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Παρασκευή 13 Ιουλίου 2018

Improved iterative shrinkage-thresholding for sparse signal recovery via Laplace mixtures models

In this paper, we propose a new method for support detection and estimation of sparse and approximately sparse signals from compressed measurements. Using a double Laplace mixture model as the parametric repre...

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Sequential convex combinations of multiple adaptive lattice filters in cognitive radio channel identification

Sequential convex combinations of multiple adaptive lattice filters using different exponential weighting factors in cognitive radio (CR) channel identification framework have been considered in this presentat...

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The Effect of Problematic Internet Use, Social Appearance Anxiety, and Social Media Use on Nursing Students' Nomophobia Levels

This study examined the effect of problematic Internet use, social appearance anxiety, and social media use on nursing students' nomophobia levels. This study was conducted with 755 undergraduate nursing students. Sociodemographic data were evaluated using percentages and means. The effect of problematic Internet use, social appearance anxiety, and social media use on nomophobia levels was assessed by simple linear regression analysis. The mean age of participants was 21.4 ± 1.3; 82.5% were female, and 59.7% (n = 450) had adequate incomes. According to the regression analysis, nomophobia levels have a strong, positive, and significant relationship with the variables of problematic Internet use (β = .39, P

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Spontaneous Changes in Functional Connectivity of Independent Components of fMRI Signal in Healthy Volunteers at Rest and in Subjects with Mild Depression

Depression is associated with changes in the pattern of interaction of cerebral networks, which can reflect both existing symptoms and compensatory processes. The study is based on analysis of resting state fMRI data from 15 patients with mild depression and 19 conventionally healthy individuals. From fMRI signal recorded at rest for 4 min, the independent components were reconstructed. The intergroup differences and dynamics of functional connectivity from the first to the second recording were analyzed. Initially, depressive patients demonstrated weaker connectivity between cerebellar declive network (CN) and left central executive network (CEN) and also sensorimotor network (SMN); left CEN and primary visual network (PVN). During the second recording, the patients demonstrated more intensive reciprocal connection of the dorsal domain of default mode network (DMN) and auditory network (AN). In healthy subjects, positive correlations of the dorsal DMN and left CEN, right CEN and CN, and negative correlation of dorsal DMN and visuospatial network weakened from the first to second record. In the depression group, the interaction of AN with PVN, the right CEN with the anterior salience network and with ventral DMN weakened. At the same time, the connectivity between SMN and CN were strengthened. The results can be interpreted as spontaneous normalization of brain activity, but no direct evidence for their relation to the improvement of depression symptoms was found.



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Specific Features of Transcription Activity of Cancer-Testis Antigens in Patients with Metastatic and Non-Metastatic Breast Cancer

Cancer-testis antigens, effective markers of tissue malignant transformation, are characterized by heterogonous transcription depending on the pathological features of breast cancer. We performed screening of transcription profile of cancer-testis antigens specific for breast tumor tissues in female patients with and without regional metastasis. The relative expression of 16 genes (MAGEA1, MAGEA2, MAGEA3, MAGEA4, MAGEB1, MAGEB2, GAGE1, GAGE3, GAGE4, MAGEC1, BAGE, XAGE3, NY-ESO1, SSX2, SYCP1, and PRAME1) was analyzed by RT-qPCR method in biopsy specimens of the mammary gland tissues obtained during surgery from 25 patients. Differential transcription activity of cancer-testis antigens genes was observed in patients with metastatic (enhanced expression of MAGEA2, MAGEB1, and XAGE3 genes) and non-metastatic (enhanced expression of GAGE3 and PRAME1 genes) breast cancer.



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Mismatch repair deficiency assessment by immunohistochemistry: for Lynch syndrome screening and beyond

Future Oncology, Ahead of Print.


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Associations between sleep quality and its domains and insufficient physical activity in a large sample of Croatian young adults: a cross-sectional study

Objectives

The main purpose of the present study was to explore the associations between sleep quality and insufficient physical activity.

Design

Cross-sectional.

Setting

Faculties in Croatia.

Participants

2100 university students (1049 men and 1051 women) aged 18–24 years were recruited.

Primary outcome

To assess the domains of sleep quality (independent variables) and 'insufficient' physical activity (dependent variable), we used previously validated Pittsburgh Sleep Quality Index and International Physical Activity questionnaires. Logistic regressions were used to calculate the associations between the sleep quality and 'insufficient' physical activity.

