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Παρασκευή 1 Φεβρουαρίου 2019

Functional Results and Quality of Life Following Magnetic Anal Sphincter Augmentation in Severely Incontinent Patients

imageObjective: Magnetic anal sphincter augmentation is a novel surgical option in the treatment of severe fecal incontinence. This study aimed to analyze functional results, quality of life, and satisfaction after implantation in the mid-term, and to identify factors associated with success of this new treatment. Methods: All patients, who underwent magnetic anal sphincter augmentation procedure at a single center between December 2008 and January 2016, were consecutively included. Symptom severity [Cleveland Clinic Incontinence Score (CCIS)], quality of life [Fecal-Incontinence Quality of Life Questionnaire (FIQL)], bowel diary data, and patients' satisfaction were assessed before and after implantation. Results: Forty-five patients (43 female), mean (s.d.) age 66.82 (±10.07), were followed for a median of 36 months (range 6–84). Two patients were explanted and 1 lost to follow-up. On a 3-week diary, major leakage rate significantly improved as did CCIS and FIQL. No significant difference was seen for flatus and minor leaks. Postoperative decrease of CCIS by ≥5.5 points correlated best with satisfaction, expressed by 22 patients (48% in intention-to-treat analysis). An independent predictive factor for success after implantation was no previous fecal incontinence surgical treatment. Conclusions: Satisfaction, functional, and quality of life outcomes improve significantly following magnetic anal sphincter augmentation.

http://bit.ly/2SJ13EP

Differential expression of S1P receptor subtypes in human bladder transitional cell carcinoma

Abstract

Purpose

Sphingosine 1 phosphate (S1P), S1P receptors (S1PRs) and their signaling pathways play an important role in the fate of cancer cells. The expression pattern of S1PR subtypes (S1PR1–S1PR5) may alter in cancer development stages, depending on the origin and the pathologic features of tumors. The present study aimed to examine the relationship between plasma S1P levels and the expression of S1PR subtypes in bladder tumors.

Methods/patients

These changes were evaluated in terms of the pathologic grades and stages of human bladder cancer samples. For this, tumor biopsies from 41 new bladder cancer patients as well as 26 normal-looking bladder tissues were collected and processed for immunohistochemistry (IHC) and quantitative real-time RT-PCR of S1PR subtypes. Plasma S1P level was measured using liquid chromatography–tandem mass spectrometry (LC–MS/MS).

Results

The results show that tissue S1PR1, S1PR2 and S1PR3 are over-expressed in all tumors regardless of their pathological grade (~ 3, ~ 6 and ~ 104 folds, respectively). These results were corroborated by IHC data showing accumulation of S1PR subtypes 1 and 2 in the tissues. Plasma S1P in the plasma samples from patients was in the range of control samples (Controls; 256 ± 47; patients, 270 ± 41).

Conclusions

Overexpression of S1PR1, S1PR2 and S1PR3 in bladder tumor biopsies which were corroborated with the pathological grades and stages may suggest that S1PR profile in tumor biopsies is a promising marker in the diagnosis of bladder carcinoma.



http://bit.ly/2t3Odpr

Promoting Brain Repair and Regeneration After Stroke: a Plea for Cell-Based Therapies

Abstract

Purpose of Review

After decades of hype, cell-based therapies are emerging into the clinical arena for the purposes of promoting recovery after stroke. In this review, we discuss the most recent science behind the role of cell-based therapies in ischemic stroke and the efforts to translate these therapies into human clinical trials.

Recent Findings

Preclinical data support numerous beneficial effects of cell-based therapies in both small and large animal models of ischemic stroke. These benefits are driven by multifaceted mechanisms promoting brain repair through immunomodulation, trophic support, circuit reorganization, and cell replacement.

Summary

Cell-based therapies offer tremendous potential for improving outcomes after stroke through multimodal support of brain repair. Based on recent clinical trials, cell-based therapies appear both feasible and safe in all phases of stroke. Ongoing translational research and clinical trials will further refine these therapies and have the potential to transform the approach to stroke recovery and rehabilitation.



http://bit.ly/2WxKzlj

Radiotherapy for parotid malignancies: patterns of care and impact on overall survival

Abstract

Introduction

Parotid tumors are rare, and no clinical trial data exists to guide postoperative radiation therapy (PORT) usage. We sought to determine the impact of PORT on the overall survival (OS) of patients with parotid malignancies.

Methods

Patient data was queried from the National Cancer Database. Patients with surgical resection of parotid gland carcinomas from 2004 to 2012 were analyzed. Kaplan-Meier and Cox proportional hazards were used to assess OS among those receiving PORT or not. Additionally, variables affecting OS and use of PORT were evaluated.

Results

A total of 12,439 patients were identified for analysis. Increasing T stage, N stage, tumor grade, and positive margin status were predictive of PORT. Survival for patients receiving PORT versus surgery only at 5 and 10 years was 65.5% and 50.3% versus 74.4% and 61.2% for surgery only (p ≤ 0.001). After multivariable adjustment, PORT improved OS (adjusted hazard ratio 0.79, 95% confidence interval 0.70–0.89). In subgroup analysis, PORT provided benefit for certain histologic subtypes and all other patient groups except those with T1 tumors and undifferentiated/anaplastic tumor grades.

Conclusions

Our data suggests that PORT was associated with improved survival. Additionally, some subgroups may receive additional benefit and patients with small (T1), low-grade disease may be able to forgo PORT.



http://bit.ly/2HOiGSx

Telomeres in Interstitial Lung Disease: The Short and the Long of It

Annals of the American Thoracic Society, Volume 16, Issue 2, Page 175-181, February 2019.


http://bit.ly/2HKrCIM

Reducing Chronic Obstructive Pulmonary Disease Hospital Readmissions. An Official American Thoracic Society Workshop Report

Annals of the American Thoracic Society, Volume 16, Issue 2, Page 161-170, February 2019.


http://bit.ly/2t0d9hl

Which Shall I Choose? Lung Transplantation Listing Preference for Individuals with Interstitial Lung Disease and Chronic Obstructive Pulmonary Disease

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Annals of the American Thoracic Society, Volume 16, Issue 2, Page 193-195, February 2019.


http://bit.ly/2HMhlM4

Frailty and Clinical Outcomes in Chronic Obstructive Pulmonary Disease

Annals of the American Thoracic Society, Volume 16, Issue 2, Page 217-224, February 2019.


http://bit.ly/2t3IqjH

Aligning Prescribing Practices with Chronic Obstructive Pulmonary Disease Guidelines: A Sisyphean Struggle?

Annals of the American Thoracic Society, Volume 16, Issue 2, Page 187-188, February 2019.


http://bit.ly/2HKCupK

Financial Incentives Promote Smoking Cessation Directly, Not by Increasing Use of Cessation Aids

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Annals of the American Thoracic Society, Volume 16, Issue 2, Page 280-282, February 2019.


http://bit.ly/2sZzEDn

Clear as Mud: Diagnostic Uncertainty in Acute Respiratory Distress Syndrome

Annals of the American Thoracic Society, Volume 16, Issue 2, Page 197-199, February 2019.


http://bit.ly/2HZ54nN

Blood Collection Technique May Affect QuantiFERON-TB Gold Plus Assay Results

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Annals of the American Thoracic Society, Volume 16, Issue 2, Page 275-276, February 2019.


http://bit.ly/2t2RAwO

Looking at the Definition of Airflow Obstruction through a New Lens: Time for a Change?

Annals of the American Thoracic Society, Volume 16, Issue 2, Page 191-192, February 2019.


http://bit.ly/2HLLBXw

Diffusing Capacity of the Lung for Carbon Monoxide in Mexican/Latino Children. Quality Control and Reference Values

Annals of the American Thoracic Society, Volume 16, Issue 2, Page 240-247, February 2019.


http://bit.ly/2sZZRS7

Discordance between Imaging Modalities in the Evaluation of Chronic Thromboembolic Pulmonary Hypertension: A Combined Experience from Two Academic Medical Centers

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Annals of the American Thoracic Society, Volume 16, Issue 2, Page 277-280, February 2019.


http://bit.ly/2t2RBAS

A Comparison of Global Lung Initiative 2012 with Third National Health and Nutrition Examination Survey Spirometry Reference Values. Implications in Defining Obstruction

Annals of the American Thoracic Society, Volume 16, Issue 2, Page 225-230, February 2019.


http://bit.ly/2HLLuv4

Differences between Patients in Whom Physicians Agree and Disagree about the Diagnosis of Acute Respiratory Distress Syndrome

Annals of the American Thoracic Society, Volume 16, Issue 2, Page 258-264, February 2019.


http://bit.ly/2sYLqhb

An Aliasing Polysomnographic Finding

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Annals of the American Thoracic Society, Volume 16, Issue 2, Page 268-270, February 2019.


http://bit.ly/2HVVvWi

Procedure Preference and Intention-to-Treat Outcomes after Listing for Lung Transplantation among U.S. Adults. A Cohort Study

Annals of the American Thoracic Society, Volume 16, Issue 2, Page 231-239, February 2019.


http://bit.ly/2sZGatw

Evaluating a custom-designed aid to improve communication of genetic results in families with hypertrophic cardiomyopathy: study protocol for a randomised controlled trial

Introduction

Genetic testing for hypertrophic cardiomyopathy (HCM) in the era of genomics brings unique challenges for genetic counselling. The number of genes routinely included in an HCM gene panel has increased markedly, many with minimal if any robust evidence of gene–disease association. Subsequently, there is a greater chance of uncertain genetic findings. The responsibility of communicating this information with at-risk relatives lies with the index case (proband). We have developed a communication aid to assist with the delivery of genetic results to the proband. We have previously shown the aid is feasible and acceptable and have now developed a study protocol for a randomised controlled trial of a genetic counsellor-led intervention incorporating the communication aid.

Methods and analysis

This is a prospective randomised controlled trial. We will investigate the impact of a genetic counsellor-led intervention to return proband genetic results using a custom-designed communication aid. We aim to improve knowledge and empowerment. The primary outcome of this trial is the ability and confidence of the proband to communicate genetic results to at-risk relatives. Secondary outcomes will assess genetic knowledge, satisfaction with services, outcomes from genetic counselling and psychological adaptation to genetic information.

Ethics and dissemination

This study has been approved by and is in strict accordance with the Sydney Local Health District Ethics Review Committee (X16-0030; 22/01/2016; version 1). Results from this trial will be prepared as a manuscript and submitted to peer-reviewed journals for publication as well as submission for presentation at national and international meetings.

Trial registration number

ACTRN12617000706370.



http://bit.ly/2UBc8s4

Nurses 12-hour shifts and missed or delayed vital signs observations on hospital wards: retrospective observational study

Objectives

12-hour shifts worked by nurses on acute hospital wards have been associated with increased rates of missed care reported by nurses. This study aimed to measure the association between nurses working shifts of at least 12 hours and an objective measure of missed care: vital signs observations taken on time according to an acuity-based surveillance protocol.

Design

A retrospective observational study using routinely collected data from March 2012 to March 2015.

Setting

32 general inpatient wards at a large acute hospital in England.

Participants

658 628 nursing shifts nested in 24 069 ward days.

Outcome measures

The rate of daily delayed and missed vital signs observations. We focused on situations where vital signs observations were required at least every 4 hours and measured the number of instances where observations were delayed or missed, per 24-hour period. For each ward and each day, shift patterns were characterised in terms of proportion of care hours per patient day deriving from 'long' shifts (≥12 hours) for both registered nurses and healthcare assistants.

