bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex Differences in Substance Use Among Adult Emergency Department Patients: Prevalence, Severity, and Need for Intervention
Authors: Beaudoin Francesca L. , Baird Janette , Liu Tao , Merchant Roland C.
Published: October 2015

Background

Substance use is prevalent among emergency department (ED) patients, and sex has been implicated as an important factor in the etiology, pathophysiology, sequelae, and treatment of substance use disorders. However, additional information is needed about the epidemiology of substance use as it relates to sex among ED patients.

Objectives

This study examined sex differences in the prevalence and severity of self‐reported tobacco, alcohol, and drug use among adult ED patients.

Methods

A random sample of English‐ or Spanish‐speaking, non–critically ill or injured, 18‐ to 64‐year‐old patients was approached at two urban EDs and asked to self‐report their lifetime and past 3‐month tobacco, alcohol, and drug use. Participants completed the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) using an audio computer‐assisted self‐interview. Participants were categorized by their substance severity (ASSIST score) and need for a brief or more intensive intervention per World Health Organization recommendations. Substance misuse prevalence, frequency, severity, and need for interventions were compared between sexes by substance category. Multivariable logistic regression models were used to examine the association between sexes and the need for intervention after adjusting for sociodemographic characteristics.

Results

Of the 6,432 participants in the study, the median age was 37 years (interquartile range = 26 to 48 years), and 56.6% were female. Overall, lifetime, and past 3‐month use was higher for men across all substances (tobacco, alcohol, and drugs). Among those reporting past 3‐month use, the frequency of use was similar between sexes for tobacco and all drugs, but men reported more frequent alcohol use. Men had higher mean ASSIST scores compared to women, 30.3 (standard error [SE] ± 0.8) vs. 21.1 (SE ± 0.5); mean difference 9.2 (95% confidence interval [CI] = 7.4 to 10.9). The need for any intervention (brief or intensive) was similar between sexes for tobacco and drugs. After sociodemographic factors were adjusted for, women were less likely than men to need any intervention for alcohol (odds ratio [OR] = 0.6; 95% CI = 0.4 to 0.8), but not other substances: tobacco (OR = 0.9; 95% CI = 0.6 to 1.3), marijuana (OR = 0.8; 95% CI = 0.6 to 1.1), or other drugs (OR = 1.1; 95% CI = 0.7 to 1.7).

Conclusions

Although men have a higher overall prevalence of substance use, the frequency and severity of use were similar for men and women for most substances. After other characteristics were adjusted for, sex appears associated with the need for interventions for alcohol, but not tobacco, marijuana, or other drugs.
Comparison of Two Sepsis Recognition Methods in a Pediatric Emergency Department
Authors: Balamuth Fran , Alpern Elizabeth R. , Grundmeier Robert W. , Chilutti Marianne , Weiss Scott L. , Fitzgerald Julie C. , Hayes Katie , Bilker Warren , Lautenbach Ebbing
Published: October 2015

Objectives

The objective was to compare the effectiveness of physician judgment and an electronic algorithmic alert to identify pediatric patients with severe sepsis/septic shock in a pediatric emergency department (ED).

Methods

This was an observational cohort study of patients older than 56 days with fever or hypothermia. All patients were evaluated for potential sepsis in real time by the ED clinical team. An electronic algorithmic alert was retrospectively applied to identify patients with potential sepsis independent of physician judgment. The primary outcome was the proportion of patients correctly identified with severe sepsis/septic shock defined by consensus criteria. Test characteristics were determined and receiver operating characteristic (ROC) curves were compared.

Results

Of 19,524 eligible patient visits, 88 patients developed consensus‐confirmed severe sepsis or septic shock. Physician judgment identified 159 and the algorithmic alert identified 3,301 patients with potential sepsis. Physician judgment had sensitivity of 72.7% (95% confidence interval [CI] = 72.1% to 73.4%) and specificity of 99.5% (95% CI = 99.4% to 99.6%); the algorithmic alert had sensitivity of 92.1% (95% CI = 91.7% to 92.4%) and specificity of 83.4% (95% CI = 82.9% to 83.9%) for severe sepsis/septic shock. There was no significant difference in the area under the ROC curve for physician judgment (0.86, 95% CI = 0.81 to 0.91) or the algorithm (0.88, 95% CI = 0.85 to 0.91; p = 0.54). A combination method using either positive physician judgment or an algorithmic alert improved sensitivity to 96.6% and specificity to 83.3%. A sequential approach, in which positive identification by the algorithmic alert was then confirmed by physician judgment, achieved 68.2% sensitivity and 99.6% specificity. Positive and negative predictive values for physician judgment versus algorithmic alert were 40.3% versus 2.5% and 99.88% versus 99.96%, respectively.

Conclusions

The electronic algorithmic alert was more sensitive but less specific than physician judgment for recognition of pediatric severe sepsis and septic shock. These findings can help to guide institutions in selecting pediatric sepsis recognition methods based on institutional needs and priorities.
Psychiatric patients' perception of physical restraint
Authors: Fugger G. , Gleiss A. , Baldinger P. , Strnad A. , Kasper S. , Frey R.
Published: October 2015

Objective

To investigate psychiatric patients' subjective perception during and after belt fixation.

Method

All patients who were involuntarily admitted and physically restrained at a psychiatric intensive care unit within an 18‐month study period were analysed. Ratings were obtained at four visits when questioning was possible.