Results

When sleep quality domains were entered separately into the model, very bad subjective sleep quality (OR 3.09; 95% CI 1.50 to 6.56), >60 min of sleep latency (OR 2.17; 95% CI 1.39 to 3.39), <7 hours of sleep (OR 1.56; 95% CI 1.24 to 1.96), <65% of habitual sleep efficiency (OR 2.26; 95% CI 1.26 to 4.05), sleep disturbances >1/week (OR 1.61; 95% CI 1.03 to 2.52), use of sleep medication >1/week (OR 3.35; 95% CI 1.83 to 6.10), very big daytime dysfunction problem (OR 2.78; 95% CI 1.57 to 4.93) and poor sleep quality (1.53; 95% CI 1.23 to 1.91) were associated with 'insufficient' physical activity. When all sleep quality domains were entered simultaneously into the model, the same significant associations remained, except for sleep disturbances. Both models were adjusted for gender, body mass index, self-rated health, life satisfaction, socioeconomic status, presence or absence of chronic diseases, smoking status, binge drinking and psychological distress.

Conclusions

Our results show that 'poor' sleep quality is associated with 'insufficient' physical activity in young adults. In order to improve, special strategies and policies that leverage 'good sleep' quality are warranted.



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Evaluating the impact of a community health worker programme on non-communicable disease, malnutrition, tuberculosis, family planning and antenatal care in Neno, Malawi: protocol for a stepped-wedge, cluster randomised controlled trial

Introduction

This protocol concerns the implementation and evaluation of an intervention designed to realign the existing cadre of community health workers (CHWs) in Neno district, Malawi to better support the care needs of the clients they serve. The proposed intervention is a 'Household Model' where CHWs will be reassigned to households, rather than to specific patients with HIV and/or tuberculosis (TB).

Methods and analysis

Using a stepped-wedge, cluster-randomised design, this study investigates whether high HIV retention rates can be replicated for non-communicable diseases (NCDs), and the model's impact on TB and paediatric malnutrition case finding, as well as the uptake of family planning and antenatal care. Eleven sites (health centres and hospitals) were arranged into six clusters (average cluster population 21 800). Primary outcomes include retention in care for HIV and chronic NCDs, TB case finding, paediatric malnutrition case finding, and utilisation of early and complete antenatal care. Clinical outcomes are based on routinely collected data from the Ministry of Health's District Health Information System 2 and an OpenMRS electronic medical record supported by Partners In Health. Additionally, semistructured qualitative interviews with various stakeholders will assess community perceptions and context of the Household Model.

Ethics and dissemination

Ethics approval has been obtained from the Malawian National Health Science Research Committee (#16/11/1694) in Lilongwe, Malawi; Partners Healthcare Human Research Committee (#2017P000548/PHS) in Somerville, Massachusetts; and the Biomedical and Scientific Research Ethics Sub-Committee (REGO-2017–2060) at the University of Warwick in Coventry, UK. Dissemination will include manuscripts for peer-reviewed publication as well as a full report detailing the findings of the intervention for the Malawian Ministry of Health.

Trial registration number

NCT03106727.

Primary sponsor

Partners In Health | Abwenzi Pa Za Umoyo P.O. Box 56, Neno, Malawi. Protocol Version 4, March 2018.



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Different predictors of pain severity across age and gender of a Chinese rural population: a cross-sectional survey

Objectives

To investigate a 4-week period of pain prevalence and the risk factors of experiencing pain among a rural Chinese population sample. To explore the psychosocial and health condition predictors of pain severity and the interactions of age and gender with these factors in real-life situations among the general adult population in China.

Methods

Data were collected from a random multistage sample of 2052 participants (response rate=95%) in the rural areas of Liuyang, China. Visual analogue scale was used to assess participants' pain experienced and a series of internationally validated instruments to assess their sociodemographic characteristics, self-reported health status, depression symptoms, anxiety symptoms, sleep quality, self-efficacy and perceived stress.

