bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Mitochondrial Genetics on the Mitochondrial Toxicity of Linezolid in Blood Cells and Skin Nerve Fibers
Authors: Garrabou G. , Soriano À. , Pinós T. , Casanova-Mollà J. , Pacheu-Grau D. , Morén C. , García-Arumí E. , Morales M. , Ruiz-Pesini E. , Catalán-Garcia M. , Milisenda J. C. , Lozano E. , Andreu A. L. , Montoya J. , Mensa J. , Cardellach F.
Published: July 2017

The antibiotic linezolid is a ribosomal inhibitor with excellent efficacy. Although the administration period has been reduced to 28 days, side effects, usually of hematologic or neuropathic origin, are still reported due to secondary inhibition of mitochondrial protein synthesis. Susceptibility to linezolid toxicity remains unknown. Therefore, the objective of this study was to gain an understanding of clinical heterogeneity in response to identical linezolid exposures through exhaustive examination of the molecular basis of tissue-dependent mitotoxicity, consequent cell dysfunction, and the association of mitochondrial genetics with adverse effects of linezolid administered for the recommended period. Peripheral blood mononuclear cells (PBMC) and skin nerve fibers from 19 and 6 patients, respectively, were evaluated before and after a 28-day linezolid treatment in order to assess toxic effects on mitochondria and cells. Mitochondrial DNA haplotypes and single nucleotide polymorphisms (SNPs) in ribosomal sequences where linezolid binds to mitochondrial ribosomes were also analyzed to investigate their genetic contributions. We found that linezolid reduced mitochondrial protein levels, complex IV activity, and mitochondrial mass in PBMC and was associated with a trend toward an increase in the rate of apoptosis. In skin tissue, mitochondrial mass increased within nerve fibers, accompanied by subclinical axonal swelling. Mitochondrial haplogroup U, mutations in 12S rRNA, and the m.2706A→G, m.3197T→C, and m.3010G→A polymorphisms in 16S rRNA showed a trend toward an association with increased mitochondrial and clinical adverse effects. We conclude that even when linezolid is administered for a shorter time than formerly, adverse effects are reported by 63% of patients. Linezolid exerts tissue-dependent mitotoxicity that is responsible for downstream cellular consequences (blood cell death and nerve fiber swelling), leading to adverse hematologic and peripheral nervous side effects. Multicentric studies should confirm genetic susceptibility in larger cohorts.
OXA-244-Producing Escherichia coli Isolates, a Challenge for Clinical Microbiology Laboratories
Authors: Hoyos-Mallecot Yannick , Naas Thierry , Bonnin Rémy A. , Patino Rafael , Glaser Philippe , Fortineau Nicolas , Dortet Laurent
Published: July 2017

OXA-244 is a single-point-mutant derivative of OXA-48 displaying reduced carbapenemase activity. Here, we report the microbiological features of seven OXA-244-producing
Escherichia coli
isolates. Only one isolate grew on ChromID Carba Smart medium (bioMérieux), but six of the seven isolates grew on ChromID extended-spectrum-β-lactamase (ESBL) medium (bioMérieux), as they coproduced an ESBL and/or a plasmid-encoded cephalosporinase. The production of a carbapenemase was detected in 57.1%, 71.4%, 71.4%, and 100% of the
E. coli
isolates using the Carba NP test, the Rapidec Carba NP test (bioMérieux), a matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) hydrolysis assay (Bruker), and the OXA-48 K-SeT assay (Coris BioConcept), respectively. Our results indicate that OXA-244-producing
E. coli
isolates are difficult to detect, which may lead to their silent spread.
Antibody-Mediated Catalysis in Infection and Immunity
Authors: Bowen Anthony , Wear Maggie , Casadevall Arturo
Published: July 2017

The existence of catalytic antibodies has been known for decades. Natural antibodies capable of cleaving nucleic acid, protein, and polysaccharide substrates have been described. Although the discovery of catalytic antibodies initially aroused great interest because of their promise for the development of new catalysts, their enzymatic performance has been disappointing due to low reaction rates. However, in the areas of infection and immunity, where processes often occur over much longer times and involve high antibody concentrations, even low catalytic rates have the potential to influence biological outcomes. In this regard, the presence of catalytic antibodies recognizing host antigens has been associated with several autoimmune diseases. Furthermore, naturally occurring catalytic antibodies to microbial determinants have been correlated with resistance to infection. Recently, there has been substantial interest in harnessing the power of antibody-mediated catalysis against microbial antigens for host defense. Additional work is needed, however, to better understand the prevalence, function, and structural basis of catalytic activity in antibodies. Here we review the available information and suggest that antibody-mediated catalysis is a fertile area for study with broad applications in infection and immunity.
Serum androgen levels and their relation to performance in track and field: mass spectrometry results from 2127 observations in male and female elite athletes
Authors: Bermon Stéphane , Garnier Pierre-Yves
Published: July 2017

Objective

To describe and characterise serum androgen levels and to study their possible influence on athletic performance in male and female elite athletes.

Methods

2127 observations of competition best performances and mass spectrometry-measured serum androgen concentrations, obtained during the 2011 and 2013 International Association of Athletics Federations World Championships, were analysed in male and female elite track and field athletes. To test the influence of serum androgen levels on performance, male and female athletes were classified in tertiles according to their free testosterone (fT) concentration and the best competition results achieved in the highest and lowest fT tertiles were then compared.