Results

Within a heterogeneous diagnostic sample of 47 patients, only 12 patients were eligible to participate during belt fixation. After cessation of fixation, eight patients lacked any memory of restraint, while 36 could be questioned. Visual analogue scale median scores indicated powerlessness and depressiveness rather than anxiety and aggression. Patients' acceptance of the coercive measure was significantly higher (P = 0.003), while patients' memory was significantly lower than expected (P < 0.001). About 50% of the patients documented high perceived coercion, and post‐traumatic stress disorder (PTSD) could be supposed in a quarter of the restrained individuals. Subjective perceptions concerning fixation showed no significant changes over time. Results showed high interindividual variability.

Conclusion

Visual analogue scale revealed that belt fixation seemed to be forgotten or accepted in the majority of patients, probably due to psychiatric intensive care, psychopharmacological treatment and clinical improvements. The responses of a quarter of the patients assessed before discharge may be in accordance with symptoms of PTSD.
Project QUIT (Quit Using Drugs Intervention Trial): a randomized controlled trial of a primary care‐based multi‐component brief intervention to reduce risky drug use
Authors: Gelberg Lillian , Andersen Ronald M. , Afifi Abdelmonem A. , Leake Barbara D. , Arangua Lisa , Vahidi Mani , Singleton Kyle , Yacenda‐Murphy Julia , Shoptaw Steve , Fleming Michael F. , Baumeister Sebastian E.
Published: October 2015

Aims

To assess the effect of a multi‐component primary care delivered brief intervention for reducing risky psychoactive drug use (RDU) among patients identified by screening.

Design

Multicenter single‐blind two‐arm randomized controlled trial of patients enrolled from February 2011 to November 2012 with 3‐month follow‐up. Randomization and allocation to trial group were computer‐generated.

Setting

Primary care waiting rooms of five federally qualified health centers in Los Angeles County (LAC), USA.

Participants

A total of 334 adult primary care patients (171 intervention; 163 control) with RDU scores (4–26) on the World Health Organization (WHO) Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) self‐administered on tablet computers. 261 (78%) completed follow‐up. Mean age was 41.7 years; 62.9% were male; 37.7% were Caucasian.

Intervention(s) and Measurement

Intervention patients received brief (typically 3–4 minutes) clinician advice to quit/reduce their drug use reinforced by a video doctor message, health education booklet and up to two 20–30–minute follow‐up telephone drug use coaching sessions. Controls received usual care and cancer screening information. Primary outcome was patient self‐reported use of highest scoring drug (HSD) at follow‐up.

Findings

Intervention and control patients reported equivalent baseline HSD use at 3‐month follow‐up. After adjustment for covariates, in the complete sample linear regression model, intervention patients used their HSD on 3.5 fewer days in the previous month relative to controls (P<0.001), and in the completed sample model, intervention patients used their HSD 2.2 fewer days than controls (P < 0.005). No compensatory increases in use of other measured substances were found.

Conclusions

A primary‐care based, clinician‐delivered brief intervention with follow‐up coaching calls may decrease risky psychoactive drug use.
Outcomes of high‐volume bariatric surgery in the public system
Authors: Burton Paul , Brown Wendy , Chen Richard , Shaw Kalai , Packiyanathan Andrew , Bringmann Ingra , Smith Andrew , Nottle Peter
Published: October 2015

Background

Bariatric surgery has not been widely used in the Australian public health system. As obesity is strongly associated with socio‐economic status, excluding its use from the public system will deny many of the most in‐need access to a potentially very effective treatment. Alternatively, with rigorous follow‐up and behavioural change requirements, highly successful outcomes in the private system may not translate to the public system.

Methods

The Alfred Hospital rapidly expanded bariatric surgery from 2007. A 6‐year prospective follow‐up study was conducted with annual review of weight, co‐morbidities, retention in follow‐up, serum HbA1c, quality of life and patient satisfaction.

Results

There were 1453 patients. Procedures were predominantly laparoscopic‐adjustable gastric bands (n = 861). Patient details were age 49 ± 11 years, body mass index 50.7 ± 11.2 kg/m2 and weight 139.0 ± 30.2 kg. There was no mortality, and mean length of stay was 1.1 ± 1.2 days. Follow‐up was 98% (1 year) and 85% (6 years). Weight loss was 22 ± 13.1 kg (32.8 ± 18% excess weight loss) at 1 and 30.1 ± 16.8 kg (60 ± 28%) at 6 years. The mean number of co‐morbidities was 4.2 ± 1.1 with significant improvements observed. Patient satisfaction was 7.7 ± 2.3 out of 10. Mental and physical summary scores (SF‐36) improved from 41.02 ± 13.17 to 45.50 ± 13.27 (P < 0.001) and 33.97 ± 10.53 to 44.79 ± 11.19 (P < 0.001).

Conclusions

Patients were older, heavier and suffered more co‐morbid disease than previously reported cohorts. For the first time, excellent outcomes across a range of key quality domains in a large patient cohort have been reported in the public system. High‐volume bariatric surgery in the public system is viable.
Papillary thyroid cancer in childhood: is parental screening helpful?
Authors: Stephenson Carlos , Norlen Olov , Shun Albert , Karpelowsky Jonathon , Robinson Bruce , Delbridge Leigh
Published: October 2015

Background

Familial non‐medullary thyroid cancer (FNMTC) mandates family screening with ultrasound; however, the need for screening paediatric thyroid cancer with no family history has not been addressed.

Methods

This study conducted a retrospective cohort study in a tertiary hospital. The study group is composed of patients ≤18 years undergoing surgery for papillary thyroid cancer (PTC) from 2008 to 2014.