Results

The pain prevalence over the 4-week period in rural China was 66.18% (62.84% for men and 68.82% for women). A logistic regression model revealed that being female (adjusted OR=1.58, 95% CI 1.24 to 2.02), age (adjusted OR=1.03, 95% CI 1.02 to 1.05), depressive symptoms (adjusted OR=1.07, 95% CI 1.02 to 1.13) and medium-quality sleep (adjusted OR=2.14, 95% CI 1.26 to 3.64) were significant risk factors for experiencing pain. General linear model analyses revealed that (1) pain severity of rural Chinese was related to self-rated physical health and social health; (2) the interactions of age, gender with employment status, depression symptoms, perceived stress and physical health were significant. Simple effect testing revealed that in different age groups, gender interacted with employment status, depression symptoms, perceived stress and physical health differently.

Conclusions

Improving physical and social health could be effective in reducing the severity of pain and the treatment of pain should be designed specifically for different ages and genders among the general population.



https://ift.tt/2umQnS5

Importance of clinical educators to research use and suggestions for better efficiency and effectiveness: results of a cross-sectional survey of care aides in Canadian long-term care facilities

Objective

This study explored the effect of clinical educators as facilitators of research use and how it may be modified by organisational context in the settings.

Design

Cross-sectional observational study.

Setting

A representative sample of 91 residential long-term care (LTC) facilities across Western Canada.

Participants

We used surveys to collect data from the frontline care aides and information about the organisational context of the care units.

Outcome measure and explanatory variables

We assessed research use (the outcome) with the Conceptual Research Utilization (CRU) scale. Explanatory variables in the multiple regression analysis were facilitation, organisational context and the interaction terms. Facilitation was measured by the frequency of contacts between care aides and clinical educator or person who brings new ideas about resident care. Three core organisational context variables were measured using the Alberta Context Tool.

Results

We included data of 3873 care aides from 294 care units in the LTC facilities. We found significant associations between CRU and facilitation, leadership, culture and evaluation. Interactions of facilitation x leadership and facilitation x culture were negative. The coefficient of the facilitation x evaluation term in the regression model was positive (0.019, 95% CI 0.012 to 0.026), suggesting synergistic effects between facilitation and a well-developed process to evaluate care quality using relevant data.

Conclusions

Findings indicate clinical educators are effective facilitators of research use among the care aides, but the effect is modified by organisational context. For greatest impact, managers can direct efforts of the clinical educators to care units where leadership and culture ratings are lowest, but a proficient feedback and evaluation process is in place. This understanding enables managers to deploy clinical educators (a scarce resource in LTC settings) most efficiently.



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Patient-rated importance of key information on screening colonoscopy in Germany: a survey of statutory health insurance members

Background

Primary colonoscopic screening is considered to be of great benefit but also has the potential to cause severe harm. Thus, eligible subjects should be supported in making an informed choice whether to participate.

Objectives

To identify information on screening colonoscopy that colonoscopy-naïve subjects rate as particularly important for decision making.

Design

Survey of German statutory health insurance members using a written questionnaire in November 2015.

Study population

Colonoscopy-naïve individuals aged 50 to 65 years.

Main outcome measures

Importance of key information about screening colonoscopy, including potential risks and benefits, baseline risk of colorectal cancer/polyps and practical aspects of the procedure, as well as associations between participants' characteristics and their judgement of information as to being 'very important'.

Results

Of 1871 respondents (overall response rate: 31%), a subgroup of 370 colonoscopy-naïve subjects was eligible for inclusion (average age: 55 years, 47% male). Information on the risks was rated as very important by most respondents, unimportant by 6%. Information on the benefits was considered unimportant by 26%. Regression analysis showed that less educated persons regarded most items to be more often relevant than highly educated subjects. A greater proportion of women than men rated details regarding pain and practical aspects as very important. Subjects with a low educational level living alone were identified as the group with the least interest in information on risks.

Conclusion

Cultivating awareness around the central meaning of the (quantitative) benefits of screening in informed decision making should be focused on more in future information materials. The high requirement of less educated people to become more informed provides a strong motivation for further efforts to develop evidence-based information that adequately informs this group. Tailoring information according to gender-specific needs may be warranted in light of the observed differences in information preferences between women and men.



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Health-related quality of life, participation, and physical and cognitive function of patients with intensive care unit-acquired muscle weakness 1 year after rehabilitation in Germany: the GymNAST cohort study

Objective

To describe predictors for health-related quality of life, participation, physical activity and cognitive function in patients with intensive care unit (ICU)-acquired muscle weakness 1 year after discharge from rehabilitation.