Results

On 99 043 occasions (53%), observations were significantly delayed, and on 81 568 occasions (44%), observations were missed. Observations were more likely to be delayed when a higher proportion of the hours worked by healthcare assistants were part of long shifts (IRR=1.05; 95% CI 1.00 to 1.10). No significant association was found in relation to the proportion of hours registered nurses worked as long shifts.

Conclusion

On days when a higher proportion of hours worked by healthcare assistants are from long shifts, the risk of delaying vital signs observations is higher, suggesting lower job performance. While longer shifts are thought to require fewer staff resources to maintain nurse-to-patient ratios, any benefits may be lost if staff become less productive.



http://bit.ly/2S7MZs3

WHO guidance on mental health training: a systematic review of the progress for non-specialist health workers

Objective

To assess existing literature on the effectiveness of mental health training courses for non-specialist health workers, based on the WHO guidelines (2008).

Design

A systematic review was carried out, complying with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist.

Data sources

After examination of key studies in the literature, a comprehensive search was performed within the following electronic databases on 31 May 2017: PubMed, PsycINFO, CINAHL (using EBSCOHost interface), Cochrane, Web of Science.

Eligibility criteria

Searches were conducted for articles published in English from January 2008 to May 2017, using search terms related to mental health, training, community care and evaluation/outcome, following the Participants, Interventions, Comparators and Outcomes process for evidence-based practice.

Outcomes

Data were collected across the following categories: trainees (number and background), training course (curriculum, teaching method, length), evaluation method (timing of evaluation, collection method and measures assessed) and evaluation outcome (any improvement recorded from baseline). In addition, studies were assessed for their methodological quality using the framework established by Liu et al (2016).

Results

29 studies with relevant training courses met the inclusion criteria. These were implemented across 16 countries since 2008 (over half between 2014 and 2017), with 10 in three high-income countries. Evaluation methods and outcomes showed high variability across studies, with courses assessing trainees' attitude, knowledge, clinical practice, skills, confidence, satisfaction and/or patient outcome. All 29 studies found some improvement after training in at least one area, and 10 studies found this improvement to be significant.

Conclusions

Training non-specialist workers in mental healthcare is an effective strategy to increase global provision and capacity, and improves knowledge, attitude, skill and confidence among health workers, as well as clinical practice and patient outcome. Areas for future focus include the development of standardised evaluation methods and outcomes to allow cross-comparison between studies, and optimisation of course structure.

PROSPERO registration number

CRD42016033269



http://bit.ly/2UDj5sH

Comparative safety of the sodium glucose co-transporter 2 (SGLT2) inhibitors: a systematic review and meta-analysis

Objective

To estimate the association between the use of sodium glucose co-transporter-2 (SGLT2) inhibitors and postmarket harms as identified by drug regulatory agencies.

Design

We conducted a systematic review and meta-analysis of randomised controlled trials (RCT). Six large databases were searched from inception to May 2018. Random effects models were used to estimate pooled relative risks (RRs).

Intervention

SGLT2 inhibitors, compared with placebo or active comparators.

Primary outcomes

Acute kidney injury (AKI), diabetic ketoacidosis (DKA), urinary tract infections (UTI), bone fractures and lower limb amputations.

Results

We screened 2418 citations of which 109 were included. Most studies included one of four SGLT2 inhibitors, dapagliflozin, canagliflozin, empagliflozin and ipragliflozin. When compared with placebo, SGLT2 inhibitors were found to be significantly protective against AKI (RR=0.59; 95% CI 0.39 to 0.89; I2=0.0%), while no difference was found for DKA (RR 0.66; 95% CI 0.30 to 1.45, I2=0.0%), UTI (RR 1.02; 95% CI 0.95 to 1.09, I2=0.0%) or bone fracture (RR 0.87; 95% CI 0.69 to 1.09, I2=1.3%). Three studies reported on amputation, with one finding a significant increase risk. No increased risk for either outcome was found when compared with active controls. Subgroup analysis did show an increased risk of UTI with dapagliflozin only (RR 1.21; 95% CI 1.02 to 1.43, I2=0.0%), but no other analysis supported an increased risk of AKI, DKA, UTI or fracture.

Conclusions

Current evidence from RCTs does not suggest an increased risk of harm with SGLT2 inhibitors as a class over placebo or active comparators with respect to AKI, DKA, UTI or fracture. However, wide CIs for many comparisons suggest limited precision, and therefore clinically important adverse events cannot be ruled out. Dapagliflozin, appears to independently increase the risk of UTI, although the mechanism for this intraclass variation in risk is unclear.

PROSPERO registration number

CRD42016038715.



http://bit.ly/2S0AuyB

Can propensity score matching be applied to cross-sectional data to evaluate Community-Based Rehabilitation? Results of a survey implementing the WHOs Community-Based Rehabilitation indicators in Vietnam

Objectives

Community-Based Rehabilitation (CBR) is a multi-sectoral approach working to equalise opportunities and include people with disabilities in all aspects of life. The complexity of CBR and often limited resources lead to challenges when attempting to quantify its effectiveness, with randomisation and longitudinal data rarely possible. Statistical methods, such as propensity score matching (PSM), offer an alternative approach to evaluate a treatment when randomisation is not feasible. The aim of this study is to examine whether PSM can be an effective method to facilitate evaluations of results in CBR when data are cross-sectional.

Design

Cross-sectional survey.

Setting and participants

Data were collected using the WHO's CBR Indicators in Vietnam, with treatment assignment (participating in CBR or not) determined by province of residence. 298 participants were selected through government records.

Results

PSM was conducted using one-to-one nearest neighbour method on 10 covariates. In the unmatched sample, significant differences between groups were found for six of the 10 covariates. PSM successfully adjusted for bias in all covariates in the matched sample (74 matched pairs). A paired t-test compared the outcome of 'community inclusion' (a score based on selected indicators) between CBR and non-CBR participants for both the matched and unmatched samples, with CBR participants found to have significantly worse community inclusion scores (mean=17.86, SD=6.30, 95% CI 16.45 to 19.32) than non-CBR participants (mean=20.93, SD=6.16, 95% CI 19.50 to 22.35); t(73)=3.068, p=0.001. This result did not differ between the matched and unmatched samples.

Conclusion

PSM successfully reduced bias between groups, though its application did not affect the tested outcome. PSM should be considered when analysing cross-sectional CBR data, especially for international comparisons where differences between populations may be greater.



http://bit.ly/2S2OVSx

Evaluation of the intensive outpatient clinic: study protocol for a prospective study of high-cost, high-need patients in the University of Utah Health system

Introduction

The University of Utah (UofU) Health intensive outpatient clinic (IOC) is a primary care clinic for medically complex (high-cost, high-need) patients with Medicaid. The clinic consists of a multidisciplinary care team aimed at providing coordinated, comprehensive and patient-centred care. The protocol outlines the quantitative design of an evaluation study to determine the IOC's effects on reducing healthcare utilisation and costs, as well as improving patient-reported health outcomes and quality of care.

Methods and analysis

High-risk patients, with high utilisation and multiple chronic illnesses, were identified in the Medicaid ACO population managed by the UofU Health plans for IOC eligibility. A prospective, case-control study design is being used to match 100 IOC patients to 200 control patients (receiving usual care within the UofU) based on demographics, health utilisation and medical complexity for evaluating the primary outcome of change in healthcare utilisation and costs. For the secondary outcomes of patient health and care quality, a prepost design will be used to examine within-person change across the 18 months of follow-up (ie, before and after IOC intervention). Logistic regression and hierarchical, longitudinal growth modelling are the two primary modelling approaches.

Ethics and dissemination

This work has received ethics approval by the UofU Institutional Review Board. Results from the evaluation of primary and secondary outcomes will be disseminated in scientific research journals and presented at national conferences.



http://bit.ly/2UzYe9w

Temporal trends in neonatal mortality and morbidity following spontaneous and clinician-initiated preterm birth in Washington State, USA: a population-based study

Objective

After a decade of increase, the preterm birth (PTB) rate has declined in the USA since 2006, with the largest decline at late preterm (34–36 weeks). We described concomitant changes in gestational age-specific rates of neonatal mortality and morbidity following spontaneous and clinician-initiated PTB among singleton infants.

Design, setting and participants

This retrospective population-based study included 754 763 singleton births in Washington State, USA, 2004–2013, using data from birth certificates and hospitalisation records. PTB subtypes included preterm premature rupture of membranes (PPROM), spontaneous onset of labour and clinician-initiated delivery.

Outcome measures

The primary outcomes were neonatal mortality and a composite outcome including death or severe neonatal morbidity. Temporal trends in the outcomes and individual morbidities were assessed by PTB subtype. Logistic regression yielded adjusted odds ratios (AOR) per 1 year change in outcome and 95% CI.

Results

The rate of PTB following PPROM and spontaneous labour declined, while clinician-initiated PTB increased (all p<0.01). Overall neonatal mortality remained unchanged (1.3%; AOR 0.99, CI 0.95 to 1.02), though gestational age-specific mortality following clinician-initiated PTB declined at 32–33 weeks (AOR 0.85, CI 0.74 to 0.97) and increased at 34–36 weeks (AOR 1.10, CI 1.01 to 1.20). The overall rate of the composite outcome increased (from 7.9% to 11.9%; AOR 1.06, CI 1.05 to 1.08). Among late preterm infants, combined mortality or severe morbidity increased following PPROM (AOR 1.13, CI 1.08 to 1.18), spontaneous labour (AOR 1.09, CI 1.06 to 1.13) and clinician-initiated delivery (AOR 1.10, CI 1.07 to 1.13). Neonatal sepsis rates increased among all preterm infants (AOR 1.09, CI 1.08 to 1.11).

Conclusions

Timing of obstetric interventions is associated with infant health outcomes at preterm. The temporal decline in late PTB among singleton infants was associated with increased mortality among late preterm infants born following clinician-initiated delivery and increased combined mortality or severe morbidity among all late preterm infants, mainly due to increased rate of sepsis.



http://bit.ly/2S1XKfw

Qualitative study to elicit patients and primary care physicians perspectives on the use of a self-management mobile health application for knee osteoarthritis

Objective

To elicit perspectives of family physicians and patients with knee osteoarthritis (KOA) on KOA, its treatment/management and the use of a mobile health application (app) to help patients self-manage their KOA.

Design

A qualitative study using Cognitive Task Analysis for physician interviews and peer-to-peer semistructured interviews for patients according to the Patient and Community Engagement Research (PaCER) method.

Setting

Primary care practices and patient researchers at an academic centre in Southern Alberta.

Participants

Intentional sampling of family physicians (n=4; 75% women) and patients with KOA who had taken part in previous PaCER studies and had experienced knee pain on most days of the month at any time in the past (n=5; 60% women).

Results

Physician and patient views about KOA were starkly contrasting. Patient participants expressed that KOA seriously impacted their lives and lifestyles, and they wanted their knee pain to be considered as important as other health problems. In contrast, physicians uniformly conceptualised KOA as a relatively minor health problem, although they still recognised it as a painful condition that often limits patients' activities. Consequently, physicians did not regard KOA as a condition to be proactively and aggressively managed. The gap between physicians' and patients' conceptualisation of KOA and its treatment extended to the use of an app for self-management. While patients were supportive of the app, physicians were sceptical of its use and focused more on accountability and patient resources.