Results

During the study period, 15 paediatric patients had PTC. Only one patient had a prior family history of PTC involving two second‐degree relatives. Of the 30 parents, four were lost to follow‐up, with the remaining 26 undergoing screening thyroid ultrasound. Nodular thyroid disease was documented in eight ultrasounds performed. Subsequently, one has not undergone fine‐needle biopsy, five were benign and two underwent surgical resection: one having a benign follicular adenoma and the other a papillary microcarcinoma with nodal micrometastasis.

Conclusions

Routine ultrasound screening of parents of children presenting with PTC and no family history do not demonstrate an increased incidence of FNMTC. Screening of affected families is likely to demonstrate the expected background incidence of nodular thyroid disease and incidental papillary microcarcinoma. As such, it is unlikely to be useful.
Hepatic venous outflow obstruction in piggyback liver transplantation: single centre experience
Authors: Arudchelvam Joel , Bartlett Adam , McCall John , Johnston Peter , Gane Edward , Munn Stephen
Published: October 2015

Background

Hepatic venous outflow obstruction (HVOO) is a rare but serious complication in liver transplantation (LT).

Methods

We conducted a retrospective analysis of HVOO with venography and gradient measurement in consecutive LT from a single centre.

Results

Five hundred and six LTs were performed in 486 patients with a median age of 49 years (range 3 months to 71 years). Nineteen (3.8%) cases of HVOO were identified. Diagnosis was confirmed at a median of 26 days post‐LT (1–2312). The incidence fell from 5.5% in the first 253 LT, to 2.0% in the second 253 (P = 0.03). Seventeen were due to narrowing at the anastomosis and two cases were due to thrombosis. In adult patients, reconstruction of the supra‐hepatic donor inferior vena cava (IVC) onto two veins versus modified 2–3 hepatic veins did not alter the likelihood of HVOO. 17/19 cases were managed successfully by stenting or venoplasty. Two paediatric patients with early onset HVOO had attempted surgical thrombectomy, one was successful and the other required retransplantation.

Conclusion

The incidence of HVOO appears to fall with increasing experience and does not appear to be related to the number of veins the donor IVC is anastomosed to in adult recipients.
Vaginally obtained amniotic fluid samples in the diagnosis of subclinical chorioamnionitis
Authors: Myntti Tarja , Rahkonen Leena , Tikkanen Minna , Paavonen Jorma , Stefanovic Vedran
Published: October 2015

Introduction

Preterm birth is often caused by infection or inflammation. High concentration of lactate dehydrogenase and low concentration of glucose in amniotic fluid obtained by amniocentesis are associated with subclinical chorioamnionitis. We evaluated amniotic fluid lactate dehydrogenase and glucose concentrations in relation to histologic chorioamnionitis in vaginally obtained samples.

Material and methods

In a prospective study, vaginally obtained amniotic fluid samples were collected from 53 women with preterm prelabor rupture of membranes at 23+4 to 34+5 weeks of gestation at University Hospital, Helsinki, Finland. Amniotic fluid lactate dehydrogenase and amniotic fluid glucose were measured by immunochemiluminometric assays. Histopathologic examination of placenta was performed. The main outcome measure was histologic chorioamnionitis.

Results

Median concentration of vaginally obtained amniotic fluid lactate dehydrogenase was higher in women with histologic chorioamnionitis than in women without (1400 IU/L vs. 784.5 IU/L, p = 0.005). By receiver operating characteristics curve the optimal cut‐off for amniotic fluid lactate dehydrogenase in relation to histologic chorioamnionitis was 1029 IU/L (sensitivity 65%, specificity 69%, positive predictive value 83% and negative predictive value 46%). Amniotic fluid lactate dehydrogenase concentrations showed striking fluctuation in repeat samples. Amniotic fluid glucose concentrations did not differ among women with or without histologic chorioamnionitis (0 mmol/L vs. 0.65 mmol/L, p = 0.20).

Conclusion

Elevated amniotic fluid lactate dehydrogenase was associated with histologic chorioamnionitis, but decreased amniotic fluid glucose was not. However, the clinical value of vaginally obtained amniotic fluid lactate dehydrogenase is limited because of high sample‐to‐sample variability. Better biomarkers for optimal timing of delivery in women with preterm prelabor rupture of membranes are needed.
Mid‐pregnancy fetal biometry, uterine artery Doppler indices and maternal demographic characteristics: role in prediction of small‐for‐gestational‐age birth
Authors: Familiari Alessandra , Bhide Amar , Morlando Maddalena , Scala Carolina , Khalil Asma , Thilaganathan Basky
Published: October 2015

Introduction

The aim of this study was to evaluate the role of mid‐trimester fetal biometry, uterine artery Doppler indices and maternal demographics in prediction of small‐for‐gestational‐age (SGA) birth.

Materials and methods

We conducted a retrospective cohort study in a single referral center. The study included 23 894 singleton pregnancies scanned between 19 and 24 weeks of gestation. Maternal demographics included age, body mass index and ethnicity. Fetal biometry, birthweight and uterine artery pulsatility index values were converted into centiles. Multivariable logistic regression analysis was performed and the predictive accuracy was assessed using receiver operating characteristic curve analysis. The main outcome measure was prediction of delivery of preterm and term SGA neonates defined as a birthweight in the lowest centile groups (<10th, <5th and <3rd centiles).