Design

This is a cohort study.

Participants

We included 150 chronic critically ill individuals with ICU-acquired muscle weakness.

Setting

Postacute ICU and rehabilitation units in Germany.

Measures

We measured health-related quality of life using the EQ-5D, participation using the Reintegration of Normal Living Index, physical activity using the Physical Activity Scale for Individuals With Physical Disabilities, and basal cognitive function using the Montreal Cognitive Assessment (MoCA) at 6 months, and the Clock Drawing Test 6 and 12 months after discharge from postacute treatment. We described the predictors of the results at 12 months.

Results

The best predictors for good health-related quality of life 1 year after discharge were the time until regaining walking ability (OR=0.96, OR per day, 95% CI 0.93 to 0.99) and the mean MoCA score on admission to our postacute ICU and rehabilitation units (OR=1.25,95% CI 1.02 to 1.52).The best predictor for good participation 1 year after discharge was the MoCA sum score on admission to our postacute ICU and rehabilitation units (OR=0.85,95% CI 0.72 to 1.00). The best predictor for good physical activity 1 year after discharge was the Apache sum score on admission to our postacute ICU and rehabilitation units (OR=1.68,95% CI 0.89 to 3.13). The best predictor for normal cognitive function 1 year after discharge was regaining walking function in rehabilitation (OR=8.0,95% CI 0.49 to 13.69).

Conclusion

Recovery of health-related quality of life, participation, physical activity and basal cognitive function was still not complete 12 months after discharge from postacute treatment. We described the predictors for these important outcomes in participants with ICU-acquired muscle weakness 1 year after discharge from rehabilitation.

Trial registration number

DRKS00007181.



https://ift.tt/2zDCt31

Out-of-hospital endotracheal intubation experience, confidence and confidence-associated factors among Northern Japanese emergency life-saving technicians: a population-based cross-sectional study

Objective

Clinical procedural experience and confidence are both important when performing complex medical procedures. Since out-of-hospital endotracheal intubation (ETI) is a complex intervention, we sought to clarify clinical ETI experience among prehospital rescuers as well as their confidence in performing ETI and confidence-associated factors.

Design

Population-based cross-sectional study conducted from January to September 2017.

Setting

Northern Japan, including eight prefectures.

Participants

Emergency life-saving technicians (ELSTs) authorised to perform ETI.

Outcome measures

Annual ETI exposure and confidence in performing ETI, according to a five-point Likert scale. To determine factors associated with ETI confidence, differences between confident ELSTs (those scoring 4 or 5 on the Likert scale) and non-confident ELSTs were evaluated.

Results

Questionnaires were sent to 149 fire departments (FDs); 140 agreed to participate. Among the 2821 ELSTs working at responding FDs, 2620 returned the questionnaire (response rate, 92.9%); complete data sets were available for 2567 ELSTs (complete response rate, 91.0%). Of those 2567 respondents, 95.7% performed two or fewer ETI annually; 46.6% reported lack of confidence in performing ETI. Multivariable logistic regression analysis showed that years of clinical experience (adjusted OR (AOR) 1.09; 95% CI 1.05 to 1.13), annual ETI exposure (AOR 1.79; 95% CI 1.59 to 2.03) and the availability of ETI skill retention programmes including regular simulation training (AOR 1.31; 95% CI 1.02 to 1.68) and operating room training (AOR 1.44; 95% CI 1.14 to 1.83) were independently associated with confidence in performing ETI.

Conclusions

ETI is an uncommon event for most ELSTs, and nearly half of respondents did not have confidence in performing this procedure. Since confidence in ETI was independently associated with availability of regular simulation and operating room training, standardisation of ETI re-education that incorporates such methods may be useful for prehospital rescuers.



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Smartphone application for preventing depression: study protocol for a workplace randomised controlled trial

Introduction

Depression is the leading cause of life years lost due to disability. Appropriate prevention has the potential to reduce the incidence of new cases of depression, however, traditional prevention approaches face significant scalability issues. Prevention programmes delivered by via smartphone applications provide a potential solution. The workplace is an ideal setting to roll out this form of intervention, particularly among industries that are unlikely to access traditional health initiatives and whose workplace characteristics create accessibility and portability issues. The study aims to evaluate the effectiveness of a smartphone application designed to prevent depression and improve well-being. The effectiveness of the app as a universal, selective and indicated prevention tool will also be evaluated.

