-340 in the serum of patients with HCC and healthy controls. Then, miR-340, DcR3, TGF-β1 and Smad2 expression were measured in HCC tissues and adjacent parts. Relationship between miR-340 and DcR3 was verified. Effects of miR-340 on human HepG2 cell proliferation and apoptosis were explored.

http://ift.tt/2AvMuvt

The discovery of the “Etruscan intestine”

Everyone knows the "Liver of the Etruscans", a bronze dating back to the end of the 2nd century B.C. used by the haruspex-priests to divine.

http://ift.tt/2ykhcX7

An unusual primary omental tumor: mixed germ cell tumor

Primary tumors of the greater omentum are rare. Mixed germ-cell tumor, which is derived from germ cells, occurs mainly in gonad of adolescents and young adults. In the present case, we report a 58-year-old woman, who was admitted to the hospital because of abdominal discomfort. Magnetic resonance imaging revealed a large mass in the left lower quadrant. Pertinent laboratory tests were within normal limits except for a rise in serum alfa-fetoprotein. During laparotomy, a solitary mass arising from the greater omentum was confirmed.

http://ift.tt/2AvMn31

International variations in primary care physician consultation time: a systematic review of 67 countries

Objective

To describe the average primary care physician consultation length in economically developed and low-income/middle-income countries, and to examine the relationship between consultation length and organisational-level economic, and health outcomes.

Design and outcome measures

This is a systematic review of published and grey literature in English, Chinese, Japanese, Spanish, Portuguese and Russian languages from 1946 to 2016, for articles reporting on primary care physician consultation lengths. Data were extracted and analysed for quality, and linear regression models were constructed to examine the relationship between consultation length and health service outcomes.

Results

One hundred and seventy nine studies were identified from 111 publications covering 28 570 712 consultations in 67 countries. Average consultation length differed across the world, ranging from 48 s in Bangladesh to 22.5 min in Sweden. We found that 18 countries representing about 50% of the global population spend 5 min or less with their primary care physicians. We also found significant associations between consultation length and healthcare spending per capita, admissions to hospital with ambulatory sensitive conditions such as diabetes, primary care physician density, physician efficiency and physician satisfaction.

Conclusion

There are international variations in consultation length, and it is concerning that a large proportion of the global population have only a few minutes with their primary care physicians. Such a short consultation length is likely to adversely affect patient healthcare and physician workload and stress.

http://ift.tt/2zGdon7

Identifying Human Phenotype Terms by Combining Machine Learning and Validation Rules

Named-Entity Recognition is commonly used to identify biological entities such as proteins, genes, and chemical compounds found in scientific articles. The Human Phenotype Ontology (HPO) is an ontology that provides a standardized vocabulary for phenotypic abnormalities found in human diseases. This article presents the Identifying Human Phenotypes (IHP) system, tuned to recognize HPO entities in unstructured text. IHP uses Stanford CoreNLP for text processing and applies Conditional Random Fields trained with a rich feature set, which includes linguistic, orthographic, morphologic, lexical, and context features created for the machine learning-based classifier. However, the main novelty of IHP is its validation step based on a set of carefully crafted manual rules, such as the negative connotation analysis, that combined with a dictionary can filter incorrectly identified entities, find missed entities, and combine adjacent entities. The performance of IHP was evaluated using the recently published HPO Gold Standardized Corpora (GSC), where the system Bio-LarK CR obtained the best -measure of 0.56. IHP achieved an -measure of 0.65 on the GSC. Due to inconsistencies found in the GSC, an extended version of the GSC was created, adding 881 entities and modifying 4 entities. IHP achieved an -measure of 0.863 on the new GSC.

http://ift.tt/2zGuJfU

Prostate Cancer: From Genomics to the Whole Body and Beyond

http://ift.tt/2zp8RVz

Protein overexpression and gene amplification of cellular mesenchymal-epithelial transition factor is associated with poor prognosis in micropapillary predominant subtype pulmonary adenocarcinoma