Results

Maternal ethnicity, fetal biometry and uterine artery Doppler indices were significantly associated with the risk of SGA <5th centile (p < 0.01). Maternal factors or fetal biometry alone showed poor to moderate performance in prediction of term and preterm SGA <5th centile at a 10% false‐positive rate. Uterine artery pulsatility index alone was able to predict 25, 60 and 77% of SGA <5th centile delivering at >37, <37 and <32 weeks of gestation respectively at a 10% false‐positive rate; maternal factors, fetal biometry and uterine artery Doppler combined detected 40, 66 and 89% of term, preterm and very preterm SGA <5th centile at a 10% false‐positive rate.

Conclusions

Second‐trimester screening can identify the majority of pregnancies at high risk of SGA birth and showed a higher performance for earlier gestational ages at birth and lower birthweight centiles.
Neurocontrol of Movement in Humans With Spinal Cord Injury
Authors: Dimitrijevic Milan R. , Danner Simon M. , Mayr Winfried
Published: October 2015

In this review of neurocontrol of movement after spinal cord injury, we discuss neurophysiological evidences of conducting and processing mechanisms of the spinal cord. We illustrate that external afferent inputs to the spinal cord below the level of the lesion can modify, initiate, and maintain execution of movement in absence or partial presence of brain motor control after chronic spinal cord injury. We review significant differences between spinal reflex activity elicited by single and repetitive stimulation. The spinal cord can respond with sensitization, habituation, and dis‐habituation to regular repetitive stimulation. Therefore, repetitive spinal cord reflex activity can contribute to the functional configuration of the spinal network. Moreover, testing spinal reflex activity in individuals with motor complete spinal cord injury provided evidences for subclinical residual brain influence, suggesting the existence of axons traversing the injury site and influencing the activities below the level of lesion. Thus, there are two motor control models of chronic spinal cord injury in humans: “discomplete” and “reduced and altered volitional motor control.” We outline accomplishments in modification and initiation of altered neurocontrol in chronic spinal cord injury people with epidural and functional electrical stimulation. By nonpatterned electrical stimulation of lumbar posterior roots, it is possible to evoke bilateral extension as well as rhythmic motor outputs. Epidural stimulation during treadmill stepping shows increased and/or modified motor activity. Finally, volitional efforts can alter epidurally induced rhythmic activities in incomplete spinal cord injury. Overall, we highlight that upper motor neuron paralysis does not entail complete absence of connectivity between cortex, brain stem, and spinal motor cells, but there can be altered anatomy and corresponding neurophysiological characteristics. With specific input to the spinal cord below the level of the lesion, the clinical status of upper motor neuron paralysis without structural modification can be modified, and movements can be initiated. Thus, external afferent input can partially replace brain control.
Functional Electrical Stimulation in Spinal Cord Injury: Clinical Evidence Versus Daily Practice
Authors: Bersch Ines , Tesini Stefani , Bersch Ulf , Frotzler Angela
Published: October 2015

Functional electrical stimulation (FES) has clinical evidence in the rehabilitation of patients with spinal cord injury as indicated by several studies. Both inpatients and outpatients benefit from the therapeutic effect of the FES. The application areas are multifaceted and can be customized on the need for patients. This is represented by the individuality of the programmability of the stimulators and the variety of stimulation schedules that are based on the knowledge about the effects of FES on structural and functional level. Nevertheless, looking into daily clinical practice, the use of FES is rather poor. Expenditure of time, complexity of technical equipment, and compliance and acceptance of therapists and patients should be taken into account as limiting factors.
Cardiorespiratory and Muscle Metabolic Responses During Conventional Versus Motion Sensor‐Assisted Strategies for Functional Electrical Stimulation Standing After Spinal Cord Injury
Authors: Braz Gustavo P. , Russold Michael F. , Fornusek Ché , Hamzaid Nur Azah , Smith Richard M. , Davis Glen M.
Published: October 2015

This is a case series study with the objective of comparing two motion sensor automated strategies to avert knee buckle during functional electrical stimulation (FES)—standing against a conventional hand‐controlled (HC) FES approach. The research was conducted in a clinical exercise laboratory gymnasium at the University of Sydney, Australia. The automated strategies, Aut‐A and Aut‐B, applied fixed and variable changes of neurostimulation, respectively, in quadriceps amplitude to precisely control knee extension during standing. HC was an “on‐demand” increase of stimulation amplitude to maintain stance. Finally, maximal FES amplitude (MA) was used as a control condition, whereby knee buckle was prevented by maximal isometric muscle recruitment. Four AIS‐A paraplegics undertook 4 days of testing each, and each assessment day comprised three FES standing trials using the same strategy. Cardiorespiratory responses were recorded, and quadriceps muscle oxygenation was quantified using near‐infrared spectroscopy. For all subjects, the longest standing times were observed during Aut‐A, followed by Aut‐B, and then HC and MA. The standing times of the automated strategies were superior to HC by 9–64%. Apart from a lower heart rates during standing (P = 0.034), the automation of knee extension did not promote different cardiorespiratory responses compared with HC. The standing times during MA were significantly shorter than during the automated or “on‐demand” strategies (by 80–250%). In fact, the higher isometric‐evoked quadriceps contraction during MA resulted in a greater oxygen demand (P < 0.0001) and wider arteriovenous oxygen extraction (P = 0.08) when compared with the other strategies. In conclusion, even though increased standing times were demonstrated using automated control of knee extension, physiological benefits compared with HC were not evident.
Comparison of Twitch Responses During Current‐ or Voltage‐Controlled Transcutaneous Neuromuscular Electrical Stimulation
Authors: Vargas Luna José Luis , Krenn Matthias , Löfler Stefan , Kern Helmut , Cortés R. Jorge A. , Mayr Winfried
Published: October 2015