Methods and analysis

A multicentre randomised controlled trial, to determine the effectiveness of the intervention compared with an active mood monitoring control in reducing depressive symptoms (primary outcome) and the prevalence of depression at 3 months, with secondary outcomes assessing well-being and work performance. Employees from a range of industries will be invited to participate. Participants with likely current depression at baseline will be excluded. Following baseline assessment, participants, blinded to their allocation, will be randomised to receive one of two versions of the application: headgear (a 30-day mental health intervention) or a control application (mood monitoring for 30 days). Both versions of the app contain a risk calculator to provide a measure of future risk. Analyses will be conducted within an intention-to-treat framework using mixed modelling, with additional analyses conducted to compare the moderating effect of baseline risk level and depression symptom severity on the intervention's effectiveness.

Ethics and dissemination

The current trial has received ethics approval from the University of New South Wales Human Research Ethics Committee (HC17021). Study results will be disseminated through peer-reviewed journals and conferences.

Trial registration number

ACTRN12617000548336; Results.



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Evaluating the validity of the selection measures used for the UKs foundation medical training programme: a national cohort study

Objectives

Currently relative performance at medical school (educational performance measure (EPM) decile), additional educational achievements and the score on a situational judgement test (SJT) are used to rank applicants to the UK Foundation Years postgraduate medical training programme. We sought to evaluate whether these three measures were predictive of subsequent successful completion of the programme, and thus were valid selection criteria.

Methods

Data were obtained from the UK Medical Education Database (UKMED) on 14 131 UK applicants to the foundation programme starting in 2013 and 2014. These data included training outcomes in the form of Annual Reviews of Competency Progression (ARCPs), which indicated whether the programme was successfully completed. The relationship between applicants' performance on the three selection measures to the odds of successful programme completion were modelled.

Results

On univariable analyses, all three measures were associated with the odds of successful completion of the programme. Converting the SJT score to deciles to compare the effect sizes suggested that one decile increase in the EPM increased the odds of completing the programme by approximately 15%, whereas the equivalent value was 8% for the SJT scores. On multivariable analyses (with all three measures included in the model), these effects were only independently and statistically significant for EPM decile (OR 1.14, 95% CI 1.10 to 1.18, p<0.001) and SJT z-score decile (OR 1.05, 95% CI 1.01 to 1.09, p=0.02).

Conclusions

The EPM decile and SJT scores may be effective selection measures for the foundation programme. However, educational achievements does not add value to the other two measures when predicting programme completion. Thus, its usefulness in this context is less clear. Moreover, our findings suggest that the weighting for the EPM decile score, relative to SJT performance, should be increased.



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Which type of tobacco product warning imagery is more effective and sustainable over time? A longitudinal assessment of smokers in Canada, Australia and Mexico

Objective

This study examined smokers' responses to pictorial health warnings (PHWs) with different types of imagery under natural exposure conditions.

Methods

Adult smokers from online panels in Canada (n=2357), Australia (n=1671) and Mexico (n=2537) were surveyed every 4 months from 2012 to 2013. Participants were shown PHWs on packs in their respective countries and asked about: (1) noticing PHWs; (2) negative affects towards PHWs; (3) believability of PHWs; (4) PHW-stimulated discussions; and (5) quit motivation due to PHWs. Country-specific generalised estimating equation models regressed these outcomes on time (ie, survey wave), PHW imagery type (ie, symbolic representations of risk, suffering from smoking and graphic depictions of bodily harm) and interactions between them.

Results

In all countries, PHW responses did not significantly change over time, except for increased noticing PHWs in Canada and Mexico, increased negative affect in Australia and decreased negative affect in Mexico. For all outcomes, symbolic PHWs were rated lower than suffering and graphic PHWs in Canada (the only country with symbolic PHWs). Graphic PHWs were rated higher than suffering PHWs for negative affect (all countries), discussions (Canada) and quit motivation (Australia). Suffering PHWs were rated higher than graphic PHWs for noticing PHWs (Canada), believability (all countries), discussions (AustraliaandMexico) and quit motivation (Mexico). Changes in noticing, believability and discussions varied somewhat by imagery type across countries.