Results

The type of athletic event did not influence fT concentration among elite women, whereas male sprinters showed higher values for fT than male athletes in other events. Men involved in all throwing events showed significantly (p<0.05) lower testosterone and sex hormone binding globulin than men in other events. When compared with the lowest female fT tertile, women with the highest fT tertile performed significantly (p<0.05) better in 400 m, 400 m hurdles, 800 m, hammer throw, and pole vault with margins of 2.73%, 2.78%, 1.78%, 4.53%, and 2.94%, respectively. Such a pattern was not found in any of the male athletic events.

Conclusion

Female athletes with high fT levels have a significant competitive advantage over those with low fT in 400 m, 400 m hurdles, 800 m, hammer throw, and pole vault.
Healthcare professional perceptions of family-centred rounds in French NICUs: a cross-sectional study
Authors: Thébaud Véronique , Lecorguillé Marion , Roué Jean-Michel , Sizun Jacques
Published: July 2017

Objective

To assess the perceptions of healthcare professionals (HCPs) regarding parental presence at medical rounds in French neonatal intensive care units (NICUs). We hypothesised that HCPs would perceive barriers against allowing parental participation in round discussions.

Methods

This cross-sectional study approached 304 HCPs from three groups; group 1: French professionals that attended an annual French-speaking meeting of the Neonatal Individualized Developmental Care and Assessment Program (NIDCAP); group 2: NICU professionals from a tertiary care academic hospital in western France; and group 3: paediatric residents from six French universities. We invited all HCPs to complete a questionnaire about medical round practices and their perceptions towards parent participation in family-centred rounds (FCRs).

Results

Of the 176 (58%) questionnaires returned, 159 were included in the analysis. The majority of medical rounds took place at the bedside for groups 1 and 3 (68%, 95% CI 54 to 80 and 71%, 95% CI 56 to 84, respectively) and in a conference room for group 2 (65%, 95% CI 51 to 78). Overall, respondents positively perceived FCR for themselves, parents and students. However, most respondents agreed with the following claims: ‘Parental attendance at medical rounds prevents some discussions between health professionals’ (66%, 95% CI 57 to 73), ‘FCR increases round durations’ (63%,95% CI 55 to 71) and ‘Some decisions made during medical rounds may be stressful for parents’ (51%, 95% CI 42 to 59). Nevertheless, responses varied significantly according to NIDCAP training and NICU experience and consequently group 1 displayed a significantly more positive attitude than other groups (p<0.001); they expressed less concern about potentially inhibiting discussions between HCPs (p<0.001), the feasibility (p=0.02) and prolonged round durations (p<0.001). Several difficulties and facilitators of FCR implementation were variously reported, but all groups agreed that routine workload was an important difficulty and that medical leadership would be an important facilitator.

Conclusion

French HCPs expressed rather positive perceptions towards parental presence in NICU rounds. However, some concerns need to be addressed.
In utero and early childhood exposure to secondhand smoke in Taiwan: a population-based birth cohort study
Authors: Cheng Kai-Wen , Chiang Wan-Lin , Chiang Tung-Liang
Published: July 2017

Objectives

This study provides secondhand smoke (SHS) exposure data in utero and after birth when children were at 18 months, 36 months and 66 months old, and it identifies risk factors for the early childhood SHS among 18-month-old infants living in smoker and non-smoker households.

Study design

The data come from the Taiwan Birth Cohort Study, a longitudinal survey of a birth cohort born in 2005. This study used the survey wave when children were 18 months old (n=18 845) for statistical analysis of early childhood SHS exposure. Logistic regression was used to identify the risk factors of the SHS exposure.

Results

Approximately 62% of the 18-month-old infants lived in a household with at least one smoker, with the father being the smoker in 84% of those households. Among these infants living in a smoker household, 70% were exposed to SHS and 36% were exposed to heavy SHS in utero, and the prevalence was approximately 66% and 17% after birth for SHS and heavy SHS, respectively. The number and the existence of smokers in the household, parents’ smoking status, father’s educational attainment and being a first-born baby are strong predictors of early childhood heavy SHS exposure.

Conclusions

Encouraging families to have a smoke-free home environment, empowering women to ensure their perspectives and rights are embedded into tobacco control efforts and educating families about the health risks from childhood SHS exposure, especially among people living in households with smokers, will protect non-smoking adults and children from SHS exposure.
Effect of adherence to antihypertensive medication on stroke incidence in patients with hypertension: a population-based retrospective cohort study
Authors: Lee Hyo Jung , Jang Sung-In , Park Eun-Cheol
Published: July 2017

Objective

High blood pressure is a modifiable risk factor for stroke, but non-adherence to antihypertensive medication is a growing concern for healthcare providers in controlling blood pressure. This study aimed to investigate the effect of adherence to antihypertensive medication on stroke incidence.

Design

Retrospective cohort study.

Setting

We analysed National Health Insurance claim data and check-up data from 2009 to 2013.

Participants

38520patients with hypertension were defined as those diagnosed with hypertension and prescribed antihypertensive medication.

Interventions

No interventions were made.

Outcome measure

Poisson regression analysis using generalised estimating equations models was performed to examine the association between adherence to antihypertensive medication and stroke incidence.

Results

Among 38 520 patients with hypertension, 957 (2.5%) strokes occurred during the study period. Non-adherence to medication was significantly associated with a higher risk of stroke (intermediate adherence: adjusted relative risk (aRR)=1.13, 95% CI=1.06 to 1.21; poor adherence: aRR=1.27, 95% CI=1.17 to 1.38).