Conclusions

The clear discord between physicians' mental models and patients' lived experience and perceived needs around KOA emphasised a gap in understanding and communication about treatment and management of KOA. As such, this preliminary and formative research will inform a codesign approach to develop an app that will act as a communications tool between patients and physicians, enabling patient–physician discussions regarding modifiable self-management options based on a patient's perspectives and needs.



http://bit.ly/2UycRtS

Health Outcomes, Pathogenesis and Epidemiology of Severe Acute Malnutrition (HOPE-SAM): rationale and methods of a longitudinal observational study

Introduction

Mortality among children hospitalised for complicated severe acute malnutrition (SAM) remains high despite the implementation of WHO guidelines, particularly in settings of high HIV prevalence. Children continue to be at high risk of morbidity, mortality and relapse after discharge from hospital although long-term outcomes are not well documented. Better understanding the pathogenesis of SAM and the factors associated with poor outcomes may inform new therapeutic interventions.

Methods and analysis

The Health Outcomes, Pathogenesis and Epidemiology of Severe Acute Malnutrition (HOPE-SAM) study is a longitudinal observational cohort that aims to evaluate the short-term and long-term clinical outcomes of HIV-positive and HIV-negative children with complicated SAM, and to identify the risk factors at admission and discharge from hospital that independently predict poor outcomes. Children aged 0–59 months hospitalised for SAM are being enrolled at three tertiary hospitals in Harare, Zimbabwe and Lusaka, Zambia. Longitudinal mortality, morbidity and nutritional data are being collected at admission, discharge and for 48 weeks post discharge. Nested laboratory substudies are exploring the role of enteropathy, gut microbiota, metabolomics and cellular immune function in the pathogenesis of SAM using stool, urine and blood collected from participants and from well-nourished controls.

Ethics and dissemination

The study is approved by the local and international institutional review boards in the participating countries (the Joint Research Ethics Committee of the University of Zimbabwe, Medical Research Council of Zimbabwe and University of Zambia Biomedical Research Ethics Committee) and the study sponsor (Queen Mary University of London). Caregivers provide written informed consent for each participant. Findings will be disseminated through peer-reviewed journals, conference presentations and to caregivers at face-to-face meetings.



http://bit.ly/2S4OQ0H

'I did not check if the teacher gave feedback: a qualitative analysis of Taiwanese postgraduate year 1 trainees talk around e-portfolio feedback-seeking behaviours

Objectives

Despite feedback being an extensively researched and essential component of teaching and learning, there is a paucity of research examining feedback within a medical education e-portfolio setting including feedback-seeking behaviours (FSBs). FSBs can be understood within a cost–value perspective. The objective of this research is to explore the factors that influence postgraduate year 1 (PGY1) trainee doctors' FSBs via e-portfolios.

Setting

Postgraduate education provision in the largest teaching hospital in Taiwan.

Participants

Seventy-one PGY1s (66% male).

Methods

A qualitative semistructured one-to-one interview method was adopted. Interviews were audio recorded, transcribed verbatim, anonymised and checked for completeness. Data were analysed inductively via thematic framework analysis and deductively informed using FSB theory. The process comprised data familiarisation, identification of the themes, charting and data interpretation.

Results

Two main themes of FSB related and e-portfolio related were identified. We present the theme focussing on FSB here to which n=32 (22 males, 10 females) of the n=71 participants contributed meaningfully. Subthemes include factors variously affecting PGY1s' positive and negative FSBs via e-portfolios at the individual, process and technological levels. These factors include learner-related (internal values vs social influence, forced reflection); teacher-related (committed educators vs superficial feedback); technology-related (face-saving vs lagging systems; inadequate user-interface) and process-related (delayed feedback, too frequent feedback) factors.

Conclusions

Our findings reveal the complexity of PGY1s' FSBs in an e-portfolio context and the interaction of numerous facilitating and inhibiting factors. Further research is required to understand the range of facilitating and inhibiting factors involved in healthcare learners' FSBs across different learning, social, institutional and national cultural settings.



http://bit.ly/2UycOOI

Systematic scoping review protocol for clinical prediction rules (CPRs) in the management of patients with spinal cord injuries

Introduction

The upsurge in the use of clinical prediction models in general medical practice is a result of evidence-based practice. However, the total number of clinical prediction rules (CPRs) currently being used or undergoing impact analysis in the management of patients who have sustained spinal cord injuries (SCIs) is unknown. This scoping review protocol will describe the current CPRs being used and highlight their possible strengths and weaknesses in SCI management.

Methods and analysis

Arksey and O'Malley's scoping review framework will be used. The following databases will be searched to identify relevant literature relating to the use of CPRs in the management of patients who have sustained an SCI: PubMed, Cumulative Index of Nursing and Allied Health Literature (CINAHL), ScienceDirect, EBSCOhost, Medline, OvidMedline and Google Scholar. Grey literature as well as reference lists of included studies will be searched. All studies relating to the use of CPRs in the management of patients with SCIs will be included. Literature searches and data extraction will be performed independently by two groups of reviewers.

Ethics and dissemination

Ethical clearance is not required for this scoping review study since only secondary data sources will be used. The findings of this review will be disseminated by means of peer-reviewed publication and conference proceedings. The final paper will be submitted for publication. Results of this review will also be presented at relevant conferences and disseminated to important stakeholders such as practicing physicians within specialised spinal care facilities within South Africa.



http://bit.ly/2S95j4k

Impact of point-of-care C reactive protein in ambulatory care: a systematic review and meta-analysis

Objective

The aim of this review was to collate all available evidence on the impact of point-of-care C reactive protein (CRP) testing on patient-relevant outcomes in children and adults in ambulatory care.

Design

This was a systematic review to identify controlled studies assessing the impact of point-of-care CRP in patients presenting to ambulatory care services. Ovid Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane CENTRAL, DARE, Science Citation Index were searched from inception to March 2017.

Eligibility criteria for selecting studies

Controlled studies assessing the impact of point-of-care CRP in patients presenting to ambulatory care services, measuring a change in clinical care, including but not limited to antibiotic prescribing rate, reconsultation, clinical recovery, patient satisfaction, referral and additional tests. No language restrictions were applied.

Data extraction

Data were extracted on setting, date of study, a description of the intervention and control group, patient characteristics and results. Methodological quality of selected studies and assessment of potential bias was assessed independently by two authors using the Cochrane Risk of Bias tool.

Results

11 randomised controlled trials and 8 non-randomised controlled studies met the inclusion criteria, reporting on 16 064 patients. All included studies had a high risk of performance and selection bias. Compared with usual care, point-of-care CRP reduces immediate antibiotic prescribing (pooled risk ratio 0.81; 95% CI 0.71 to 0.92), however, at considerable heterogeneity (I2=72%). This effect increased when guidance on antibiotic prescribing relative to the CRP level was provided (risk ratios of 0.68; 95% CI 0.63 to 0.74 in adults and 0.56; 95% CI 0.33 to 0.95 in children). We found no significant effect of point-of-care CRP testing on patient satisfaction, clinical recovery, reconsultation, further testing and hospital admission.

Conclusions

Performing a point-of-care CRP test in ambulatory care accompanied by clinical guidance on interpretation reduces the immediate antibiotic prescribing in both adults and children. As yet, available evidence does not suggest an effect on other patient outcomes or healthcare processes.

PROSPERO registration number

CRD42016035426; Results.



http://bit.ly/2UE9d1T

Four‐dimensional functional cortical maps of visual and auditory language: Intracranial recording

Summary

Objective

The strength of presurgical language mapping using electrocorticography (ECoG) is its outstanding signal fidelity and temporal resolution, but the weakness includes limited spatial sampling at an individual patient level. By averaging naming‐related high‐gamma activity at nonepileptic regions across a large number of patients, we provided the functional cortical atlases animating the neural dynamics supporting visual‐object and auditory‐description naming at the whole brain level.

Methods

We studied 79 patients who underwent extraoperative ECoG recording as epilepsy presurgical evaluation, and generated time‐frequency plots and animation videos delineating the dynamics of naming‐related high‐gamma activity at 70‐110 Hz.

Results

Naming task performance elicited high‐gamma augmentation in domain‐specific lower‐order sensory areas and inferior‐precentral gyri immediately after stimulus onset. High‐gamma augmentation subsequently involved widespread neocortical networks with left hemisphere dominance. Left posterior temporal high‐gamma augmentation at several hundred milliseconds before response onset exhibited a double dissociation; picture naming elicited high‐gamma augmentation preferentially in regions medial to the inferior‐temporal gyrus, whereas auditory naming elicited high‐gamma augmentation more laterally. The left lateral prefrontal regions including Broca's area initially exhibited high‐gamma suppression subsequently followed by high‐gamma augmentation at several hundred milliseconds before response onset during both naming tasks. Early high‐gamma suppression within Broca's area was more intense during picture compared to auditory naming. Subsequent lateral‐prefrontal high‐gamma augmentation was more intense during auditory compared to picture naming.

Significance

This study revealed contrasting characteristics in the spatiotemporal dynamics of naming‐related neural modulations between tasks. The dynamic atlases of visual and auditory language might be useful for planning of epilepsy surgery. Differential neural activation well explains some of the previously reported observations of domain‐specific language impairments following resective epilepsy surgery. Video materials might be beneficial for the education of lay people about how the brain functions differentially during visual and auditory naming.



http://bit.ly/2CZvdwO

Central Carbon Metabolism Regulates Macrophage Antitumor Activity [Research Watch]

CpG rewires macrophage metabolism to bypass inhibitory CD47 signals and enhance antitumor activity.



http://bit.ly/2MIeiTQ

ctDNA Profiling of Cerebrospinal Fluid Characterizes Glioma Evolution [Research Watch]

ctDNA analysis of CSF recapitulates the genomic evolution of brain tumors.



http://bit.ly/2DQmezQ

Autophagy Prevents Bypass of Replicative Crisis [Research Watch]

Autophagic cell death during replicative crisis prevents further accumulation of genomic instability.



http://bit.ly/2MMBzEq

AIs Recommended for Breast Cancer Prevention [News in Brief]

Draft guidelines from the USPSTF suggest that women at high risk for the disease consider using the drugs.



http://bit.ly/2DPDRzO

How to Successfully Navigating a Telephone and Video Interview



http://bit.ly/2MLV4N9

Amazon forest-to-agriculture conversion alters rhizosphere microbiome composition while functions are kept

Abstract
The conversion of native forest to agriculture is the main cause of microbial biodiversity loss in Amazon soils. In order to better understand this effect, we used metagenomics to investigate microbial patterns and functions in bulk soil and rhizosphere of soybean, in a long-term forest-to-agriculture conversion. Long-term forest-to-agriculture led to microbial homogenization and loss of diversity in both bulk soil and rhizosphere, mainly driven by decreasing aluminum concentration and increased cations saturation in soil, due liming and fertilization in long-term no-till cropping. Data revealed that long-term no-till culminated with decrease in Acidobacteria, Actinobacteria and Proteobacteria abundances. However, α- and β-Proteobacteria abundances were higher in rhizosphere than in bulk soil, regardless time after forest-to-agriculture conversion. Changes in functional potential occurred predominantly in bulk soil, with decreases in functions related to potassium metabolism and virulence, disease and defense while functions related to nucleic acids metabolism increased. Functions in soybean rhizosphere remained stable, except for those related to potassium metabolism, which decreased after 20-year no-till cropping. Together, our results show that soybean root system selects microbial taxa via trade-offs, to keep functional resilience in the rhizosphere microbiome along time.