Conclusions

The different PHW imagery appears to have different pathways of influence on adult smokers. Reactions to specific PHWs are similar over 1–2 years, suggesting that wear-out of PHW effects is due to decreased attention rather than the diminishing effectiveness of content.



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Adult supraglottitis: a life-threatening disease and potential airway emergency

Description 

An 87-year-old woman was brought by ambulance to the emergency department (ED) with fever and dyspnoea. There was audible stridor, and the patient was noted to have a large left-sided submandibular swelling. She was in respiratory distress with a respiratory rate of 30. She was administered 100% oxygen. The on-call anaesthetics and ear, nose and throat (ENT) team were called emergently on arrival of the patient due to concern regarding possible impending airway compromise. A portable anteroposterior chest X-ray was performed on the patient on arrival to the ED as the cause of her dyspnoea was initially unclear. This showed marked upper airway narrowing (detail from the chest X-ray is depicted in figure 1). Only a venous blood gas was taken from the patient prior to intubation which showed acidosis with a pH of 7.31 and hypercarbia of 7.62 kilopascals.

Figure 1

Anteriorposterior radiograph...



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Two cases of high-output heart failure as initial presentation of iliac arteriovenous fistula

We present two cases of females in their 40s presenting with biventricular heart failure being the consequence of a large arteriovenous fistula. Both patients had undergone abdominal surgery several years prior to the heart failure event with the initial finding of moderate pulmonary hypertension and high-output heart failure. CT revealed a large arteriovenous fistula between the common iliac artery and vein which subsequently was closed percutaneously.



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Port-wine stain as a clue for two rare coexisting entities

Phakomatosis pigmentovascularis (PPV) is an uncommon dermatosis characterised by the presence of both pigmentary and vascular abnormalities.1 Its pathogenesis is not elucidated, and the prognosis is mainly determined by the presence of extracutaneous manifestations, such as Klippel-Trenaunay syndrome (KTS), that is defined by the triad of a port-wine stain (PWS), anomalous veins and progressive overgrowth of the affected extremity. Herein, we report a case of an adult patient, who presented with a large PWS, nevus of Ota, ocular melanosis, and limb hypertrophy and varicosities. These findings represented a rare association of PPV type IIb and KTS.



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Recurrent inflammatory myofibroblastic tumour of the lung: FDG PET/CT scan findings

Inflammatory myofibroblastic tumour (IMT) is a rare neoplasm, occurring most often in children and young adults. IMTs have intermediate biological behaviour with the chance of local invasion, recurrence and even distant metastasis. Wide range of clinical presentations makes the precise diagnosis of IMT more challenging. The best method for definitive diagnosis is tissue biopsy and newer imaging modalities including fleurodeoxyglucose (FDG) positron emission tomography (PET)/CT are useful tools in detection of disease recurrence or distant metastasis. Complete surgical resection is the best-known treatment for this tumour. Here we are presenting an IMT case in a 12-year-old girl in which her recurrent pulmonary IMT was diagnosed based on FDG PET/CT findings and referred for further salvage treatment. Overall imaging modalities are not specific, but PET/CT scan can be useful tool for evaluation of IMT regarding initial staging and restaging to assess treatment response and recurrence.



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Neonatal facial palsy, a case series: is CPAP the culprit?

We report a case series of three idiopathic unilateral facial nerve palsies in neonates with no identified risk factors. Neuroimaging done was normal. All the neonates had complete spontaneous recovery within a month, with no residual deficits. As per our knowledge, there are very few case reports of facial palsy in a neonate reported in literature and are often labelled as idiopathic.



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T-wave alternans: a harbinger for malignant ventricular arrhythmias

Description

A 50-year-old male chronic alcoholic presented to our emergency department with seizures and loss of consciousness after an alcoholic binge. He had no other significant medical history and was not on any regular medications. On examination, his pulse was 90 beats/min and his blood pressure was 80/60 mm Hg. His resting ECG showed sinus rhythm with QT prolongation. His serum sodium was 133 mmol/dL, potassium was 3.5 mmol/dL, magnesium was 1.4 mmol/dL and calcium was 6.6 mg/dL. The ECG demonstrated wide QRS tachycardia with a heart rate of approximately 200 beats/min and mild irregularity and morphology suggestive of polymorphic ventricular tachycardia initiated by a ventricular premature contraction falling on the terminal part of the T wave of the preceding sinus beat (figure 1A, black arrows). The postelectroversion tracing showed sinus rhythm at a rate of 55 beats/min, with alternating small, narrow (figure 1B, red arrows) and broad deep T-wave inversions (figure 1B, black...