Micropapillary predominant subtype pulmonary adenocarcinoma (MPPAC) is a subtype of lung cancer with poor prognosis. Cellular mesenchymal-epithelial transition factor (c-MET) is a promising pharmaceutic target found to be associated with the survival of patients with pulmonary adenocarcinoma (PAC). In this study, we aimed to analyze c-MET protein overexpression and gene amplification in MPPAC samples and to elucidate their relationship with the clinicopathological characteristics of the patients.

http://ift.tt/2jaowSn

Delineation of neck clinical target volume specific to nasopharyngeal carcinoma based on lymph node distribution and the international consensus guidelines

Neck node distribution probability maps and curves for NPC were established based on 10651 nodes from 956 patients. Relationships between node distribution and international consensus guidelines for delineation of neck node levels were analyzed. Our findings demonstrate that the majority of node levels in the 2013 updated consensus guidelines are comprehensive and applicable for NPC. We propose a new level VIIc to include medial group of retropharyngeal LNs, recommend moderate extended boundaries for levels Vb and VIIa, and suggest that boundaries for levels Ib, II, IV and Vc might be reduced.

http://ift.tt/2zuckjB

Effects of Proton Center Closure on Pediatric Case Volume and Resident Education at an Academic Cancer Center

Changes in radiation oncology infrastructure influence referral/practice patterns and resident educational experiences. This study aimed to analyze effects of closure of an academic proton treatment center (PTC) on pediatric case volume, distribution, and resident education. We demonstrate a sharp decrease in overall pediatric cases and potentially curable CNS tumors treated at our center following PTC closure. Our findings raise important questions regarding resident training in pediatric radiation oncology as these cases become concentrated at specialized centers.

http://ift.tt/2iFEjoe

Czech version of the Patient Dignity Inventory: Translation and Validation in Incurable Patients

The Patient Dignity Inventory (PDI) is a valid, reliable screening tool to assess a range of issues that have been reported to affect the sense of dignity in patients with life-limiting conditions.

http://ift.tt/2zIl20q

Shared decision making in home hospice nursing visits: A qualitative study

Shared decisions between health care providers and patients and families are replacing the traditional physician-driven plans of care. Hospice philosophy recognizes the patient and family as a unit of care and embraces their role in decision making.

http://ift.tt/2zsRxib

Increased Systemic Antibiotic Use And Clostridium difficile Infection Among Outpatients With Irritable Bowel Syndrome

http://ift.tt/2jczNBE

Budesonide in autoimmune hepatitis: the right drug at the right time for the right patient

http://ift.tt/2Auy26P

A pilot study of endoscopically inserted biodegradable biliary stents in the treatment of benign biliary strictures and cystic duct leaks

Self-expanding biodegradable biliary stents (BDBSs) have recently become available for use in endoscopic retrograde cholangiography (ERC). The aim was to evaluate the effectiveness and safety of novel BDBS in iatrogenic cystic duct leaks and benign biliary strictures (BBSs).

http://ift.tt/2AlgNnQ

Liquid Biopsy: Using DNA in Blood to Detect, Track, and Treat Cancer

Research studies show tests that analyze tumor DNA in blood, called liquid biopsies, may help detect cancer early, guide precision cancer treatment, and tracking treatment response.

http://ift.tt/2zojEPW

Neuroprotective effect of neuroserpin in non-tPA-induced intracerebral hemorrhage mouse models

The neuroprotective effects of neuroserpin (NSP) have been well documented in both patients and animal models with cerebral ischemia; however, have never been investigated in hemorrhagic stroke. The aim of thi...