Conclusions

Non-adherence to antihypertensive medication in patients with hypertension was associated with an increased risk of stroke. Therefore, healthcare providers need to focus on interventional strategies to ensure that these patients adhere to medication therapy and to provide continuing support to achieve long-term adherence, ultimately minimising negative health outcomes.
Test accuracy of drug and antibody assays for predicting response to antitumour necrosis factor treatment in Crohn’s disease: a systematic review and meta-analysis
Authors: Freeman Karoline , Taylor-Phillips Sian , Connock Martin , Court Rachel , Tsertsvadze Alexander , Shyangdan Deepson , Auguste Peter , Mistry Hema , Arasaradnam Ramesh , Sutcliffe Paul , Clarke Aileen
Published: July 2017

Objective

To present meta-analytic test accuracy estimates of levels of antitumour necrosis factor (anti-TNF) and antibodies to anti-TNF to predict loss of response or lack of regaining response in patients with anti-TNF managed Crohn’s disease.

Methods

MEDLINE, Embase, the Cochrane Library and Science Citation Index were searched from inception to October/November 2014 to identify studies which reported 2×2 table data of the association between levels of anti-TNF or its antibodies and clinical status. Hierarchical/bivariate meta-analysis was undertaken with the user-written ‘metandi’ package of Harbord and Whiting using Stata V.11 software, for infliximab, adalimumab,anti-infliximab and anti-adalimumab levels as predictors of loss of response. Prevalence of Crohn’s disease in included studies was meta-analysed using a random effects model in MetaAnalyst software to calculate positive and negative predictive values. The search was updated in January 2017.

Results

31 studies were included in the review. Studies were heterogeneous with respect to the type of test used, criteria for establishing response and loss of response, population examined and results. Meta-analytic summary point estimates for sensitivity and specificity were 65.7% and 80.6% for infliximab trough levels and 56% and 79% for antibodies to infliximab, respectively. Pooled results for adalimumab trough levels and antibodies to adalimumab were similar. Pooled positive and negative predictive values ranged between 70% and 80% implying that between 20% and 30% of both positive and negative test results may be incorrect in predicting loss of response.

Conclusion

The available evidence suggests that these tests have modest predictive accuracy for clinical status; direct test accuracy comparisons in the same population are needed. More clinical trial evidence from test–treat studies is required before the clinical utility of the tests can be reliably evaluated.
Mechanism evaluation of a lifestyle intervention for patients with musculoskeletal pain who are overweight or obese: protocol for a causal mediation analysis
Authors: Lee Hopin , Wiggers John , Kamper Steven J , Williams Amanda , O'Brien Kate M , Hodder Rebecca K , Wolfenden Luke , Yoong Sze Lin , Campbell Elizabeth , Haskins Robin , Robson Emma K , McAuley James H , Williams Christopher M
Published: July 2017

Introduction

Low back pain (LBP) and knee osteoarthritis (OA) are highly prevalent and disabling conditions that cause societal and economic impact worldwide. Two randomised controlled trials (RCTs) will evaluate the effectiveness of a multicomponent lifestyle intervention for patients with LBP and knee OA who are overweight or obese. The key targets of this intervention are to improve physical activity, modify diet and correct pain beliefs. These factors may explain how a lifestyle intervention exerts its effects on key patient-relevant outcomes: pain, disability and quality of life. The aim of this protocol is to describe a planned analysis of a mechanism evaluation for a lifestyle intervention for overweight or obese patients with LBP and knee OA.

Methods and analysis

Causal mediation analyses of 2 two-armed RCTs. Both trials are part of a cohort-multiple RCT, embedded in routine health service delivery. In each respective trial, 160 patients with LBP and 120 patients with knee OA waiting for orthopaedic consultation will be randomised to a lifestyle intervention, or to remain part of the original cohort. The intervention consists of education and advice about the benefits of weight loss and physical activity, and the Australian New South Wales Get Healthy Service. All outcome measures including patient characteristics, primary and alternative mediators, outcomes, and potential confounders will be measured at baseline (T0). The primary mediator, weight, will be measured at 6 months post randomisation; alternative mediators including diet, physical activity and pain beliefs will be measured at 6 weeks post randomisation. All outcomes (pain, disability and quality of life) will be measured at 6 months post randomisation. Data will be analysed using causal mediation analysis with sensitivity analyses for sequential ignorability. All mediation models were specified a priori before completing data collection and without prior knowledge about the effectiveness of the intervention.

Ethics and dissemination

The study is approved by the Hunter New England Health Human Research Ethics Committee (13/12/11/5.18) and the University of Newcastle Human Research Ethics Committee (H-2015–0043). The results will be disseminated in peer-reviewed journals and at scientific conferences.

Trial registration number

ACTRN12615000490572 and ACTRN12615000478516; Pre-results.
Factors associated with return to work among people on work absence due to long-term neck or back pain: a narrative systematic review
Authors: Rashid Mamunur , Kristofferzon Marja-Leena , Nilsson Annika , Heiden Marina
Published: July 2017

Objective

The purpose of this narrative systematic review was to summarise prognostic factors for return to work (RTW) among people with long-term neck/shoulder or back pain.