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Acute presentation of a partially obstructing laryngeal tumour: adjuvant agents to gaseous induction of anaesthesia

We present the case of a 53-year-old man who attended our emergency department with stridor. He had recently undergone investigation for possible glottic cancer. We discuss the airway management of such a case. We believe this to be the first description of propofol target controlled infusion and clonidine to supplement a sevoflurane gas induction, in order to obtund response to intubation while maintaining spontaneous ventilation. We also consider how airway interventions may impact prognosis and need to be considered.



https://ift.tt/2JmCojO

E. coli strain engineering for the production of advanced biopharmaceutical products

Abstract
Since the emergence of the biopharmaceutical industry in the 1980's, Escherichia coli, has played an important role in the industrial production of recombinant proteins and plasmid DNA for therapeutic use. Currently, advanced biopharmaceutical products, including rationally designed recombinant proteins and viral-vector gene therapies, offer unprecedented promise for the long-term management, and even cure of disease. As such, E. coli remains an important production host for the biopharmaceutical industry. This review provides insight into the industrially relevant strain engineering approaches used to enhance both the quantity and quality of these therapeutic products.

https://ift.tt/2zzn8jU

Insights into the phylogeny of false-branching heterocytous cyanobacteria with the description of Scytonema pachmarhiense sp. nov. isolated from Pachmarhi Biosphere Reserve, India

Abstract
A false branching cyanobacterium (strain 10A1_PS) was isolated from a freshwater body of the Pachmarhi Biosphere Reserve, India and was characterised using the polyphasic approach. The detailed morphological examination indicated that the strain belonged to the complex genus Scytonema as it exhibited typical false branching character whose frequency increased with age of the culture. As the family Scytonemataceae and the genus Scytonema has been shown to be polyphyletic in many studies, we provide deep insights into the phylogenetic complexities within the family Scytonemataceae based on 16S rRNA gene phylogeny along with complete morphological, molecular and phylogenetic characterisation of the strain. The 16S rRNA gene phylogenetic tree inferred by Bayesian Inference, Neighbor-Joining and Maximum Parsimony methods showed that the strain clustered within the Scytonema sensu stricto clade. The phylogenetic distance and the positioning of the strain clearly indicated it to be different from other Scytonema species. Further analysis using rbcL phylogeny, folded secondary structures of the 16S-23S ITS, p-distance and percentage pairwise similarity matrix clearly distinguished the strain 10A1_PS from the other closely related species. In accordance with the International Code of Nomenclature for Algae, Fungi and Plants, we propose the name of the new species to be Scytonema pachmarhiense.

https://ift.tt/2mikvK0

The influence of sigma factors and ribosomal recognition elements on heterologous expression of cyanobacterial gene clusters in Escherichia coli

Abstract
Cyanobacterial natural products offer new possibilities for drugs and lead compounds but many factors can inhibit the production of sufficient yields for pharmaceutical processes. While Escherichia coli and Streptomyces sp. have been used as heterologous expression hosts to produce cyanobacterial natural products, they have not met with resounding success largely due to their inability to recognize cyanobacterial promoter regions. Recent work has shown that the filamentous freshwater cyanobacterium Anabaena sp. strain PCC 7120 recognizes various cyanobacterial promoter regions and can produce lyngbyatoxin A from the native promoter. Introduction of Anabaena sigma factors into E. coli might allow the native transcriptional machinery to recognize cyanobacterial promoters. Here, all 12 Anabaena sigma factors were expressed in E. coli and subsets were found to initiate transcription from several cyanobacterial promoters based on transcriptional fusions to the chloramphenicol acetyltransferase (CAT) reporter. Expression of individual Anabaena sigma factors in E. coli did not result in lyngbyatoxin A production from its native cyanobacterial gene cluster, possibly hindered by deficiencies in recognition of cyanobacterial ribosomal binding sites by native E. coli translational machinery. This represents an important step toward engineering E. coli into a general heterologous expression host for cyanobacterial biosynthetic gene cluster expression.

https://ift.tt/2uuIFVl

The unexpected diversity of microbial communities associated with black corals revealed by high-throughput Illumina sequencing