http://ift.tt/2yIyXTZ

Cardiac Rhabdomyomas in Tuberous Sclerosis Complex

A male infant born at 31 weeks' of gestation and weighing 1700 grams presented with sudden cardiac arrest at the birth hospital. The infant was transferred to the neonatal intensive care unit and cardiology was consulted. Echocardiogram revealed a large echogenic and homogeneous mass in the interventricular septum (Figure, A, B). The infant had poor biventricular function and severe hemodynamic instability complicated by a second cardiac arrest. Cardiothoracic surgery was consulted, but the massive tumor was considered not amenable for surgery.

http://ift.tt/2zsOtk4

PVL overexpression due to genomic rearrangements and mutations in the S. aureus reference strain ATCC25923

ATCC25923 is a Staphylococcus aureus strain that is positive for the Panton Valentin leukocidin. It has been used for decades as reference strain. We observed that two separately maintained clones of ATCC25923 ("...

http://ift.tt/2znrhGz

Management of X-linked adrenoleukodystrophy in Morocco: actual situation

X-linked adrenoleukodystrophy is a neurodegenerative disorder caused by mutations in the ABCD1 gene. Adrenomyeloneuropathy and childhood cerebral Adrenoleukodystrophy are the most common phenotypes. This paper fo...

http://ift.tt/2zIfZ0b

Phage typing or CRISPR typing for epidemiological surveillance of Salmonella Typhimurium?

Salmonella Typhimurium is the most dominant Salmonella serovar around the world. It is associated with foodborne gastroenteritis outbreaks but has recently been associated with invasiv...

http://ift.tt/2zoTVHe

Genetic model misspecification in genetic association studies

The underlying model of the genetic determinant of a trait is generally not known with certainty a priori. Hence, in genetic association studies, a dominant model might be erroneously modelled as additive, an ...

http://ift.tt/2zHL57T

Use of tuberculin skin test for assessment of immune recovery among previously malnourished children in Ethiopia

To compare levels of immunity in children recovering from severe acute malnutrition (cases) against those of community controls (controls).

http://ift.tt/2zmtoKF

EMS and evidence-based medicine solutions

By Guillermo Fuentes The term "evidence-based practice" has been used in EMS for more than a decade. The reality is, as a profession, we fail to understand what implementing an evidence-based practice actually means. One of the most influential thinkers on the subject, the late physician David Sackett, defined evidence-based medicine as "the conscientious, explicit and judicious use ...

http://ift.tt/2yIEEBu

Association Between Gestational Diabetes and Incident Maternal CKD: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Gestational diabetes mellitus (GDM) is associated with increased risk for diabetes mellitus, metabolic syndrome, and cardiovascular disease. We evaluated whether GDM is associated with incident chronic kidney disease (CKD), controlling for prepregnancy risk factors for both conditions.

http://ift.tt/2AocuYG

Association of Citizenship Status With Kidney Transplantation in Medicaid Patients

Although individuals classified as nonresident aliens, including undocumented immigrants, are entitled to receive emergency dialysis in the United States regardless of their ability to pay, most states do not provide them with subsidized care for maintenance dialysis or kidney transplantation. We explored whether nonresident aliens have similar outcomes to US citizens after receiving kidney transplants covered by Medicaid, a joint federal and state health insurance program.

http://ift.tt/2hU5dcn

Psychometric Properties of the Kidney Disease Quality of Life 36-Item Short-Form Survey (KDQOL-36) in the United States

The Centers for Medicare & Medicaid Services require that dialysis patients' health-related quality of life be assessed annually. The primary instrument used for this purpose is the Kidney Disease Quality of Life 36-Item Short-Form Survey (KDQOL-36), which includes the SF-12 as its generic core and 3 kidney disease–targeted scales: Burden of Kidney Disease, Symptoms and Problems of Kidney Disease, and Effects of Kidney Disease. Despite its broad use, there has been limited evaluation of KDQOL-36's psychometric properties.

http://ift.tt/2AocmZc

Liquid Biopsy: Using DNA in Blood to Detect, Track, and Treat Cancer

Research studies show tests that analyze tumor DNA in blood, called liquid biopsies, may help detect cancer early, guide precision cancer treatment, and tracking treatment response.