http://bit.ly/2t0RG84

Suppression of arbuscular mycorrhizal fungal activity in a diverse collection of non-cultivated soils

Abstract
Most plants form symbiotic associations with arbuscular mycorrhizal fungi (AMF). AMF increase the uptake of plant nutrients by extending their extra-radical mycelium (ERM) in the soil where other groups of microorganisms may suppress the activity of the ERM. However, little is known about such suppression in natural soils. This work aimed to investigate the incidence of AMF suppression among soils sampled from highly variable natural ecosystems, and used 33P uptake by the ERM to evaluate AMF activity. A second aim was to identify factors behind the observed AMF-suppression. We found that AMF-suppressiveness varied markedly among natural soils and occurred more frequently in low pH than in high pH soils. A previous study for cultivated soils revealed a strong biological component of suppressiveness against AMF, and in accordance we found that the composition of both fungal and bacterial communities differed significantly between AMF-suppressive and non-suppressive natural soils. Acidobacteria, Acidothermus, Xanthomonadaceae, Archaeorhizomyces sp., Mortierella humilis and some Mycena spp. were significantly more abundant in AMF-suppressive soils and may therefore be direct antagonists of AMF. This implies that the functioning of AMF in natural ecosystems is strongly modulated by specific soil microbes.

http://bit.ly/2HNutRb

Aortic Arch Thrombosis Associated with Fetal Cytomegalovirus Viremia

AJP Rep 2019; 09: e23-e26
DOI: 10.1055/s-0038-1675631

Cytomegalovirus(CMV) associated thrombosis has been reported sporadically in the medical literature; however, its antenatal scenario has not been documented. We herein present the antenatal, Doppler's ultrasound and magnetic resonance angiographic features of thrombosis in the aortic arch showing extension toward the medial lumen of the brachiocephalic trunk with critical occlusion of the left common carotid artery and left subclavian artery in a term fetus to raise obstetricians'/ neonatologists'/pediatric cardiologists' awareness for the association between CMV viremia and intrauterine thrombosis that caused cerebral injury, neurodevelopmental impairment, and permanent sequela.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text



http://bit.ly/2G5LDb1

Direct-to-Doctor Payments May Increase Opioid Prescribing

FRIDAY, Feb. 1, 2019 -- Physicians who receive direct pharmaceutical payments for opioid prescribing prescribe more opioids, especially hydrocodone and oxycodone, according to a study published online Jan. 22 in Addiction. Thuy D. Nguyen, Ph.D.,...

http://bit.ly/2Bg5vnP

Shortage of Anxiety Drug Creates Alarm Among Patients, Doctors

FRIDAY, Feb. 1, 2019 -- A shortage of the anti-anxiety drug buspirone in the United States has patients and doctors concerned. Buspirone is among one of the generic drugs for which prices have fallen so low that many manufacturers claim they cannot...

http://bit.ly/2TsREBx

Discontinuing TNFi Before Gestational Week 20 Is Feasible

FRIDAY, Feb. 1, 2019 -- Discontinuing tumor necrosis factor inhibitors (TNFi) before gestational week 20 in women with well-controlled rheumatoid arthritis (RA) or juvenile idiopathic arthritis (JIA) is not associated with disease worsening in late...

http://bit.ly/2TtcLUb

Physician Burnout Tied to Ability to Address Social Needs

FRIDAY, Feb. 1, 2019 -- Improving clinic capacity to respond to patients' social needs may reduce primary care physician burnout, according to a study published in the January-February issue of the Journal of the American Board of Family...

http://bit.ly/2BeHwp8

Nuclear Theranostics in Taiwan

Abstract

Boron neutron capture therapy and Y-90 radioembolization are emerging therapeutic methods for uncontrolled brain cancers and hepatic cancers, respectively. These advanced radiation therapies are heavily relied on theranostic nuclear medicine imaging before the therapy for the eligibility of patients and the prescribed-dose simulation, as well as the post-therapy scanning for assessing the treatment efficacy. In Taiwan, the Taipei Veterans General Hospital is the only institute performing the BNCT and also the leading institute performing Y-90 radioembolization. In this article, we present our single institute experiences and associated theranostic nuclear medicine approaches for these therapies.



http://bit.ly/2UCUZ1d

Effect of Treatment on the Risk of Viral Infections in Inflammatory Bowel Disease



http://bit.ly/2G6bsHI

Association Between Renal Function Pattern and Mortality in Patients with Cirrhosis

Renal dysfunction increases risk of death for patients with cirrhosis. We investigated whether mortality differs significantly among patients with acute kidney injury (AKI), chronic kidney disease (CKD), and both.

http://bit.ly/2UvP9OY

Validation of a Model for Identification of Patients With Compensated Cirrhosis at High Risk of Decompensation

It is important to rapidly identify patients with advanced liver disease. Routine tests to assess liver function and fibrosis provide data that can be used to determine patients' prognoses. We tested the validated the ability of combined data from the ALBI and FIB-4 scoring systems to identify patients with compensated cirrhosis at highest risk for decompensation.

http://bit.ly/2G66knf

No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma—a Mendelian Randomization Study

Epidemiology studies of circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risk of esophageal adenocarcinoma (EAC) have produced conflicting results. We conducted a Mendelian randomization study to determine the associations between circulating concentrations of 25(OH)D and risks of EAC and its precursor, Barrett's esophagus (BE).

http://bit.ly/2UFsMXF

Toll-Like Receptor 4 and Matrix Metalloproteases 11 and 13 as Predictors of Tumor Recurrence and Survival in Stage II Colorectal Cancer

Abstract

Current clinical-pathologic stratification factors do not allow clear identification of high-risk stage II colorectal cancer (CRC) patients. Therefore, the identification of additional prognostic markers is desirable. Toll-like receptor (TLR)-4 is activated during tumorigenesis and matrix metalloproteases (MMPs) are involved in invasion and metastasis. We aimed to evaluate the expression and clinical relevance of TLR4, MMP11 and MMP13 for patients with stage II CRC. Immunohistochemistry was used to study the expression of TLR4, MMP11 and MMP13 in 96 patients with stage II CRC. We measured the global expression and the expression by different cell types (tumor cells, cancer-associated fibroblasts (CAFs) and mononuclear inflammatory cells (MICs)). The potential relationship between expressions of factors and different prognostic variables were evaluated. Our results show significant relationships between either TLR4 expression by tumor cells and MMP11 expression by CAFs and high risk of tumor recurrence. In addition, the concurrence of age ≥ 75 years and the non-expression of MMP11 by CAFs identify a subgroup of patients with a good prognosis. Our results show that TLR4 expression by tumor cells and MMP11 expression by CAFs may to improve the identification of patients with stage II CRC with a high-risk of relapse.



http://bit.ly/2RvfLOc

Removal of intraductal migrated biliary fully covered self-expandable metal stents: the “SEMS in SEMS” technique



http://bit.ly/2sWNCpw

The pocket-creation method facilitates colonic endoscopic submucosal dissection (with video)

Colonic endoscopic submucosal dissection (ESD) is more difficult than rectal ESD because of poor maneuverability of the endoscope due to physiological flexion, peristalsis and respiratory movements. The aim of this study is to assess the usefulness of the pocket-creation method (PCM) for colonic ESD compared with the conventional method (CM) regardless of lesion shape or location.

http://bit.ly/2HIpeSv

Local-therapy decisional regret in older women with breast cancer: A population-based study

Older (≥67 years) breast cancer survivors diagnosed in 2009 and treated with 1 of 5 local-therapy options [lumpectomy plus whole breast irradiation, brachytherapy, or endocrine therapy (Lump+WBI, Lump+Brachy, or Lump-alone) or mastectomy -/+ radiation (Mast-alone or Mast+RT)] were surveyed to examine their local-therapy treatment-related decisional regret 6-years after diagnosis. Local-therapy regret afflicted nearly one-quarter of our cohort and was associated with black race, less education, and more extensive nodal dissection but not breast surgery.

http://bit.ly/2Tq0jET

Voxel-based analysis for identification of urethro-vesical subregions predicting urinary toxicity after prostate cancer radiotherapy

Risk estimation of genitourinary (GU) toxicity after prostate radiotherapy is generally based on bladder dose-volume histograms (DVHs), disregarding any spatial dose-distribution information. We used a voxel-based approach to explore dosimetric regional differences in the bladder and the urethra associated with GU toxicity. The dose delivered to specific subregions of the urethra and the bladder was predictive of specific urinary symptoms, whereas the dose delivered to the whole bladder was less or not predictive.

http://bit.ly/2Be9RvJ

Impact of radiation target volume on health-related quality of life in patients with low grade glioma in the two-year period post treatment – XXX

It is currently unknown whether increasing radiotherapy volume has a negative impact on the health-related quality of life (HRQoL) of low-grade glioma (LGG) patients in the short-term. The aim was to examine if the size of the target volume is independently associated with HRQoL.

http://bit.ly/2Tq0hgf

HEART Score Risk Stratification of Low-Risk Chest Pain Patients in the Emergency Department: A Systematic Review and Meta-Analysis

The objectives of this systematic review and meta-analysis are to appraise the evidence in regard to the diagnostic accuracy of a low-risk History, ECG, Age, Risk Factors, and Troponin (HEART) score for prediction of major adverse cardiac events in emergency department (ED) patients. These included 4 subgroup analyses: by geographic region, the use of a modified low-risk HEART score (traditional HEART score [0 to 3] in addition to negative troponin results), using conventional versus high-sensitivity troponin assays in the HEART score, and a comparison of different post–ED-discharge patient follow-up intervals.

http://bit.ly/2BhKSaH

Reproductive Health Issues for Young Women with Breast Cancer: Emerging Strategies for Difficult Situations



http://bit.ly/2HNVJij

Chronic Implantation of Whole-cortical Electrocorticographic Array in the Common Marmoset

We have developed a whole-cortical electrocorticographic array for the common marmoset that continuously covers almost the entire lateral surface of cortex, from the occipital pole to the temporal and frontal poles. This protocol describes a chronic implantation procedure of the array in the epidural space of the marmoset brain.

http://bit.ly/2S1WEjT

Impact of Collateral Filling Delay on the Development of Subacute Complications After Acute Ischemic Stroke

Abstract

Purpose

Leptomeningeal collaterals play a pivotal role in acute ischemic stroke. While most collateral scores rely on subjective visual analysis, an objective quantification is possible using dynamic computed tomography (CT) angiography (dynCTA). The aim was to determine the value of collateral filling delay (CFD) as assessed by dynCTA for predicting subacute stroke complications.

Methods

All subjects with isolated prebifurcation middle cerebral artery M1 occlusions were selected from an initial cohort of 2635 patients who underwent multiparametric CT for suspected stroke. The CFD was defined as the difference in time to peak enhancement between M2 segments of both hemispheres. Logistic regression analysis of CFD for space-occupying infarction (≥5 mm shift of brain tissue over the midline), parenchymal hematoma, and hemorrhagic transformation on follow-up imaging was performed.

Results

In this study 78 patients (47 female, median age 74 years) were included. The median CFD was 6.31 s (interquartile range [IQR] 4.00–8.64). The CFD values were correlated with qualitative collateral scores (p < 0.05). Higher CFD was associated with the development of space-occupying infarction in univariable (odds ratio, OR = 1.28; p = 0.002) and multivariable regression analysis (OR = 1.48; p = 0.004). The CFD had no association with parenchymal hematoma or hemorrhagic transformation (p > 0.05).