Methods

A systematic literature search was performed through three databases (Medline, CINAHL and PsycINFO) for studies published until February 2016. Only observational studies of people on work absence (â‰¥2 weeks) due to neck/shoulder or back pain were included. The methodological quality of the included studies was assessed using guidelines for assessing quality in prognostic studies on the basis of Framework of Potential Biases. Factors found in the included studies were grouped into categories based on similarities and then labelled according to the aspects covered by the factors in the category.

Results

Nine longitudinal prospective cohort studies and one retrospective study fulfilled the inclusion criteria. From these, five categories of factors were extracted. Our findings indicate that recovery beliefs, health-related factors and work capacity are important for RTW among people with long-term neck or back pain. We did not find support for workplace factors and behaviour being predictive of RTW.

Conclusions

Our findings suggest that recovery beliefs, perceived health and work capacity may be important targets of intervention for people with long-term neck or back pain. However, more high-quality prospective studies are needed to confirm the results and improve our understanding of what is needed to facilitate RTW in this population.
Investigating the safety and activity of the use of BTT1023 (Timolumab), in the treatment of patients with primary sclerosing cholangitis (BUTEO): A single-arm, two-stage, open-label, multi-centre, phase II clinical trial protocol
Authors: Arndtz Katherine , Corrigan Margaret , Rowe Anna , Kirkham Amanda , Barton Darren , Fox Richard P , Llewellyn Laura , Athwal Amrita , Wilkhu Manpreet , Chen Yung-Yi , Weston Chris , Desai Amisha , Adams David H , Hirschfield Gideon M
Published: July 2017

Introduction

Primary sclerosing cholangitis (PSC) is a progressive inflammatory liver disease characterised by relentless liver fibrosis and a high unmet need for new therapies. Preventing fibrosis represents an important area of interest in the development of vital new drugs. Vascular adhesion protein-1 (VAP-1) drives inflammation in liver disease, and provision of an antibody against VAP-1 blunts fibrosis in murine models of liver injury.

Methods and analysis

BUTEO is a single-arm, two-stage, open-label, multi-centre, phase II clinical trial. Up to 59 patients will receive treatment with anti-VAP monoclonal antibody, BTT1023, over a 78-day treatment period. Adults with PSC and a serum alkaline phosphatase (ALP) of at least 1.5 times the upper limit of normal will be included. Our primary outcome measure is a reduction in ALP by >25% from baseline to Day 99. Secondary outcome measures include safety and tolerability, changes pre therapy/post therapy in circulating serum VAP-1 as well as imaging findings. The first patient participant was recruited on 08 September 2015.

Ethics and dissemination

This protocol has been approved by the Research Ethics Committee (REC, reference 14/EM/1272). The first REC approval date was 06 January 2015 with three subsequent approved amendments. This article refers to protocol V3.0, dated 16 March 2016. Results will be disseminated via peer-reviewed publication and presentation at international conferences.

Trial registration

The trial is registered with the European Medicines agency (EudraCT: 2014-002393-37), the National Institute for Health Research (Portfolio ID: 18051) and ISRCTN: 11233255. The clinicaltrials.gov identifier isNCT02239211. Pre-results.
Self-reported sleep duration and napping, cardiac risk factors and markers of subclinical vascular disease: cross-sectional study in older men
Authors: Zonoozi Shahrzad , Ramsay Sheena E , Papacosta Olia , Lennon Lucy , Ellins Elizabeth A , Halcox Julian P J , Whincup Peter H , Goya Wannamethee S
Published: July 2017

Studyobjectives

Daytime sleep has been associated with increased risk of cardiovascular disease and heart failure (HF), but the mechanisms remain unclear. We have investigated the association between daytime and night-time sleep patterns and cardiovascular risk markers in older adults including cardiac markers and subclinical markers of atherosclerosis (arterial stiffness and carotid intima-media thickness (CIMT)).

Methods

Cross-sectional study of 1722 surviving men aged 71–92 examined in 2010–2012 across 24 British towns from a prospective study initiated in 1978–1980. Participants completed a questionnaire and were invited for a physical examination. Men with a history of heart attack or HF (n=251) were excluded from the analysis.

Results

Self-reported daytime sleep duration was associated with higher fasting glucose and insulin levels (p=0.02 and p=0.01, respectively) even after adjustment for age, body mass index, physical activity and social class. Compared with those with no daytime sleep, men with daytime sleep >1 hour, defined as excessive daytime sleepiness (EDS), had a higher risk of raised N-terminal pro-brain natriuretic peptide of ≥400 pg/mL, the diagnostic threshold for HF (OR (95% CI)=1.88 (1.15 to 3.1)), higher mean troponin, reduced lung function (forced expiratory volume in 1 s) and elevated von Willebrand factor, a marker of endothelial dysfunction. However, EDS was unrelated to CIMT and arterial stiffness. By contrast, night-time sleep was only associated with HbA1c (short or long sleep) and arterial stiffness (short sleep).

Conclusions

Daytime sleep duration of >1 hour may be an early indicator of HF.
Evaluation of the Gold Coast Integrated Care for patients with chronic disease or high risk of hospitalisation through a non-randomised controlled clinical trial: a pilot study protocol
Authors: Scuffham Paul A , Mihala Gabor , Ward Lauren , McMurray Anne , Connor Martin
Published: July 2017

Introduction

Chronic diseases are the leading cause of illness, disability and death in Australia. The prevalence and associated health expenditure are projected to soar. There is no ‘whole system’ approach to healthcare in Australia. To overcome this fragmentation, the Gold Coast Hospital and Health Service (GCHHS) is developing a new model known as Gold Coast Integrated Care (GCIC). To evaluate GCIC a 4-year pilot trial commenced in March 2015. This protocol paper describes the evaluation of GCIC.