Neuromuscular electrical stimulation (NMES) is an established method for functional restoration of muscle function, rehabilitation, and diagnostics. In this work, NMES was applied with surface electrodes placed on the anterior thigh to identify the main differences between current‐controlled (CC) and voltage‐controlled (VC) modes. Measurements of the evoked knee extension force and the myoelectric signal of quadriceps and hamstrings were taken during stimulation with different amplitudes, pulse widths, and stimulation techniques. The stimulation pulses were rectangular and symmetric biphasic for both stimulation modes. The electrode‐tissue impedance influences the differences between CC and VC stimulation. The main difference is that for CC stimulation, variation of pulse width and amplitude influences the amount of nerve depolarization, whereas VC stimulation is only dependent on amplitude variations for pulse widths longer than 150 μs. An important remark is that these findings are strongly dependent on the characteristics of the electrode‐skin interface. In our case, we used large stimulation electrodes placed on the anterior thigh, which cause higher capacitive effects. The controllability, voltage compliance, and charge characteristics of each stimulation technique should be considered during the stimulators design. For applications that require the activation of a large amount of nerve fibers, VC is a more suitable option. In contrast, if the application requires a high controllability, then CC should be chosen prior to VC.
Effects of Functional Electrical Stimulation on Denervated Laryngeal Muscle in a Large Animal Model
Authors: Cheetham Jon , Perkins Justin D. , Jarvis Jonathan C. , Cercone Marta , Maw Martin , Hermanson John W. , Mitchell Lisa M. , Piercy Richard J. , Ducharme Norm G.
Published: October 2015

Bilateral vocal fold paralysis (BVCP) is a life‐threatening condition that follows injury to the Recurrent Laryngeal nerve (RLn) and denervation of the intrinsic laryngeal musculature. Functional electrical stimulation (FES) enables restoration and control of a wide variety of motor functions impaired by lower motor neuron lesions. Here we evaluate the effects of FES on the sole arytenoid abductor, the posterior cricoarytenoid (PCA) muscle in a large animal model of RLn injury. Ten horses were instrumented with two quadripolar intramuscular electrodes in the left PCA muscle. Following a 12‐week denervation period, the PCA was stimulated using a once‐daily training session for 8 weeks in seven animals. Three animals were used as unstimulated controls. Denervation produced a significant increase in rheobase (P < 0.001). Electrical stimulation produced a 30% increase in fiber diameter in comparison with the unstimulated control group (33.9 ± 2.6 µm FES+, 23.6 ± 4.2 µm FES−, P = 0.04). A trend toward a decrease in the proportion of type 1 (slow) fibers and an increase in type 2a (fast) fibers was also observed. Despite these changes, improvement in PCA function at rest was not observed. These data suggest that electrical stimulation using a relatively conservative set of stimulation parameters can reverse the muscle fiber atrophy produced by complete denervation while avoiding a shift to a slow (type 1) fiber type.
Nitric oxide and Na,K‐ATPase activity in rat skeletal muscle
Authors: Juel C.
Published: October 2015

Aim

It has been suggested that nitric oxide (NO) stimulates the Na,K‐ATPase in cardiac myocytes. Therefore, the aims of this study were to investigate whether NO increases Na,K‐ATPase activity in skeletal muscle and, if that is the case, to identify the underlying mechanism.

Method

The study used isolated rat muscle, muscle homogenates and purified membranes as model systems. Na,K‐ATPase activity was quantified from phosphate release due to ATP hydrolysis.

Results

Exposure to the NO donor spermine NONOate (10 μm) increased the maximal Na,K‐ATPase activity by 27% in isolated glycolytic muscles, but had no effect in oxidative muscles. Spermine NONOate increased the maximal Na,K‐ATPase activity by 58% (P < 0.05) in homogenates from glycolytic muscle, but had no effect in oxidative muscle. The stimulatory effect of NONOate was not related to one specific Na,K‐ATPase α‐isoform. Incubation with cGMP (1 mm) increased the maximal Na,K‐ATPase activity in homogenates from glycolytic muscle by 16% (P < 0.05), but had no effect on homogenates from oxidative muscle. cGMP had no effect on phospholemman phosphorylation at serine 68. Spermine NONOate had no effect in muscle membranes in which the ATPase activity was depressed by oxidized glutathione.

Conclusion

NO and cGMP stimulate the Na,K‐ATPase in glycolytic skeletal muscle. Direct S‐nitrosylation and interference with S‐glutathionylation seem to be excluded. In addition, phosphorylation of phospholemman at serine 68 is not involved. Most likely, the NO/cGMP/protein kinase G signalling pathway is involved.
Systematic review with meta‐analysis: self‐expanding metal stents in patients with cirrhosis and severe or refractory oesophageal variceal bleeding
Authors: Marot A. , Trépo E. , Doerig C. , Moreno C. , Moradpour D. , Deltenre P.
Published: October 2015

Background

The prognosis of patients with cirrhosis and acute variceal bleeding is very poor when the standard‐of‐care fails to control bleeding. New treatment modalities are needed in these patients.

Aim

To synthesise the available evidence on the efficacy of self‐expanding metal stents (SEMS) in patients with cirrhosis and severe or refractory oesophageal variceal bleeding.

Methods

Meta‐analysis of trials evaluating SEMS in patients with cirrhosis and severe or refractory oesophageal variceal bleeding.