Conclusion

A high CFD may serve as reproducible measure for collateralization and indicate development of increased risk of space-occupying infarction.



http://bit.ly/2t2cQTu

Computational design of structured loops for new protein functions

Authors: Kundert, Kale / Kortemme, Tanja


http://bit.ly/2FVVKhA

Frontmatter



http://bit.ly/2sv9Qid

Assay of β-glucosidase 2 (GBA2) activity using lithocholic acid β-3-O-glucoside substrate for cultured fibroblasts and glucosylceramide for brain tissue

Authors: Harzer, Klaus / Yildiz, Yildiz / Beck-Wödl, Stefanie


http://bit.ly/2MexCrD

Mitochondria, Apoptosis and Cancer (MAC) 2017

Authors: Turk, Boris


http://bit.ly/2MexwQN

Highly flexible, IgG-shaped, trivalent antibodies effectively target tumor cells and induce T cell-mediated killing

Authors: Dickopf, Steffen / Lauer, Matthias E. / Ringler, Philippe / Spick, Christian / Kern, Peter / Brinkmann, Ulrich


http://bit.ly/2SKxx1g

ASO Author Reflections: Tumor-Infiltrating NETs are New Biomarkers to Predict Postsurgical Survival for Patients with Pancreatic Ductal Adenocarcinoma



http://bit.ly/2Rx2Uer

Chemotherapeutic paclitaxel and cisplatin differentially induce pyroptosis in A549 lung cancer cells via caspase-3/GSDME activation

Abstract

Gasdermin E (GSDME) has an important role in inducing secondary necrosis/pyroptosis. Upon apoptotic stimulation, it can be cleaved by activated caspase-3 to generate its N-terminal fragment (GSDME-NT), which executes pyroptosis by perforating the plasma membrane. GSDME is expressed in many human lung cancers including A549 cells. Paclitaxel and cisplatin are two representative chemotherapeutic agents for lung cancers, which induce apoptosis via different action mechanisms. However, it remains unclear whether they can induce GSDME-mediated secondary necrosis/pyroptosis in lung A549 cancer cells. Here we showed that both paclitaxel and cisplatin evidently induced apoptosis in A549 cells as revealed by the activation of multiple apoptotic markers. Notably, some of the dying cells displayed characteristic morphology of secondary necrosis/pyroptosis, by blowing large bubbles from the cellular membrane accompanied by caspase-3 activation and GSDME-NT generation. But the ability of cisplatin to induce this phenomenon was much stronger than that of paclitaxel. Consistent with this, cisplatin triggered much higher activation of caspase-3 and generation of GSDME-NT than paclitaxel, suggesting that the levels of secondary necrosis/pyroptosis correlated with the levels of active caspase-3 and GSDME-NT. Supporting this, caspase-3 specific inhibitor (Ac-DEVD-CHO) suppressed cisplatin-induced GSDME-NT generation and concurrently reduced the secondary necrosis/pyroptosis. Besides, GSDME knockdown significantly inhibited cisplatin- but not paclitaxel-induced secondary necrosis/pyroptosis. These results indicated that cisplatin induced higher levels of secondary necrosis/pyroptosis in A549 cells than paclitaxel, suggesting that cisplatin may provide additional advantages in the treatment of lung cancers with high levels of GSDME expression.



http://bit.ly/2D6LCPY

An Iodide-Yellow Fluorescent Protein-Gap Junction-Intercellular Communication Assay

Here, we present a protocol for a novel gap junction intercellular communication assay designed for the high-throughput screening of gap junction-modulating chemicals for drug discovery and toxicological assessment.

http://bit.ly/2BpyQfJ

Methodological issues are important in cannabinoids determination in bronchoalveolar lavage

Authors: Poletti, Venerino / Ravaglia, Claudia


http://bit.ly/2HG1fn0

Therapeutic drug monitoring (TDM) of 5-fluorouracil (5-FU): new preanalytic aspects

Authors: Mindt, Sonani / Aida, Sihem / Merx, Kirsten / Müller, Annette / Gutting, Tobias / Hedtke, Maren / Neumaier, Michael / Hofheinz, Ralf-Dieter


http://bit.ly/2SlzIf3

Determination of sigma score based on biological variation for haemostasis assays: fit-for-purpose for daily practice?

Authors: Hollestelle, Martine J. / Ruinemans-Koerts, Janneke / Idema, René N. / Meijer, Piet / de Maat, Moniek P.M.


http://bit.ly/2RKJKpq

Sample matrix and high-sensitivity cardiac troponin I assays

Authors: Kavsak, Peter A. / Roy, Chantele / Malinowski, Paul / Clark, Lorna / Lamers, Shana / Bamford, Karen / Hill, Stephen / Worster, Andrew / Jaffe, Allan S.


http://bit.ly/2RkU3kT

Determination of haemoglobin derivatives in aged dried blood spot to estimate haematocrit

Authors: Zakaria, Rosita / Allen, Katrina J. / Koplin, Jennifer J. / Crinis, Nick / De Rosa, Lidia / Roche, Peter / Greaves, Ronda F.


http://bit.ly/2H6spDv

Harmonizing by reducing inter-run variability: performance evaluation of a quality assurance program for antinuclear antibody detection by indirect immunofluorescence

Authors: Bogaert, Laura / Van den Bremt, Stefanie / Schouwers, Sofie / Bossuyt, Xavier / Van Hoovels, Lieve


http://bit.ly/2TwrrBw

Faecal calprotectin in inflammatory bowel diseases: a review focused on meta-analyses and routine usage limitations

Authors: Laserna-Mendieta, Emilio J. / Lucendo, Alfredo J.


http://bit.ly/2CTnstG

Does Gender Nonconforming Behavior in Early Childhood Predict Adolescents’ Depressive Symptoms?

Abstract

Gender nonconforming behavior (GNB) is a risk factor for poorer psychological adjustment, but little is known about whether preschool-age children displaying GNB are at risk for depressive symptoms during adolescence. We examined maternal report of GNB at age 4–5 years-old as a predictor of adolescents' depressive symptoms at age 16–17 years-old in a longitudinal study of U.S. children from a predominantly low SES (61% received Aid to Families with Dependent Children) and African American (90%) sample. Youth with GNB in early childhood (n = 10) reported more depressive symptoms during adolescence than did their peers without GNB (n = 115), and this relationship remained after controlling for covariates (environmental risk, prenatal exposure, and neonatal medical problems). Our findings suggest that early GNB may be a risk factor for the development of depressive symptoms in adolescence. Further research is needed to replicate the current findings with a larger sample and to identify the underlying mechanisms by which GNB may increase risk for depressive symptoms. If replicated, the findings further highlight the need for both professionals and parents to become aware of the potential challenges that children with GNB face and to become knowledgeable about ways to facilitate healthy adjustment among gender nonconforming youth.



http://bit.ly/2MP06ss

Maternal Factors Predict Postpartum Depression Trajectory

FRIDAY, Feb. 1, 2019 -- Four maternal characteristics can predict 12-month trajectories for women with postpartum depression with 72.8 percent accuracy, according to a study published online Jan. 15 in Depression & Anxiety. Sheehan D. Fisher,...

http://bit.ly/2Tto52M

Hearing Loss Linked to Subjective Cognitive Function Decline

FRIDAY, Feb. 1, 2019 -- For older men, hearing loss is associated with subjective cognitive function (SCF) decline, according to a study published online Jan. 29 in Alzheimer's & Dementia. Sharon G. Curhan, M.D., from Brigham and Women's...

http://bit.ly/2Be8flI

Mindfulness-Based Stress Reduction Also Benefits Chronic Pain

FRIDAY, Feb. 1, 2019 -- For patients with chronic pain (CP), both mindfulness-based stress reduction (MBSR) and cognitive behavioral therapy (CBT) improve physical functioning, pain intensity, and depression, according to a review published online...

http://bit.ly/2Tr4y34

Maternal Glucose in Pregnancy Tied to Child's Glucose Outcomes

FRIDAY, Feb. 1, 2019 -- In utero exposure to higher levels of maternal glucose is associated with higher glucose levels and insulin resistance during childhood, according to a study published online Jan. 7 in Diabetes Care. Denise M. Scholtens,...

http://bit.ly/2Tr4wZ0

CDC: Most Black HIV Patients Interviewed for Partner Services

FRIDAY, Feb. 1, 2019 -- More black index patients diagnosed with HIV are interviewed for partner services than all index patients combined, according to research published in the Feb. 1 issue of the U.S. Centers for Disease Control and Prevention...

http://bit.ly/2Be8ehE

Use of Image Analysis to ID HER2 Status in Breast Cancer Outlined

FRIDAY, Feb. 1, 2019 -- Recommendations have been developed to improve accuracy, precision, and reproducibility in the interpretation of human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) results for breast cancer with use of...

http://bit.ly/2Tto1QA

HPV Educational Video May Increase Vaccination Rates

FRIDAY, Feb. 1, 2019 -- Educational videos in pediatric clinics can increase rates of human papillomavirus (HPV) vaccination among adolescents, according to a study published in the January issue of Pediatrics. Brian E. Dixon, Ph.D., from Indiana...

http://bit.ly/2Be8cGy

Minimal Benefit for Decision Aid About Prolonged Ventilation

FRIDAY, Feb. 1, 2019 -- A personalized web-based decision aid about prolonged mechanical ventilation does not improve prognostic concordance between clinicians and surrogate decision makers, according to a study published online Jan. 29 in the...

http://bit.ly/2Be8bCu

January 2019 Briefing - Psychiatry

Here are what the editors at HealthDay consider to be the most important developments in Psychiatry for January 2019. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that are...

http://bit.ly/2TtnVII

January 2019 Briefing - Ophthalmology

Here are what the editors at HealthDay consider to be the most important developments in Ophthalmology for January 2019. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that...

http://bit.ly/2TpPG4P

January 2019 Briefing - Critical Care

Here are what the editors at HealthDay consider to be the most important developments in Critical Care for January 2019. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that...

http://bit.ly/2Be86Pc

January 2019 Briefing - Pathology

Here are what the editors at HealthDay consider to be the most important developments in Pathology for January 2019. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that are...

http://bit.ly/2TtnTk4

January 2019 Briefing - Allergy

Here are what the editors at HealthDay consider to be the most important developments in Allergy for January 2019. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that are the...

http://bit.ly/2TpCRYn

January 2019 Briefing - Otolaryngology

Here are what the editors at HealthDay consider to be the most important developments in Otolaryngology for January 2019. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that...

http://bit.ly/2BhFQLp



http://bit.ly/2S2l78U

Janus kinase 1/2 inhibition with baricitinib in the treatment of juvenile dermatomyositis

Sir,

http://bit.ly/2DQvlR7

Reply: Janus kinase 1/2 inhibition with baricitinib in the treatment of juvenile dermatomyositis