Methods and analysis

A pragmatic non-randomised controlled clinical trial is conducted to test the hypothesis that GCIC will result in improved health and well-being at no additional cost to the healthcare system. Using a mixed methods approach, impact, outcome and process evaluations will be undertaken to assess the effectiveness and acceptability, including the balance of costs between primary and public secondary care sectors, staff and training requirements, clinical service delivery, and trial implementation.

Fifteen general practices have agreed to deliver GCIC. One thousand five hundred of their adult patients with treated chronic diseases, high risk of hospitalisation or healthcare utilisation were recruited to the intervention arm. Approximately 3000 patients not associated with the participating general practices were identified as controls using propensity matching which will provide service utilisation and disease data for usual care.

Baseline data and follow-up observations are collected annually until the end of 2018. Quantitative analyses will measure patient healthcare costs, utilisation of health services, and health outcomes, and general practice clinical service delivery according to clinical guidelines (number of foot exams, HbA1c tests). Qualitative analyses will focus on patient and staff experiences, satisfaction, engagement and implementation of the programme as planned.

Ethics and dissemination

Approval was received from the GCHHS and Griffith University. The study is registered with the Australian New Zealand Clinical Trial Registry (ACTRN12616000821493). Findings will be communicated via yearly reports to funding bodies and scientific publications.

Trial registration number

ACTRN12616000821493; Pre-results.
Serum 25-hydroxyvitamin D level, chronic diseases and all-cause mortality in a population-based prospective cohort: the HUNT Study, Norway
Authors: Sun Yi-Qian , Langhammer Arnulf , Skorpen Frank , Chen Yue , Mai Xiao-Mei
Published: July 2017

Objective

To investigate the association of vitamin D status with all-cause mortality in a Norwegian population and the potential influences of existing chronic diseases on the association.

Design

A population-based prospective cohort study.

Setting

Nord-Trøndelag County, Norway.

Participants

A random sample (n=6613) of adults aged 20 years or older in a cohort.

Methods

Serum 25-hydroxyvitamin D (25(OH)D) levels were measured in blood samples collected at baseline (n=6377). Mortality was ascertained from the Norwegian National Registry. Cox regression models were applied to estimate the HRs with 95% CIs for all-cause mortality in association with serum 25(OH)D levels after adjustment for a wide spectrum of confounding factors as well as chronic diseases at baseline.

Results

The median follow-up time was 18.5 years, during which 1539 subjects died. The HRs for all-cause mortality associated with the first quartile level of 25(OH)D (<34.5 nmol/L) as compared with the fourth quartile (≥58.1 nmol/L) before and after adjustment for chronic diseases at baseline were 1.30 (95% CI 1.11 to 1.51) and 1.27 (95% CI 1.09 to 1.48), respectively. In the subjects without chronic diseases at baseline and with further exclusion of the first 3 years of follow-up, the corresponding adjusted HR was 1.34 (95% CI 1.09 to 1.66).

Conclusions

Low serum 25(OH)D level was associated with increased all-cause mortality in a general Norwegian population. The association was not notably influenced by existing chronic diseases.
Assessment of patient-reported outcome measures in pleural interventions
Authors: Psallidas Ioannis , Yousuf Ahmed , Talwar Ambika , Hallifax Rob J , Mishra Eleanor K , Corcoran John P , Ali Nabeel , Rahman Najib M
Published: July 2017

Introduction

There is a lack of data evaluating the clinical effect on symptoms of pleural intervention procedures. This has led to the development of patient-reported outcome measures (PROMs) to define what constitutes patient benefit. The primary aim of this paper was to prospectively assess the effect of pleural procedures on PROMs and investigate the relationship between symptom change and clinical factors.

Methods

We prospectively collected data as part of routine clinical care from 158 patients with pleural effusion requiring interventions. Specific questionnaires included two patient-reported scores (a seven-point Likert scale and a 100 mm visual analogue scale (VAS) to assess symptoms).

Results

Excluding diagnostic aspiration, the majority of patients (108/126, 85.7%) experienced symptomatic benefit from fluid drainage (mean VAS improvement 42.6 mm, SD 24.7, 95% CI 37.9 to 47.3). There was a correlation between symptomatic benefit and volume of fluid removed post aspiration. A negative association was identified between the number of septations seen on ultrasound and improvement in dyspnoea VAS score in patients treated with intercostal chest drain.

Conclusion

The results of our study highlight the effect of pleural interventions from a patient’s perspective. The outcomes defined have the potential to form the basis of a clinical useful tool to appraise the effect, compare the efficiency and identify the importance of pleural interventions to the patients.
Frailty and patient-reported outcomes in subjects with chronic obstructive pulmonary disease: are they independent entities?
Authors: Kusunose Masaaki , Oga Toru , Nakamura Saya , Hasegawa Yoshinori , Nishimura Koichi
Published: July 2017

Introduction

There is a hypothesis that chronic obstructive pulmonary disease (COPD) is an accelerated ageing disease. Frailty is a geriatric syndrome characterised by physical, psychological and social vulnerability, thought to be a feature of ageing. The authors aimed to explore the relationship between frailty and physiological and patient-reported outcomes (PROs) in subjects with stable COPD.