http://ift.tt/2jbwYAI

Effects of combined application of nitrogen fertilizer and biochar on the nitrification and ammonia oxidizers in an intensive vegetable soil

Soil amended with single biochar or nitrogen (N) fertilizer has frequently been reported to alter soil nitrification process due to its impact on soil properties. However, little is known about the dynamic re...

http://ift.tt/2Alb3dM

Admission of tetanus patients to the ICU: a retrospective multicentre study

An extended course of tetanus (up to 6 weeks) requiring ICU admission and protracted mechanical ventilation (MV) may have a significant impact on short- and long-term survival. The subject is noteworthy and d...

http://ift.tt/2hTOCWj

Venovenous extracorporeal membrane oxygenation devices-related colonisations and infections

Nosocomial infections occurring during extracorporeal membrane oxygenation (ECMO) support have already been reported, but few studied infections directly related to ECMO devices. This study aims to evaluate t...

http://ift.tt/2zpGYwC

7 products to help you pass paramedic school

Preparing for paramedic school is more than recalling previous on-the-job experience. Consider these tools to help you with your coursework and prepare you to become a certified paramedic.

http://ift.tt/2AmoHxp

Composite intestinal adenoma-microcarcinoid in the colon and rectum: a case series and historical review

Composite intestinal adenoma-microcarcinoid (CIAM) is a rare colorectal lesion that mostly comprises a conventional adenomatous component with a minute proportion of neuroendocrine (NE) component. Although mic...

http://ift.tt/2zs3ipe

An Array-based Comparative Genomic Hybridization Platform for Efficient Detection of Copy Number Variations in Fast Neutron-induced Medicago truncatula Mutants

This protocol provides experimental steps and information about reagents, equipment, and analysis tools for researchers who are interested in carrying out whole genome array-based comparative genomic hybridization (CGH) analysis of copy number variations in plants.

http://ift.tt/2hdEarT

Ohio EMS agency offers scholarships for students in EMT program

By Nikki Blankenship The Portsmouth Daily Times PORTSMOUTH, Ohio — Portsmouth Ambulance is once again offering their scholarship program for individuals interested in exploring a career as an emergency medical technician (EMT). Last semester, Portsmouth Ambulance worked with Shawnee State University (SSU) to offer seven scholarships of $700 each, plus books in order to help combat emergency medical ...

http://ift.tt/2AoFPSZ

Pregnancy nutrition knowledge and experiences of pregnant women and antenatal care clinicians: A mixed methods approach

Publication date: Available online 7 November 2017
Source:Women and Birth
Author(s): Amelia Lee, Michelle Newton, Jessica Radcliffe, Regina Belski
BackgroundDietary intake of pregnant women do not appear to meet the dietary recommendations. Nutrition knowledge and practices of pregnant women and their antenatal care clinicians are factors that may be influential on dietary intakes of pregnant women.AimTo assess and compare pregnancy nutrition recommendation knowledge and to explore how nutrition knowledge impacts on food choices in pregnant women and nutrition education practices of antenatal care providers.MethodsAn explanatory sequential research mixed methods study design was applied. All participants were recruited from a metropolitan maternity hospital in Melbourne, Australia. The first phase assessed pregnancy nutrition knowledge and sources of nutrition information using a questionnaire (n=202) then followed semi-structured interviews with women and clinicians (n=31).FindingsThe clinicians obtained significantly higher nutrition scores than compared to women, however, nutrition knowledge gaps were highlighted for both women and clinicians. Women reported receiving limited nutrition advice, a reflection of the clinicians reporting they provided limited nutrition advice.ConclusionA key challenge for women adhering to dietary recommendations was having inadequate knowledge of the dietary recommendations and receiving limited information from their care providers. Similarly, as well as time constraints, limited nutrition knowledge and a lack of nutrition training impacted on the capacity of clinicians to provide adequate nutrition education.



http://ift.tt/2yIfD9p