Sir,

http://bit.ly/2MIopbt

Spatial distribution of multiple sclerosis lesions in the cervical spinal cord

Abstract
Spinal cord lesions detected on MRI hold important diagnostic and prognostic value for multiple sclerosis. Previous attempts to correlate lesion burden with clinical status have had limited success, however, suggesting that lesion location may be a contributor. Our aim was to explore the spatial distribution of multiple sclerosis lesions in the cervical spinal cord, with respect to clinical status. We included 642 suspected or confirmed multiple sclerosis patients (31 clinically isolated syndrome, and 416 relapsing-remitting, 84 secondary progressive, and 73 primary progressive multiple sclerosis) from 13 clinical sites. Cervical spine lesions were manually delineated on T2- and T2*-weighted axial and sagittal MRI scans acquired at 3 or 7 T. With an automatic publicly-available analysis pipeline we produced voxelwise lesion frequency maps to identify predilection sites in various patient groups characterized by clinical subtype, Expanded Disability Status Scale score and disease duration. We also measured absolute and normalized lesion volumes in several regions of interest using an atlas-based approach, and evaluated differences within and between groups. The lateral funiculi were more frequently affected by lesions in progressive subtypes than in relapsing in voxelwise analysis (P < 0.001), which was further confirmed by absolute and normalized lesion volumes (P < 0.01). The central cord area was more often affected by lesions in primary progressive than relapse-remitting patients (P < 0.001). Between white and grey matter, the absolute lesion volume in the white matter was greater than in the grey matter in all phenotypes (P < 0.001); however when normalizing by each region, normalized lesion volumes were comparable between white and grey matter in primary progressive patients. Lesions appearing in the lateral funiculi and central cord area were significantly correlated with Expanded Disability Status Scale score (P < 0.001). High lesion frequencies were observed in patients with a more aggressive disease course, rather than long disease duration. Lesions located in the lateral funiculi and central cord area of the cervical spine may influence clinical status in multiple sclerosis. This work shows the added value of cervical spine lesions, and provides an avenue for evaluating the distribution of spinal cord lesions in various patient groups.

http://bit.ly/2DOuU9O

Occult gastrointestinal bleeding: two eyes are better than one

Introduction

A 55-year-old woman was referred for investigation of an incidental iron deficiency anaemia (haemoglobin 97 g/L; ferritin 10 ug/L and mean cell volume 71.3 fL). The patient had no gastrointestinal symptoms. Upper gastrointestinal endoscopy was normal, with no evidence of coeliac disease on duodenal biopsies. Colonoscopy showed diverticulosis.

A capsule endoscopy was then performed, using a new generation dual camera capsule (Mirocam MC2000, Intromedic, Seoul, Korea). This utilises a charge coupled device camera at each end of the capsule, with software that allows the images from each camera to be viewed individually or in combination. Each camera records at three frames per second, and each has a 170° field of view. Compared with a single camera capsule endoscope, dual camera devices generate twice the coverage area of the small bowel, with faster frame acquisition rates.1

Small bowel images from capsule camera 1 were entirely normal (figure 1). A small bowel...



http://bit.ly/2G5htEB

Cost-effectiveness of laparoscopic ileocaecal resection versus infliximab treatment of terminal ileitis in Crohns disease: the LIR!C Trial

Objective

Evaluate the cost-effectiveness of laparoscopic ileocaecal resection compared with infliximab in patients with ileocaecal Crohn's disease failing conventional therapy.

Design

A multicentre randomised controlled trial was performed in 29 centres in The Netherlands and the UK. Adult patients with Crohn's disease of the terminal ileum who failed >3 months of conventional immunomodulators or steroids without signs of critical strictures were randomised to laparoscopic ileocaecal resection or infliximab. Outcome measures included quality-adjusted life-years (QALYs) based on the EuroQol (EQ) 5D-3L Questionnaire and the Inflammatory Bowel Disease Questionnaire (IBDQ). Costs were measured from a societal perspective. Analyses were performed according to the intention-to-treat principle. Missing cost and effect data were imputed using multiple imputation. Cost-effectiveness planes and cost-effectiveness acceptability curves were estimated to show uncertainty.

Results

In total, 143 patients were randomised. Mean Crohn's disease total direct healthcare costs per patient at 1 year were lower in the resection group compared with the infliximab group (mean difference –8931; 95% CI –12 087 to –5097). Total societal costs in the resection group were lower than in the infliximab group, however not statistically significant (mean difference –5729, 95% CI –10 606 to 172). The probability of resection being cost-effective compared with infliximab was 0.96 at a willingness to pay (WTP) of 0 per QALY gained and per point improvement in IBDQ Score. This probability increased to 0.98 at a WTP of 20 000/QALY gained and 0.99 at a WTP of 500/point of improvement in IBDQ Score.

Conclusion

Laparoscopic ileocaecal resection is a cost-effective treatment option compared with infliximab.

Clinical trial registration number

Dutch Trial Registry NTR1150; EudraCT number 2007-005042-20 (closed on 14 October 2015).



http://bit.ly/2D2Skqo

Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA

Here we describe a protocol for the generation of cationic nanoliposomes, which is based on the dry-film method and can be used for the safe and efficient delivery of in vitro transcribed messenger RNA.

http://bit.ly/2MJ7tBp

Cancers, Vol. 11, Pages 170: Integrating Small Animal Irradiators withFunctional Imaging for Advanced Preclinical Radiotherapy Research

Cancers, Vol. 11, Pages 170: Integrating Small Animal Irradiators withFunctional Imaging for Advanced Preclinical Radiotherapy Research

Cancers doi: 10.3390/cancers11020170

Authors: Ghita Brown Kelada Graves Butterworth

Translational research aims to provide direct support for advancing novel treatment approaches in oncology towards improving patient outcomes. Preclinical studies have a central role in this process and the ability to accurately model biological and physical aspects of the clinical scenario in radiation oncology is critical to translational success. The use of small animal irradiators with disease relevant mouse models and advanced in vivo imaging approaches offers unique possibilities to interrogate the radiotherapy response of tumors and normal tissues with high potential to translate to improvements in clinical outcomes. The present review highlights the current technology and applications of small animal irradiators, and explores how these can be combined with molecular and functional imaging in advanced preclinical radiotherapy research.



http://bit.ly/2TrtozM

Cancers, Vol. 11, Pages 171: Antimicrobial Peptide TP4 Induces ROS-Mediated Necrosis by Triggering Mitochondrial Dysfunction in Wild-Type and Mutant p53 Glioblastoma Cells

Cancers, Vol. 11, Pages 171: Antimicrobial Peptide TP4 Induces ROS-Mediated Necrosis by Triggering Mitochondrial Dysfunction in Wild-Type and Mutant p53 Glioblastoma Cells

Cancers doi: 10.3390/cancers11020171

Authors: Su Pan Chen

Antimicrobial peptide tilapia piscidin 4 (TP4) from Oreochromis niloticus exhibits potent bactericidal and anti-tumorigenic effects. In a variety of cancers, the mutation status of p53 is a decisive factor for therapeutic sensitivity. Therefore, we investigated the impact of p53 status on TP4-induced cytotoxicity in glioblastoma cell lines and the molecular mechanisms that govern cytotoxic effects. Both U87MG (wild-type/WT p53) and U251 (mutant p53) glioblastoma cell lines were sensitive to TP4-induced cytotoxicity. The necrosis inhibitors Necrostatin-1 and GSK&rsquo;872 attenuated TP4-induced cytotoxicity, and TP4 treatment induced the release of cyclophilin A, a biomarker of necrosis. Moreover, TP4 induced mitochondrial hyperpolarization and dysfunction, which preceded the elevation of intracellular reactive oxygen species, DNA damage, and necrotic cell death in both U87MG and U251 glioblastoma cells. p38 was also activated by TP4, but did not contribute to cytotoxicity. SB202190, a specific p38 inhibitor, enhanced TP4-induced oxidative stress, mitochondrial dysfunction, and cytotoxicity, suggesting a protective role of p38. Furthermore, TP4-induced cytotoxicity, oxidative stress, phosphorylation of p38, and DNA damage were all attenuated by the mitochondrial-targeted reactive oxygen species (ROS) scavenger MitoTEMPO, or the reactive oxygen species scavenger N-acetyl-L-cysteine. Based on these data, we conclude that TP4 induces necrosis in both WT and mutant p53 glioblastoma cells through a mitochondrial ROS-dependent pathway.



http://bit.ly/2BgDlsE

Cancers, Vol. 11, Pages 173: Association between Paclitaxel Clearance and Tumor Response in Patients with Esophageal Cancer

Cancers, Vol. 11, Pages 173: Association between Paclitaxel Clearance and Tumor Response in Patients with Esophageal Cancer

Cancers doi: 10.3390/cancers11020173

Authors: Eelke L.A. Toxopeus Femke M. de Man Nanda Krak Katharina Biermann Annemieke J.M. Nieuweboer Lena E. Friberg Esther Oomen-de Hoop Jan J.B. van Lanschot Joel Shapiro Bas P.L. Wijnhoven Ron H.J. Mathijssen

Inter-individual variability in paclitaxel pharmacokinetics may play a role in the response to chemotherapy. Therefore, we studied the association between paclitaxel clearance and treatment response in patients with esophageal cancer. All patients who received paclitaxel (plus carboplatin) treatment for esophageal cancer between 2007 and 2013 were included. The treatment was given as neoadjuvant chemoradiotherapy (nCRT), induction chemotherapy (iCT), or palliative chemotherapy (pCT). The treatment response was assessed by the tumor regression grade (TRG) or by the RECIST1.1 criteria, respectively. The unbound paclitaxel clearance (CL) was estimated with NONMEM. The log-transformed clearance was related to response with ANOVA and independent sample t-tests. A total of 166 patients were included, of whom 113 received nCRT, 23 iCT and 30 pCT. In patients receiving nCRT, paclitaxel clearance was not associated with tumor regression grade (p-value = 0.25), nor with pathologically complete response (geometric mean 561.6 L/h) and residual disease (geometric mean 566.1 L/h, p-value = 0.90). In patients who underwent iCT or pCT, also no association between paclitaxel clearance and RECIST outcome was identified (iCT: p-value = 0.08 and pCT: p-value = 0.81, respectively). In conclusion, systemic paclitaxel exposure was not associated with response to common paclitaxel-based treatment regimens for esophageal cancer. Future studies should focus on tumor exposure in relation to systemic exposure and treatment outcome.



http://bit.ly/2TsCv3k

Whole-genome sequencing identifies complex contributions to genetic risk by variants in genes causing monogenic systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE, OMIM 152700) is a systemic autoimmune disease with a complex etiology. The mode of inheritance of the genetic risk beyond familial SLE cases is currently unknown. Additionally, the contribution of heterozygous variants in genes known to cause monogenic SLE is not fully understood. Whole-genome sequencing of DNA samples from 71 Swedish patients with SLE and their healthy biological parents was performed to investigate the general genetic risk of SLE using known SLE GWAS risk loci identified using the ImmunoChip, variants in genes associated to monogenic SLE, and the mode of inheritance of SLE risk alleles in these families. A random forest model for predicting genetic risk for SLE showed that the SLE risk variants were mainly inherited from one of the parents. In the 71 patients, we detected a significant enrichment of ultra-rare ( ≤ 0.1%) missense and nonsense mutations in 22 genes known to cause monogenic forms of SLE. We identified one previously reported homozygous nonsense mutation in the C1QC (Complement C1q C Chain) gene, which explains the immunodeficiency and severe SLE phenotype of that patient. We also identified seven ultra-rare, coding heterozygous variants in five genes (C1S, DNASE1L3, DNASE1, IFIH1, and RNASEH2A) involved in monogenic SLE. Our findings indicate a complex contribution to the overall genetic risk of SLE by rare variants in genes associated with monogenic forms of SLE. The rare variants were inherited from the other parent than the one who passed on the more common risk variants leading to an increased genetic burden for SLE in the child. Higher frequency SLE risk variants are mostly passed from one of the parents to the offspring affected with SLE. In contrast, the other parent, in seven cases, contributed heterozygous rare variants in genes associated with monogenic forms of SLE, suggesting a larger impact of rare variants in SLE than hitherto reported.



http://bit.ly/2UwXAJZ

Electrical Impedance Tomography Can Identify Ventilation and Perfusion Defects: A Neonatal Case

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 3, Page 384-386, February 1, 2019.


http://bit.ly/2Ts0mzU

Activin Type II Receptor Blockade for Treatment of Muscle Depletion in Chronic Obstructive Pulmonary Disease. A Randomized Trial

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 3, Page 313-320, February 1, 2019.


http://bit.ly/2Be3f0k

Pharmacologic Exhaustion of Suppressor Cells with Tasquinimod Enhances Bacterial Clearance during Tuberculosis

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 3, Page 386-389, February 1, 2019.


http://bit.ly/2Ts1TGf

Taking Precise Aim at Lung Disease

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 3, Page 255-256, February 1, 2019.


http://bit.ly/2BeNwhj

Imaging Advances in Chronic Obstructive Pulmonary Disease. Insights from the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) Study

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 3, Page 286-301, February 1, 2019.


http://bit.ly/2TlK4Zr

Different Background, Short Duration, and Inappropriate Participants May Harm Your Conclusion

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 3, Page 389-390, February 1, 2019.


http://bit.ly/2TsnT3F

Physiological Markers for Acute Respiratory Distress Syndrome: Let’s Get More Efficient!