Methods

We administered the Kihon Checklist that has been validated for frailty screening. We also assessed patient-reported measurements of health status and dyspnoea using the COPD Assessment Test (CAT), the St. George’s Respiratory Questionnaire (SGRQ), the Hyland Scale, the Medical Outcomes Study 36-item short-form (SF-36), the Baseline Dyspnea Index (BDI) and the Dyspnea-12 (D-12). Pulmonary function was also measured.

Results

Of 79 consecutive COPD outpatients, 38 (48.1%), 24 (30.4%) and 17 (21.5%) patients were classified as robust, prefrail and frail, respectively. The total Kihon Checklist score was significantly weakly to moderately correlated with the CAT score (Spearman’s rank correlation coefficient (Rs)=0.38, p<0.01), the SGRQ total score (Rs=0.65, p<0.01), the Hyland Scale score (Rs=−0.54, p<0.01), all subscale scores of the SF-36 (Rs=−0.64 to −0.31, p<0.01), the BDI score (Rs=−0.46, p<0.01) and the D-12 score (Rs=0.41, p<0.01). We found no or only weak correlations between the total Kihon Checklist score and lung function measurements. We found statistically significant between-group (robust, prefrail and frail) differences in most PRO scores. Using stepwise multiple regression analyses to identify the variables that predicted the total Kihon Checklist score, the SGRQ total score alone significantly explained 49.1% of the variance (p<0.01).

Discussion

Frailty was significantly correlated with PROs, especially health status, unlike lung function. Frailty should be assessed in addition to PROs separately from lung function as part of multidimensional analyses of COPD.
The history of Harborview Medical Center and the Washington State Trauma System
Authors: Bulger Eileen M , Kastl Janet Griffith , Maier Ronald V
Published: July 2017

Harborview Medical Center serves as the sole adult and pediatric level I trauma center for Washington State, and its faculty have led efforts to develop comprehensive systems of trauma care across the country. The Washington State trauma system is an inclusive system that was developed based on data-driven decisions to distribute resources based on population need. This article seeks to explore the history of Harborview Medical Center and the development of the Washington State trauma system to identify the guiding principles and lessons learned, which can facilitate system development for a host of time-sensitive medical conditions.
Successful treatment of acute, severe hypophosphataemia in a dog
Authors: Stewart John A , Main Zoe A , Mellanby Richard J
Published: July 2017

Spontaneous, severe, acute hypophosphataemia is an unusual finding in dogs. This case report describes the presentation of a seven‐year‐old Greyhound with an acute history of polypnoea. Clinical examination revealed an increased rectal temperature, congested mucous membranes, pain on flexion of the right hindlimb and muscle fasciculations. Haematology and plasma biochemistry were generally unremarkable apart from severe hypophosphataemia and a markedly increased creatine kinase concentration. The hypophosphataemia was treated with an intravenous infusion of Toldimphos sodium, which is an organically combined phosphorus preparation. The hypophosphataemic state was rapidly corrected and clinical signs resolved over the following five days. The cause of the severe hypophosphataemia was unclear. This case demonstrates that severe, acute hypophosphataemia can be successfully treated with Toldimphos sodium infusion with a good long‐term outcome even in dogs that are initially presented with debilitating clinical signs.
Compacted soil behaviour through changes of density, suction, and stiffness of soils with remoulding water content
Authors: Zhang T.W. , Cui Y.J. , Lamas-Lopez F. , Calon N. , Costa D’Aguiar S.
Published: July 2017

To better understand the overall hydromechanical behaviour of interlayer soil, the compaction behaviour of one of the two components — the portion of fines (<4 mm) that is sensitive to water content changes — was investigated. The standard Proctor compaction curves were first determined for the soils. Then, the maximum shear modulus, Gmax, and suction were measured on samples statically compacted at an identical dry density, but different remoulding water contents. The changes in Gmaxreveal the existence of a characteristic water content corresponding to the maximum Gmax. The results also show that this characteristic water content increases with the soil plasticity, being similar to the variation trend of optimum water content with soil plasticity. A bimodal pattern was observed from the plot of total suction ψ versus the slope of water content w–log(ψ) curve. The suction corresponding to the maximum Gmaxis close to the lowest point between the two peaks in the ψ–dw/dlog(ψ) curve. A reasonable explanation was attempted for the correspondence between the “optimum water content” defined by the maximum value of Gmaxand the corresponding suction. The difference between the static and dynamic compactions was also explained in terms of suction values.
Chelating effects of carnosine in ameliorating nickel-induced nephrotoxicity in rats
Authors: Hasanein Parisa , Felegari Zhila
Published: July 2017