Results

Thirteen studies were included. The pooled estimate rates were 0.40 (95% confidence interval, CI = 0.31–0.49) for death, 0.41 (95% CI = 0.29–0.53) for liver‐related death and 0.36 (95% CI = 0.26–0.47) for death at day 30, with low heterogeneity between studies. The pooled estimate rates were 0.12 (95% CI = 0.07–0.21) for mortality related to variceal bleeding, and 0.18 (95% CI = 0.11–0.29) for failure to control bleeding with SEMS, with no or low heterogeneity between studies. The pooled estimate rate were 0.16 (95% CI = 0.04–0.48) for rebleeding after stent removal and 0.28 (95% CI = 0.17–0.43) for stent migration, with high heterogeneity. A significant proportion of patients had access to liver transplantation or to TIPSS [pooled estimate rate 0.10 (95% CI = 0.04–0.21) and 0.26 (95% CI = 0.18–0.36), respectively].

Conclusions

Fewer than 40% of patients treated with SEMS were dead at 1 month. SEMS can be used as a bridge to TIPSS or to liver transplantation in a significant proportion of patients. Additional studies are required to identify potential risk factors leading to a poor prognosis in patients with acute variceal bleeding in whom the use of SEMS could be considered.
Comparison of active dry yeast (Saccharomyces cerevisiae) and yeast culture for growth performance, carcass traits, meat quality and blood indexes in finishing bulls
Authors: Geng Chun‐Yin , Ren Li‐Ping , Zhou Zhen‐Ming , Chang Ying , Meng Qing‐Xiang
Published: October 2015

This study was conducted to compare the effect of active dry yeasts (ADY) and yeast cultures (YC), two typical products of yeast preparations, on growth performance, carcass characteristics, meat quality and blood indexes in finishing bulls fed a high‐concentrate diet. Forty‐five finishing bulls (mean body weight (BW) ± standard deviation: 505 ± 29 kg BW) were allocated to three groups of 15 bulls and assigned randomly to one of three diets which were CON diet (basal diet), ADY diet (basal diet + Levucell SC) and YC diet (basal diet + Diamond V XP), respectively. After 98 days of trial, all bulls were slaughtered. The result showed that ADY rather than YC improved growth performance and carcass traits of bulls compared to CON. Moreover, both ADY and YC improved beef tenderness and changed blood indexes related to fat metabolism. In conclusion, ADY had more pronounced effect on growth performance of bulls fed high‐concentrate diet, and both ADY and YC improved the beef quality by intensive fat metabolism.
Journey fromNGOto Sustainable Social Enterprise: Acceleratory Organizational Factors ofBRAC
Authors: Cho Sangmi , Sultana Razia
Published: October 2015

The purpose of this study is to explore the organizational factors that accelerate for turning BRAC into a sustainable Social Enterprise (SE). As such, using the organization BRAC as a case study, this study focused on two main objectives: first, to explore its organizational strategy or approach as SE and second, to evaluate the ability of the organization to maintain its organizational value as an NGO while operating SEs. This work constitutes exploratory research based on case study method. The data collection method is divided into two parts: in the first part the relevant literature was reviewed, and in the second part purposive sampling method was used in the form of an in‐depth interview. Findings suggests that BRAC generated some key organizational factors including addressing specific social and client's needs, introduced unique ‘BRAC Model’ and strategy for their SEs, visionary leadership and competent management with proper organizational foundation assist the organization in its capacity to become a sustainable and successful SE. This research has policy implications findings common elements yet innovative approaches for establishing SE among NGOs in Bangladesh, in order to come up with institutional regulations in informal economy and instable political system.
Darier disease in Israel: combined evaluation of genetic and neuropsychiatric aspects
Authors: Dodiuk-Gad R.P. , Cohen-Barak E. , Khayat M. , Milo H. , Amariglio-Diskin L. , Danial-Faran N. , Sah M. , Ziv M. , Shani-Adir A. , Amichai B. , Zlotogorski A. , Borochowitz Z. , Rozenman D. , Shalev S.
Published: October 2015

Background

Darier disease (DD) is a rare genodermatosis caused by heterozygous mutations in the ATP2A2 gene. It has been associated with neuropsychiatric manifestations.

Objectives

To investigate the genetic basis of Israeli patients with DD, and its association with the neuropsychiatric phenotype.

Methods

A cohort of 32 families comprising 74 affected individuals and 13 unaffected family members was recruited from the Haemek Dermatology Department and other dermatology clinics in Israel. The individuals were evaluated by detailed questionnaires, physical examination and genetic analysis. The main outcome measures were genetic mutations, psychiatric profile and their association.

Results

Twenty-three mutations in ATP2A2 were scattered over the entire gene, 14 of them novel. Two families shared the same mutation. Twenty-one patients (28%) had a history of psychiatric disorders, most of them mood disorders. Another seven patients (9%) were highly suspected of having a psychiatric disorder; 21 (28%) reported suicidal thoughts and five (7%) had attempted suicide. The psychiatric phenotype demonstrated inter- and intrafamilial variability, and was not associated with disease severity, family history of psychiatric disease or mutation location.

Conclusions

The cohort demonstrated genetic heterogeneity with no mutation cluster along the gene, and a high prevalence of psychiatric disorders. Although no clear genotype–phenotype correlation was found, the results point to a major effect of genetic background on psychiatric phenotype, together with other modifiers.
Efficacy and safety of follow-up field treatment of actinic keratosis with ingenol mebutate 0·015% gel: a randomized, controlled 12-month study
Authors: Garbe C. , Basset-Seguin N. , Poulin Y. , Larsson T. , Østerdal M.L. , Venkata R. , Lear J.T.
Published: October 2015

Background

Ingenol mebutate (IngMeb) is a novel patient-applied topical field therapy for actinic keratosis.