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 3, Page 260-261, February 1, 2019.


http://bit.ly/2Be2Z1m

Obstructive Sleep Apnea and Cardiovascular Disease

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 3, Page 377-379, February 1, 2019.


http://bit.ly/2BbEy4w

Home Oxygen Therapy for Children. An Official American Thoracic Society Clinical Practice Guideline

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 3, Page e5-e23, February 1, 2019.


http://bit.ly/2TlJYB3

Chronic Obstructive Pulmonary Disease: Shifting the Paradigm to the Vasculature

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 3, Page 258-259, February 1, 2019.


http://bit.ly/2BfPu17

Oxygen Therapy for Children

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 3, Page P5-P6, February 1, 2019.


http://bit.ly/2Tv1fYM

Solid Fuel Use and Risks of Respiratory Diseases. A Cohort Study of 280,000 Chinese Never-Smokers

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 3, Page 352-361, February 1, 2019.


http://bit.ly/2BaGp9B

Is Cystic Fibrosis–related Diabetes Reversible? New Data on CFTR Potentiation and Insulin Secretion

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 3, Page 261-263, February 1, 2019.


http://bit.ly/2TlJMSl

Reply to Moitra et al.: Individual Chronotype May Confound Asthma Symptoms and Therapy

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 3, Page 392-394, February 1, 2019.


http://bit.ly/2BgCbxh

Reply to Lan and Shi: Different Background, Short Duration, and Inappropriate Participants May Harm Your Conclusion

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 3, Page 390-392, February 1, 2019.


http://bit.ly/2TpBHvR

Impaired Cytomegalovirus Immunity in Idiopathic Pulmonary Fibrosis Lung Transplant Recipients with Short Telomeres

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 3, Page 362-376, February 1, 2019.


http://bit.ly/2BixXW1

Sudden Death due to Complete Airway Obstruction by Bronchial Casts

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 3, Page 380-380, February 1, 2019.


http://bit.ly/2Tpktik

Club Cell Secretory Protein Deficiency Leads to Altered Lung Function

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 3, Page 302-312, February 1, 2019.


http://bit.ly/2BeNmqd

Endobronchial Ultrasound Elastography Helps Identify Fibrotic Lymph Nodes in Sarcoidosis

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 3, Page e24-e25, February 1, 2019.


http://bit.ly/2TpqdIT

New Research From Clinical Psychological Science

Personality in a Hierarchical Model of Psychopathology
Thomas A. Widiger, Martin Sellbom, Michael Chmielewski, Lee Anna Clark, Colin G. DeYoung, Roman Kotov, Robert F. Krueger, Donald R. Lynam, Joshua D. Miller, Stephanie Mullins-Sweatt, Douglas B. Samuel, Susan C. South, Jennifer L. Tackett, Katherine M. Thomas, David Watson, and Aidan G. C. Wright

Traditional classifications of psychopathology (e.g., the Diagnostic and Statistical Manual of Mental Disorders, or DSM) categorize different combinations of symptoms onto syndromes and suggest treatments for each syndrome. The Hierarchical Taxonomy of Psychopathology (HiTOP) is an alternative that considers different domains of psychopathology (e.g., internalizing, detachment) that derive from empirical research and thus organize psychopathology along these domains. Widiger et al. discuss the role of personality within the HiTOP. Different personality-trait configurations contribute differently to the development and evolution of psychopathology. Therefore, the structure of personality provides a fundamental base for the HiTOP, and personality should perhaps become the focus of preventive interventions, before the onset of psychopathology. Consistent with this idea, developing preventions and treatment protocols for domains of personality rather than (or in addition to) treating disorders and syndromes might contribute to improvements in quality of life and health.

Is Worse Attention a Risk Factor for or a Consequence of Depression, or Are Worse Attention and Depression Better Accounted for by Stress? A Prospective Test of Three Hypotheses
Naoise Mac Giollabhui, Thomas M. Olino, Johanna Nielsen, Lyn Y. Abramson, and Lauren B. Alloy

Impaired cognitive functioning (e.g., attention deficits) usually accompanies depression, but is it caused by depression, a cause for depression, or are both caused by a third process (e.g., stress)? For 3 years, Giollabhui et al. collected data from adolescents and their caregivers regarding depressive diagnosis, depressive symptoms, stressful life events, emotional maltreatment, and attention — sustained attention (i.e., focusing on one task for a long period of time), divided attention (i.e., focusing on two or more different tasks), selective attention (i.e., focusing on one task while ignoring distractions), and switching attention (i.e., switching back and forth between tasks). Giollabhui and colleagues found that the relationship between depression and attention is complex and not confined to depressive episodes. Only decreases in divided attention predicted future depressive symptoms, but switching attention declined before the first episode of depression and recovered after the episode. In fact, decreases in switching attention predicted increases in depressive symptoms, which in turn predicted worse selective and switching attention. Childhood stress, but not recent maltreatment, was associated with increases in depressive symptoms and decreases in switching attention. Overall, these results suggest the importance of considering the role of external risk factors that might increase depression and impaired cognition.

Social Anxiety and Social Behavior: A Test of Predictions From an Evolutionary Model
Erin B. Tone, Eddy Nahmias, Roger Bakeman, Trevor Kvaran, Sarah F. Brosnan, Negar Fani, and Elizabeth A. Schroth

How does social anxiety — fear and avoidance of social situations— influence social behavior in competitive contexts? Participants reported their social anxiety levels and completed a Prisoner's Dilemma game in which they selected whether they wanted to cooperate with or defect from a coplayer. The coplayer, which was always a computer, although participants were informed of it only in some of the trials, used an algorithm to decide whether to cooperate or defect. Afterward, participants reported their experiences and their goals during the game. Participants with higher social anxiety reported (a) more competitive goals than cooperative or individualistic goals and (b) greater nervousness and anger toward the coplayer during the game. Participants with higher social anxiety also tended to defect after the coplayer was cooperative. So, social anxiety predicted a tendency to respond aversively to positive behavior from others. This tendency may reflect self-protection and a lack of trust in others or an unwillingness to reciprocate positive behavior.



http://bit.ly/2UyBGG2

Correction to: Voluntary and electrically-induced muscle fatigue differently affect postural control mechanisms in unipedal stance

In the metadata of the original publication of the article.



http://bit.ly/2BdKc6a

Prevalence of germline mutations in the TP53 gene in patients with early-onset breast cancer in the Mexican population

Abstract

Background

Heterozygous germline TP53 gene mutations result in Li-Fraumeni Syndrome (LFS). Breast cancer (BC) is the most frequent tumor in young women with LFS. An important issue related to BC in the Mexican population is the average age at diagnosis, which is approximately 11 years younger than that of patients in the United States (U.S.) and Europe. The aim of this study was to determine the prevalence of germline mutations in TP53 among young Mexican BC patients.

Methods

We searched for germline mutations in the TP53 gene using targeted next-generation sequencing (NGS) in 78 BC patients younger than 45 years old (yo) who tested negative for BRCA1/2 mutations. A group of 509 Mexican women aged 45yo or older without personal or family BC history (parents/grandparents) was used as a control.

Results

We identified five patients with pathogenic variants in the TP53 gene, equivalent to 6.4% (5/78). Among patients diagnosed at age 36 or younger, 9.4% (5/55) had pathogenic TP53 mutations. Three of these variants were missense mutations (c.844C > T, c.517G > A, and c.604C > T), and the other two mutations were frameshifts (c.291delC and c.273dupC) and had not been reported previously. We also identified a variant of uncertain clinical significance (VUS), c.672G > A, which causes a putative splice donor site mutation. All patients with TP53 mutations had high-grade and HER2-positive tumors. None of the 509 patients in the healthy control group had mutations in TP53.

Conclusions

Among Mexican BC patients diagnosed at a young age, we identified a high proportion with germline mutations in the TP53 gene. All patients with the TP53 mutations had a family history suggestive of LFS. To establish the clinical significance of the VUS found, additional studies are needed. Pathogenic variants of TP53 may explain a substantial fraction of BC in young women in the Mexican population. Importantly, none of these mutations or other pathological variants in TP53 were found in the healthy control group.



http://bit.ly/2SdjO6n

Predictors for use of psychosocial services in patients with metastatic colorectal cancer receiving first line systemic treatment

Abstract

Background

Patients with advanced disease experience high levels of psychological distress, yet there is low uptake of psychosocial services offered to patients who screened positive for distress. In this study we aimed to identify predictors for use of psychosocial services in patients with metastatic colorectal cancer (mCRC) receiving first line chemotherapy enrolled in a prospective cluster randomized trial (CRT).

Methods

Patients completed measures on psychological distress, physical distress, and quality of life at baseline. Demographics, clinical characteristics at baseline and clinical events during treatment (e.g. severe adverse events, clinical benefit) were extracted from patient records. Patients reported psychosocial service utilization in- and outside the hospital after 10, 24 and 48 weeks of treatment. Multivariable logistic regression models were used to identify predictors for the use of psychosocial services.

Results

Out of 349 patients, seventy patients (20.0%) used psychosocial support services during the follow-up period. Use of psychosocial services was associated with younger age, a higher educational level, presence of more pain (at baseline), and the expressed need to talk to a professional (at baseline). In addition, patients without progressive disease within the first ten weeks of treatment were more likely to use psychosocial services .

Conclusions

One in five patients with mCRC receiving first line palliative treatment used psychosocial services during this prospective longitudinal CRT. Sociodemographic factors (age, education), clinical factors (pain and no progressive disease) and the expressed need to talk to a professional predicted use of psychosocial services. Identification of these predictors may contribute to the understanding of factors that determine the need for psychosocial services.

Trial registration

Netherlands Trial Register NTR4034.



http://bit.ly/2SmbbX8

Intraosseous synovial sarcoma of the distal ulna: a case report and review of the literature

Abstract

Background

Synovial sarcoma is a relatively rare type of soft tissue sarcoma. The commonly observed symptom is a deep-seated palpable mass accompanied by pain or tenderness. Thus, it is considered a soft tissue sarcoma and rarely occurs primarily in bone. However, only few studies have been reported on intraosseous synovial sarcoma, and reports on cases with cytogenetic or molecular confirmation are even rarer. We report a case of intraosseous synovial sarcoma of the distal ulna that has been confirmed using histopathological examination and molecular analysis.