The kidney is one of the main organs affected by nickel toxicity. We investigated the protective effects of carnosine on nickel-induced oxidative stress in kidney of rats. Animals received NiSO4 (20 mg·kg−1·day−1 intragastrically) and (or) carnosine (10 mg·kg−1·day−1 intragastrically) for 21 days and then were evaluated for biochemical, molecular, and histopathological alterations. Nickel caused an increase in renal levels of malondialdehyde and a decrease in reduced glutathione, catalase, and superoxide dismutase levels and total antioxidant capacity. Carnosine prevented the prooxidant and antioxidant imbalance induced by nickel. Nickel-treated rats showed an increase in serum creatinine, urea, and uric acid with a concomitant decrease in albumin. Nickel markedly accumulated in kidney of exposed rats, but its concentration was effectively reduced by carnosine treatment. Carnosine corrected the biochemical abnormalities and the elevated renal TNF-α and IL-6 levels in the nickel-treated group. It also attenuated nickel-induced abnormalities in renal architecture. Although carnosine showed antioxidant and anti-inflammatory effects in renal tissue of nickel-exposed rats, we cannot clearly attribute the protective effect of carnosine to these effects. Instead, the beneficial effect of carnosine observed in the current study may be due to chelation between nickel and carnosine. Thus, carnosine may represent a therapeutic option to protect against nickel-induced nephrotoxicity that deserves further consideration and examination.
Beneficial effects of rosmarinic acid against alcohol-induced hepatotoxicity in rats
Authors: Hasanein Parisa , Seifi Rosa
Published: July 2017

Alcohol is a severe hepatotoxicant that causes a variety of liver disorders. Rosmarinic acid (RA), a natural phenol, shows some biological activities, including antioxidant and anti-inflammatory effects. We investigated the effects of RA (10 mg/kg) against ethanol-induced oxidative damage and hepatotoxicity in rats. Animals received ethanol (4 g/kg, i.g.) and (or) RA (10 mg/kg, i.g.) daily for 4 weeks. At the end of the treatment period, rats were weighed and use for biochemical, molecular, and histopathological examinations. Ethanol increased hepatic lipid peroxidation (P < 0.001) and decreased hepatic levels of reduced glutathione (P < 0.01), catalase (P < 0.05), and superoxide dismutase (P < 0.001) compared with control group. RA prevented the prooxidant and antioxidant imbalance induced by ethanol in liver. Furthermore, RA ameliorated the increased liver mass, serum levels of ALT, AST, LDH, TNF-α, and IL-6 in ethanol group. Necrosis and infiltration of inflammatory cells in liver parenchyma were attenuated by RA treatment. Our findings showed that RA prevents ethanol-induced oxidant/antioxidant imbalance and liver injury in an experimental model of ethanol-induced hepatotoxicity. Therefore, RA may be a good candidate to protect against ethanol-induced hepatotoxicity; this deserves consideration and further examination.
Olprinone protects the liver from ischemia–reperfusion injury through oxidative stress prevention and protein kinase Akt activation
Authors: Bejaoui Mohamed , Zaouali Mohamed Amine , Sakly Rim , Ben Abdennebi Hassen
Published: July 2017

Liver ischemia–reperfusion (IR) injury is inevitable in surgical procedures such as hepatic resection and liver transplantation. It represents a leading cause of liver graft dysfunction and primary nonfunction after transplantation. Phosphodiesterase (PDE) inhibitors are emerging as effective drugs able to reduce IR damage. The aim of this study was to investigate the effect of selective PDE-3 inhibitor olprinone (Olp) against liver IR injury. Male Wistar rats were subjected to 1 h of partial warm ischemia (70%) followed by 6 h of reperfusion. Before ischemia, rats were treated with saline (IR group), Olp (Olp group), or Olp with Akt inhibitor LY294002 (Olp plus LY group). After reperfusion, hepatic injury (transaminase activities), mitochondrial damage (glutamate dehydrogenase activity), oxidative stress (malondialdehyde and glutathione concentrations and catalase and superoxide dismutase activities), and protein kinase Akt activation were evaluated. Rat treatment with Olp reduced liver injury, prevented mitochondrial damage, decreased lipid peroxidation, and enhanced antioxidant enzymes. Also, Olp induced a significant activation in protein kinase Akt. Inhibition of Akt with LY294002 abolished all of the protective effects of Olp. In conclusion, Olp treatment may be an effective strategy in reducing liver IR injury through oxidative stress prevention and Akt activation.
On the integration of ecological and physiological variables in polar bear toxicology research: a systematic review
Authors: Bechshoft Thea , Derocher Andrew E. , Viengkone Michelle , Routti Heli , Aars Jon , Letcher Robert J. , Dietz Rune , Sonne Christian , Jenssen Bjørn Munro , Richardson Evan , Lunn Nicholas J.
Published: July 2017

Ecotoxicology evolved as a scientific field as awareness of the unintended effects of anthropogenic pollutants in biota increased. Polar bears (Ursus maritimus) are often the focus of Arctic contaminant exposure studies because they are apex predators with high contaminant loads. While early studies focused on describing and quantifying pollutants, present-day polar bear toxicological papers often incorporate ecological variables. This systematic literature review investigates the ecological and physiological variables that have been integrated in such studies. The systematic literature search resulted in 207 papers, published between 1970 and 2016. Representation of each of the 19 polar bear subpopulations varied from 0 to 72 papers; East Greenland, Barents Sea, Southern Beaufort Sea, and Lancaster Sound had the most published research, with over 30 papers each. Samples were collected between 1881 and 2015, primarily from harvested bears (66%); most from the 1990s and 2000s. Adipose tissue, liver, and blood were the most common tissues examined, and mean number of bears analyzed per paper was 76 (range 1–691). Papers investigating temporal trends did so using a mean sample of 61 bears over a 6-year period.The frequency with which ecological and physiological variables were integrated into toxicological papers varied. Age and (or) sex was the only ecological variable(s) considered in 51% of papers. Further, a total of 37% of the papers included in the review investigated physiological effects in relation to contaminant concentrations. Of the papers, 98% dealt with contaminant exposure at the individual level, leaving population level effects largely unstudied. Solitary subadult and adult polar bears were included in 57% and 79% of the papers, respectively. Younger bears were included in fewer papers: yearlings in 20% and cubs-of-the-year in 13%. Only 12% of the papers examined reproduction relative to contaminants. Finally, body condition was included in 26% of the research papers, whereas variables related to polar bear diet were included in ≤9%. Based on our findings, we suggest future polar bear toxicology studies increase sample sizes, include more ecological variables, increase studies on family groups, and increase the applicability of studies to management and conservation by examining pollution effects on reproduction and survival.
Meiosis in interspecific Hordeum hybrids. IV. Tetraploid (4x × 4x) hybrids
Authors: Bothmer Roland von , Flink Jan , Landström Tomas
Published: July 2017