Objectives

To demonstrate the efficacy and safety of follow-up IngMeb field treatment of actinic keratoses (AKs) present at 8 weeks after initial treatment or emerging in a previously cleared field.

Methods

In this phase III, randomized, double-blind study in patients with 4–8 clinically visible AKs within a contiguous 25-cm2 treatment area on the face or scalp, all patients were treated initially with IngMeb 0·015% gel for three consecutive days. If lesions were present in the field at 8 weeks, or emerged at weeks 26 or 44, patients were randomized (2 : 1) to follow-up IngMeb or vehicle gel for three consecutive days. The main outcome was complete clearance rates of AKs 8 weeks after randomization.

Results

Of 450 patients who received initial treatment with IngMeb, 61·6% demonstrated complete clearance at 8 weeks. Patients with AKs present at 8 weeks or emerging at weeks 26 or 44 were randomized to IngMeb (n = 134) or vehicle (n = 69). IngMeb achieved a higher complete clearance rate than vehicle 8 weeks after randomization in AKs present at 8 weeks (46·7% vs. 18·4%; P < 0·01) and in emergent AKs (59·5% vs. 25·0%; P = 0·01). Based on those who completed 12 months of follow-up (n = 340), the overall 12-month clearance rate was estimated at 50·0%. Follow-up IngMeb treatment was well tolerated.

Conclusions

This study demonstrated the long-term benefit of IngMeb 0·015% gel for initial and follow-up therapy of AKs.
Nicastrin mutations in familial acne inversa impact keratinocyte proliferation and differentiation through the Notch and phosphoinositide 3-kinase/AKT signalling pathways
Authors: Xiao X. , He Y. , Li C. , Zhang X. , Xu H. , Wang B.
Published: October 2015

Background

Acne inversa (AI) is a chronic inflammatory skin disease with an autosomal dominant inheritance pattern. Mutations of the gene encoding nicastrin (NCSTN), a cofactor subunit of γ-secretase, are responsible for familial AI. However, whether deficiency of nicastrin is functionally implicated in the biological behaviours of human keratinocytes and related molecular mechanisms remains unknown.

Objectives

To study alterations of biological traits and related signalling pathways modulated by nicastrin knockdown in keratinocytes.

Methods

A human immortalized keratinocyte cell line (HaCaT) was treated with efficient small interfering (si)RNA-targeted NCSTN. Cell proliferation was measured by CCK-8 assay; cell-cycle and cell apoptosis analyses were detected by flow cytometry. Microarray analysis was applied to uncover impacts of NCSTN silencing on whole-genome expression of HaCaT cells. Altered signalling pathways were further confirmed by real-time polymerase chain reaction, Western blotting and immunohistochemistry in both HaCaT cells and lesions of a patient with AI with NCSTN mutation.

Results

NCSTN knockdown in HaCaT cells impaired γ-secretase activity, leading to increased cell proliferation and S-phase population. Microarray data also showed that numerous genes and pathways implicated in proliferation and differentiation of keratinocytes were statistically changed. Among these genes, expression levels of several Notch pathway molecules, known as γ-secretase substrates, were validated to be significantly attenuated in both nicastrin-silencing HaCaT cells and the lesion of the patient. Furthermore, a remarkable elevation of expression of phosphoinositide 3-kinase (PI3K), AKT and its activated form pAKT was illustrated in siRNA-treated HaCaT cells.

Conclusions

Deficiency of the NCSTN in familial AI may regulate proliferation and differentiation of keratinocytes mainly through the Notch and PI3K/AKT signalling pathways.
Continuous positive airway pressure-associated cutaneous amoebiasis in an immunosuppressed patient
Authors: Sells R.E. , Chen C.A. , Wong M.T. , Zimarowski M.J. , Kirby J.E. , Joyce R.M. , Wu P.A.
Published: October 2015

Organisms of the genus Acanthamoeba are environmentally ubiquitous and colonizers of the oral mucosa in humans. While largely asymptomatic in healthy persons, Acanthamoeba infection can cause disseminated disease with poor prognosis in immunosuppressed populations. Here we report a unique case of cutaneous amoebiasis associated with continuous positive airway pressure use in an immunosuppressed patient.
Propranolol in the treatment of infantile haemangiomas: lessons from the European Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce survey
Authors: Wedgeworth E. , Glover M. , Irvine A.D. , Neri I. , Baselga E. , Clayton T.H. , Beattie P.E. , Bjerre J.V. , Burrows N.P. , Foelster-Holst R. , Hedelund L. , Hernandez-Martin A. , Audrain H. , Bhate K. , Brown S.J. , Baryschpolec S. , Darne S. , Durack A. , Dvorakova V. , Gach J. , Goldstraw N. , Goodyear H. , Grabczynska S. , Greenblatt D. , Halpern J. , Hearn R.M.R. , Hoey S. , Hughes B. , Jayaraj R. , Johansson E.K. , Lam M. , Leech S. , O'Regan G.M. , Morrison D. , Porter W. , Ramesh R. , Schill T. , Shaw L. , Taylor A.E.M. , Taylor R. , Thomson J. , Tiffin P. , Tsakok M. , Janmohamed S.R. , Laguda B. , McPherson T. , Oranje A.P. , Patrizi A. , Ravenscroft J.C. , Shahidullah H. , Solman L. , Svensson A. , Wahlgren C.F. , Hoeger P.H. , Flohr C.
Published: October 2015

Background

Oral propranolol is widely prescribed as first-line treatment for infantile haemangiomas (IHs). Anecdotally, prescribing practice differs widely between centres.