Case presentation

A 77-year-old female was referred to our hospital with a 1-month history of right wrist pain after housework. Clinical and imaging findings suggested a benign bone tumor that was enhanced by Gd-DTPA. It was thought that the tumor was possibly an enchondroma. Initially, we planned to evaluate the benignancy of the tumor with intraoperative frozen section, followed by curettage and bone graft at one stage However, when considering carefully, characteristics of the tumor did not perfectly match those of any diagnostic categories including enchondroma. Therefore, an incisional biopsy was performed and revealed that the tumor was synovial sarcoma. Following an elaborate plan, the patient underwent a wide resection of the tumor at the distal part of the right ulna. Reverse transcription-polymerase chain reaction (RT-PCR) from the resected specimen and sequencing of RT-PCR products demonstrated a chimeric SYT-SSX1 transcript, confirming the diagnosis of synovial sarcoma.

Conclusions

Synovial sarcoma is seldom considered in differential diagnosis of bone tumors because it is difficult to line up such an unusual diagnosis as a differential diagnosis. When the lesion does not perfectly fit into any diagnostic category, when the initial image diagnosis appears unconvincing, biopsy and pathology are indicated, recalling Jaffe's triangle. According to these diagnostic processes, the patient successfully completed the treatment for this rare intraosseous synovial sarcoma, following a careful plan based on the preoperative diagnosis.



http://bit.ly/2CYGgGH

Landscape of germline and somatic mitochondrial DNA mutations in pediatric malignancies

Little is known about the spectrum of mitochondrial DNA (mtDNA) mutations across pediatric malignancies. In this study, we analyzed matched tumor and normal whole genome sequencing data from 616 pediatric patients with hematopoietic malignancies, solid tumors, and brain tumors. We identified 391 mtDNA mutations in 284 tumors including 45 loss-of-function mutations, which clustered at 4 statistically significant hotspots in MT-COX3, MT-ND4, and MT-ND5, and at a mutation hotspot in MT-tRNA-MET. A skewed ratio (4.83) of non-synonymous versus synonymous (dN/dS) mtDNA mutations with high statistical significance was identified based on Monte Carlo simulations in the tumors. By comparison, opposite ratios of 0.44 and 0.93 were observed in 616 matched normal tissues and in 249 blood samples from children without cancer, respectively. mtDNA mutations varied by cancer type and mtDNA haplogroup. Collectively, these results suggest that deleterious mtDNA mutations play a role in the development and progression of pediatric cancers.

http://bit.ly/2SfJ5gd

CCL27/CCL28-CCR10 CHEMOKINE SIGNALING MEDIATES MIGRATION OF LYMPHATIC ENDOTHELIAL CELLS

The formation of new lymphatic vessels (lymphangiogenesis) and remodeling of existing lymphatics are thought to facilitate the entry and transport of tumor cells into lymphatic vessels and on to distant organs. The migration of lymphatic endothelial cells (LEC) toward guidance cues is critical for lymphangiogenesis. While chemokines are known to provide directional navigation for migrating immune cells, their role in mediating LEC migration during tumor-associated lymphangiogenesis is not well defined. Here we undertook gene profiling studies to identify chemokine-chemokine receptor pairs that are involved in tumor lymphangiogenesis associated with lymph node metastasis. CCL27 and CCL28 were expressed in tumor cells with metastatic potential, while their cognate receptor, CCR10, was expressed by LEC and upregulated by the lymphangiogenic growth factor VEGF-D and the pro-inflammatory cytokine TNF-α. LEC were attracted to both CCL27 and CCL28 in a CCR10-dependent manner. Abnormal lymphatic vessel patterning in CCR10-deficient mice confirmed the role of CCR10 in lymphatic patterning. In vivo analyses showed that LEC are recruited to a CCL27 or CCL28 source, while VEGF-D was required in combination with these chemokines to enable formation of coherent lymphatic vessels. Moreover, tumor xenograft experiments demonstrated that even though CCL27 expression by tumors enhanced LEC recruitment, the ability to metastasize was dependent on the expression of VEGF-D. These studies demonstrate that CCL27 and CCL28 act through CCR10 to cooperate with inflammatory mediators and VEGF-D during tumor lymphangiogenesis.

http://bit.ly/2GmbOtt

Transcriptome-wide association study identifies new candidate susceptibility genes for glioma

Genome-wide association studies (GWAS) have so far identified 25 loci associated with glioma risk, with most showing specificity for either glioblastoma (GBM) or non-GBM tumors. The majority of these GWAS susceptibility variants reside in non-coding regions and the causal genes underlying the associations are largely unknown. Here we performed a transcriptome-wide association study to search for novel risk loci and candidate causal genes at known GWAS loci using Genotype-Tissue Expression Project (GTEx) data to predict cis-predicted gene expression in relation to GBM and non-GBM risk in conjunction with GWAS summary statistics on 12,488 glioma cases (6,183 GBM, 5,820 non-GBM) and 18,169 controls. Imposing a Bonferroni-corrected significance level of P<5.69×10-6, we identified 31 genes, including GALNT6 at 12q13.33, as a candidate novel risk locus for GBM (mean Z=4.43, P=5.68×10-6). GALNT6 resides at least 55 Mb away from any previously-identified glioma risk variant, while all other 30 significantly-associated genes were located within 1 Mb of known GWAS-identified loci and were not significant after conditioning on the known GWAS-identified variants. These data identify a novel locus (GALNT6 at 12q13.33) and 30 genes at 12 known glioma risk loci associated with glioma risk, providing further insights into glioma tumorigenesis.

http://bit.ly/2SfIxa9

The deubiquitylase OTUB1 mediates ferroptosis via stabilization of SCL7A11

Although cell cycle arrest, senescence, and apoptosis are established mechanisms of tumor suppression, accumulating evidence reveals that ferroptosis, an iron-dependent, non-apoptotic form of cell death, represents a new regulatory pathway in suppressing tumor development. Ferroptosis is triggered by lipid peroxidation and is tightly regulated by SLC7A11, a key component of the cystine-glutamate antiporter. Although many studies demonstrate the importance of transcriptional regulation of SLC7A11 in ferroptotic responses, it remains largely unknown how the stability of SLC7A11 is controlled in human cancers. In this study, we utilized biochemial purification to identify the ubiquitin hydrolase OTUB1 as a key factor in modulating SLC7A11 stability. OTUB1 directly interacted with and stabilized SLC7A11; conversely, OTUB1 knockdown diminished SLC7A11 levels in cancer cells. OTUB1 was overexpressed in human cancers, and inactivation of OTUB1 destabilized SLC7A11 and led to growth suppression of tumor xenografts in mice, which was associated with reduced activation of ferroptosis. Notably, overexpression of the cancer stem cell marker CD44 enhanced the stability of SLC7A11 by promoting the interaction between SLC7A11 and OTUB1; depletion of CD44 partially abrogated this interaction. CD44 expression suppressed ferroptosis in cancer cells in an OTUB1-dependent manner. Together, these results show that OTUB1 plays an essential role in controlling the stability of SLC7A11 and the CD44-mediated effects on ferroptosis in human cancers.

http://bit.ly/2GmbFWX

Eomes+T-betlow CD8+ T cells are functionally impaired and are associated with poor clinical outcome in patients with acute myeloid leukemia (AML)

Acute myeloid leukemia (AML) is a devastating blood cancer with poor prognosis. Immunotherapy targeting inhibitory pathways to unleash the anti-leukemia T cell response is a promising strategy for the treatment of leukemia, but we must first understand the underlying molecular mechanisms. Eomesodermin (Eomes) and T-bet are both T-box transcription factors that regulate CD8+ T cell responses in a context-specific manner. Here we examined the role of these transcription factors in CD8+ T cell immunity in AML patients. We report that the frequency of Eomes+T-betlow CD8+ T cells increased in newly diagnosed AML. This cell subset produced less cytokines and displayed reduced killing capacity, whereas depletion of Eomes by siRNA reversed these functional defects. Furthermore, Eomes bound the promoter of T cell immunoglobulin and ITIM domain (TIGIT) and positively regulated the expression of this inhibitory receptor on patient-derived T cells. A high frequency of Eomes+T-betlow CD8+ T cells was associated with poor response to induction chemotherapy and shorter overall survival in AML patients. These findings have significant clinical implications as they not only identify a predictive and prognostic biomarker for AML, but they also provide an important target for effective leukemia therapeutics.

http://bit.ly/2SfIqLL

Intracellular C3 Protects Human Airway Epithelial Cells from Stress-associated Cell Death

American Journal of Respiratory Cell and Molecular Biology, Volume 60, Issue 2, Page 144-157, February 2019.


http://bit.ly/2S5Z8Ot

IL-9 Blockade Suppresses Silica-induced Lung Inflammation and Fibrosis in Mice

American Journal of Respiratory Cell and Molecular Biology, Volume 60, Issue 2, Page 232-243, February 2019.


http://bit.ly/2Uww3rZ

Lung Microbiome Is Influenced by the Environment and Asthmatic Status in an Equine Model of Asthma

American Journal of Respiratory Cell and Molecular Biology, Volume 60, Issue 2, Page 189-197, February 2019.


http://bit.ly/2S1Yul0

Dusting Off IL-9 as a New Therapeutic Target for Pulmonary Fibrosis

American Journal of Respiratory Cell and Molecular Biology, Volume 60, Issue 2, Page 141-143, February 2019.


http://bit.ly/2UB7udE

P311 in Scar Wars: Myofibroblasts Lost without Transforming Growth Factor β Translation

American Journal of Respiratory Cell and Molecular Biology, Volume 60, Issue 2, Page 139-140, February 2019.


http://bit.ly/2S5Z9C1

Impairment of Fatty Acid Oxidation in Alveolar Epithelial Cells Mediates Acute Lung Injury

American Journal of Respiratory Cell and Molecular Biology, Volume 60, Issue 2, Page 167-178, February 2019.


http://bit.ly/2UzX5Pj

Intercellular Communication between Airway Epithelial Cells Is Mediated by Exosome-Like Vesicles

American Journal of Respiratory Cell and Molecular Biology, Volume 60, Issue 2, Page 209-220, February 2019.


http://bit.ly/2S0qt4m

Alveolar Epithelial Cells Burn Fat to Survive Acute Lung Injury

American Journal of Respiratory Cell and Molecular Biology, Volume 60, Issue 2, Page 135-136, February 2019.


http://bit.ly/2UsOfCW

AMP Kinase Activation Attenuates Cardiac Remodeling in Pulmonary Hypertension due to Heart Failure with Preserved Ejection Fraction; Lung Epithelial Progenitor Cells in Alveolar Regeneration; and Drug Discovery and Novel Therapies for Lung Cancer

American Journal of Respiratory Cell and Molecular Biology, Volume 60, Issue 2, Page 244-247, February 2019.


http://bit.ly/2UyMrIq

P311 Promotes Lung Fibrosis via Stimulation of Transforming Growth Factor-β1, -β2, and -β3 Translation

American Journal of Respiratory Cell and Molecular Biology, Volume 60, Issue 2, Page 221-231, February 2019.


http://bit.ly/2S2OpUP