The meiotic pairing behaviour of 31 interspecific combinations of tetraploid Hordeum species are reported. The autoploid H. bulbosum with the II genomic constitution has no homology to the other species. The constitution of tetraploid H. murinum is not clear, but it is not homologous to other tetraploids. Hordeum marinum is a probable autoploid (XX) but with a very strong genetic regulation of pairing. The X genome is possibly found in H. secalinum and H. capense, both of which also possess the H genome in several diploids. Hordeum fuegianum, H. tetraploidum, H. jubatum, H. brachyantherum, and H. roshevitzii are segmental alloploids all with the same two partly homoeologous genomes. Hordeum depressum is probably a segmental alloploid with the H genome and with a very strong pairing regulation. Hordeum brevisubulatum is a pure autoploid with two homologous H genomes.Key words: Hordeum, interspecific hybrids, meiosis, tetraploids.
Inflorescence culture of Triticum aestivum × Secale cereale hybrids: production, characterization and cytogenetic analysis of regenerated plants
Authors: Doré C. , Cauderon Y. , Chueca M. C.
Published: July 2017

In vitro culture of immature inflorescences of F1 hybrid plants originating from the cross between the common wheat cultivar Roazon and two inbred lines of rye was carried out with 2,4-dichlorophenoxyacetic acid in the medium. After 3 or 8 weeks of culture as undifferentiated callus, 62 plants could be regenerated. Of these, 47 reached the adult stage; 46 of which were analysed for chromosome counts and chromosome pairing. For 44 of these, chromosome counts showed high stability and phenotypes were similar to those of the mother plants. In vitro culture of immature inflorescences could therefore be considered as a possible vegetative multiplication method to obtain numerous copies from one individual. The three other plants exhibited variations in phenotype and chromosome number: one was an amphiploid, and a chromosome was lost in each of the other two. All meristematic cells and pollen mother cells were involved in these numerical changes for each plant. The amphiploid plant (2n = 56) was nonchimeric and all the spikes were highly self-fertile. It could be an efficient method for chromosome doubling. This underscores the usefulness of inflorescence tissue culture for overcoming the sterility barrier in interspecific hybrids.Key words: wheat × rye hybrids, tissue culture, amphiploidization, aneuploidy, meiotic behaviour.
A study on genomic relationships of Agropyron trachycaulum with Elymus scabriglumis, E. innovatus, and Hordeum procerum
Authors: Gupta P. K. , Balyan H. S. , Fedak George
Published: July 2017

Synthetic hybrids of Agropyron trachycaulum (2n = 4x = 28) with Elymus scabriglumis (2n = 6x = 42), E. innovatus (2n = 4x = 28), and Hordeum procerum (2n = 6x = 42) were produced through the embryo rescue technique, at relative frequencies of 7.1, 4.2, and 1.8%, respectively, of pollinated florets. The mean chromosome associations in two hybrids with E. scabriglumis was 11.71II + 1.47III + 0.15IV (mean chiasma frequency = 22.75), in one hybrid with H. procerum was 7.27II + 0.63III + 0.09IV (mean chiasma frequency = 10.20) and in a hybrid with E. innovatus was 2.8II (2.19 chiasma frequency). The data suggested two common genomes (S and H) with E. scabriglumis, one common genome (H) with H. procerum, and no common genome with E. innovatus. The evidence obtained suggested a SSHHYY genomic constitution for E. scabriglumis and two genomes different from SH for E. innovatus. The evidence also suggested that in H. procerum there may not be two related genomes present (derived from H. jubatum) as speculated in some earlier studies.Key words: intergeneric hybrids, Agropyron, Elymus, Hordeum, chromosome pairing.
Genetic analysis of growth and maturity in pink salmon (Oncorhynchus gorbuscha)
Authors: Beacham Terry D. , Murray Clyde B.
Published: July 2017

Variation in growth and sexual maturity was examined for five stocks of pink salmon (Oncorhynchus gorbuscha) spawning at different times in British Columbia. In each stock, four males were mated with eight females in a nested breeding design, and the juveniles were reared for 500 d after fry emergence. Adults in early-spawning northern stocks were smaller than those in late-spawning southern ones, but pink salmon from northern stocks had faster growth rates than those from southern ones. The relative ranking within stocks of family weight remained constant after late winter in the year of maturity. Heritability of weight based upon sire variance components was usually greater than 0.9 after 150 d of rearing. Pink salmon from the earlier-spawning stocks were in a more advanced state of sexual maturity when the experiment was terminated than were those from later-spawning stocks, indicative of a significant genetic component in timing of sexual maturity.Key words: Oncorhynchus, salmon, growth rates, sexual maturity.