Objectives

The Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce was founded to establish patterns of use of propranolol in IHs.

Methods

Participating centres entered data on all of their patients who had completed treatment with oral propranolol for IHs, using an online data capture tool.

Results

The study cohort comprised 1097 children from 39 centres in eight European countries. 76·1% were female and 92·8% had a focal IH, with the remainder showing a segmental, multifocal or indeterminate pattern. The main indications for treatment were periocular location (29·3%), risk of cosmetic disfigurement (21·1%) and ulceration and bleeding (20·6%). In total 69·2% of patients were titrated up to a maintenance regimen, which consisted of 2 mg kg−1 per day (85·8%) in the majority of cases. 91·4% of patients had an excellent or good response to treatment. Rebound growth occurred in 14·1% upon stopping, of whom 53·9% were restarted and treatment response was recaptured in 91·6% of cases. While there was no significant difference in the treatment response, comparing a daily maintenance dose of < 2 mg kg−1 vs. 2 mg kg−1 vs. > 2 mg kg−1, the risk of adverse events was significantly higher: odds ratio (OR) 1 vs. adjusted OR 0·70, 95% confidence interval (CI) 0·33–1·50, P = 0·36 vs. OR 2·38, 95% CI 1·04–5·46, P = 0·04, Ptrend < 0·001.

Conclusions

The PITCH survey summarizes the use of oral propranolol across 39 European centres, in a variety of IH phases, and could be used to inform treatment guidelines and the design of an interventional study.
Testing commonly used X‐ray fluorescence core scanning‐based proxies for organic‐rich lake sediments and peat
Authors: Chawchai Sakonvan , Kylander Malin E. , Chabangborn Akkaneewut , Löwemark Ludvig , Wohlfarth Barbara
Published: October 2015

X‐ray fluorescence (XRF) core scanning has become widely available for geological studies during the last decade. The data obtained from XRF core scanning, however, may be strongly influenced by the amount of organic matter, water content, density and porosity of the sediment matrix. In this study we discuss the usefulness of XRF core scanning to distinguish different kinds of organic‐rich sediments and peat based on examples from tropical Lakes Kumphawapi and Nong Leng Sai in Thailand. We examined how sedimentary factors influence XRF core scanning analyses by comparing elemental and scattering ratios to lithological changes and quantitative LOI, TOC, biogenic silica (BSi) and grain‐size values. Our comparison suggests that the (inc/coh) scattering ratio is of limited use as an indicator for variations in LOI and TOC in peaty gyttja or peat. In Lake Kumphawapi's sediments, Si/Ti ratios reflect clastic input associated with grain‐size variations rather than BSi contents. The Ti‐normalized ratios of Si, Zr, Sr, K and Rb are linked to mineral input and associated grain‐size variations. We conclude that XRF core scanning of organic‐rich tropical lake sediments and peat is useful to infer palaeoenvironmental conditions. However, XRF core scanning data does not stand‐alone and needs to be underpinned by additional proxies.
MicroRNA‐27b suppresses tumor progression by regulating ARFGEF1 and focal adhesion signaling
Authors: Matsuyama Rei , Okuzaki Daisuke , Okada Masato , Oneyama Chitose
Published: October 2015

The non‐receptor tyrosine kinase c‐Src is frequently activated during progression of colon cancers. In this study, we found that among the c‐Src‐regulated microRNAs (miRNAs), miR‐27b is also repressed by activation of K‐Ras/H‐Ras. Inhibitor studies suggested that the phosphatidylinositol 3‐kinase pathway is involved in the repression of miR‐27b. MicroRNA‐27b was repressed in various colon cancer cell lines and tumor tissues. Re‐expression of miR‐27b in human colon cancer HCT116 cells caused morphological changes and suppressed tumor growth, cell adhesion, and invasion. We also identified ARFGEF1 and paxillin as novel targets of miR‐27b, and found that miR‐27b‐mediated regulation of ARFGEF1 is crucial for controlling anchorage‐independent growth, and that of paxillin is important for controlling cell adhesion and invasion. Re‐expression of miR‐27b suppressed the activation of c‐Src induced by integrin‐mediated cell adhesion, suggesting that repression of miR‐27b may contribute to c‐Src activation in cancer cells. These findings show that miR‐27b functions as a tumor suppressor by controlling ARFGEF1 and the paxillin/c‐Src circuit at focal adhesions.
Confirmatory factor analysis of the Strengths and Difficulties Questionnaire in Singaporean kindergartners
Authors: Bull R. , Lee K. , Koh I. H. C , Poon K. K. L
Published: October 2015

Background

The Strengths and Difficulties Questionnaire (SDQ) assesses behavioural adjustment in children aged 3 to 16 years. To ascertain the appropriateness of the scale for a specific population, it is important to examine whether the distinctiveness of the scale dimensions can be verified empirically.

Aims

Confirmatory factor analysis was used to test explicitly which of three models better explain our data, and whether model fit was improved by the addition of method factors.

Methods

Parents of 411 Singaporean kindergartners completed the SDQ.

Results

A four‐factor multi‐trait multi‐method model (Prosocial, Conduct, Hyperactivity, Internalizing and two method factors) provided the best fit to the data. There was strong evidence for convergent and discriminant validity. However, differences in configural loading pattern indicated gender‐related differences in the mapping of the SDQ items.

Discussion

Differences in factor structure across countries and gender may reflect differing conceptions of the underlying dimensions, as well as differences in normative expectations. However, our findings may allow its use as a screening tool to identify Singaporean children at risk of emotional and behavioural difficulties.