Abstract
The microbes associated with black corals remain poorly studied. The present study is the first attempt to investigate microbial community structure in the black corals Antipathes ceylonensis and A. dichotoma from the South China Sea by using high-throughput Illumina sequencing. A total of 52 bacterial and 3 archaeal phyla were recovered in this study, suggesting the black corals harboured highly diverse microbial communities. Among the 55 microbial phyla, Proteobacteria, Firmicutes, Bacteroidetes, Chloroflexi, Acidobacteria and Actinobacteria dominated in the two black corals from the South China Sea. Although most of the microbial phyla recovered from the two black corals have been reported in previous studies on coral-associated microbes, eight bacterial phyla including Synergistetes, Thermi, AncK6, GNO2, NKB19, NC10, WWE1 and GAL15, and the archaeal phylum Parvarchaeota are reported for the first time from corals in this study, which expands our knowledge about the diversity of coral-associated microbes. The comparison of microbial communities in the different black coral species indicated that A. ceylonensis harboured few abundant bacterial genera such as Citrobacter and Pseudomonas, whereas a high diversity of rare bacterial genera (<1% abundance), such as Winogradskyella and Rubricoccus, was detected only in A. dichotoma. These results suggested that the microbial community in black corals exhibited species-specific variation.

https://ift.tt/2mjHdkF

Detection of VBNC Vibrio cholerae by RT-Real Time PCR based on differential gene expression analysis

Abstract
The recognition of the viable but non-culturable (VBNC) state of pathogenic bacteria has brought with it many questions to answer related to the need to detect and quantify viable bacteria in the environment in an accurate way. To assess viability of Vibrio cholerae, we developed a RT-Real Time PCR technique based on differential expression analysis from mRNA deep sequencing data. We compared two induction conditions to achieve the VBNC state: a bacterial suspension induced by artificial seawater at 4°C, and the addition of 3',5'-cyclic diguanylic acid. The evaluation of the up-regulated genes in the induced bacterial samples was compared with a fresh culture in the mid-exponential phase. The data analysis was performed with the NOISeq R-package and revealed 17 up-regulated genes for induction condition I and 22 up-regulated genes for induction condition II. Only one region was found to be up-regulated for both induction conditions. The VCA0656 gene related to the aminoimidazole riboside kinase protein was detected as the most up-regulated region and used as a genetic marker to precisely detect the VBNC state in combination with the RT-Real Time PCR technique. This approach describes a novel method to differentiate the VBNC state of V. cholerae in water samples.

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Molecular diversity of fungal inhibitor cystine knot peptides evolved by domain repeat and fusion

Abstract
Peptides with the inhibitor cystine knot (ICK) motif are extensively present in animals and plants where they exert a diversity of biological functions. However, few studies have been undertaken on this class of peptides in fungi. In this work, we identify a total of 386 fungal ICK peptides and proteins containing this motif by computational data mining of fungal genome databases, which exhibit 14 different exon–intron structures. According to their domain architectures, these proteins are classified into three distinct structural types, including single domains, tandem repeat domains and fusion domains, in which six families belonging to single or tandem repeat domains show remarkable sequence similarity to those from animals and plants, suggesting their orthologous relationship. Extremely high molecular diversity in fungal ICKs might be attributable to different genetic mechanisms, such as gene/domain duplication and fusion. This work not only enlarges the number of ICK peptides in multicellular organisms, but also uncovers their complex evolutionary history in a specific lineage.

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Effect of gpd box copy numbers in the gpdA promoter of Aspergillus nidulans on its transcription efficiency in Aspergillus niger

Abstract
In this study, we characterised PgpdA, PgpdA2B, PgpdA3B and PgpdA4B promoters, containing 1–4 copies of gpd box by modifying the gpdA promoter, and constructed pSZHGX-xynB expression vectors, which were introduced into Aspergillus niger CICC2462 through Agrobacterium-mediated transformation. Thus, An (PgpdA-xynB), An (PgpdA2B-xynB), An (PgpdA3B-xynB) and An (PgpdA4B-xynB) homozygous recombinant strains were obtained. The xylanase activity of homozygous recombinant strains was measured. The enzymatic activities of An (PgpdA-xynB), An (PgpdA2B-xynB), An (PgpdA3B-xynB) and An (PgpdA4B-xynB) peaked on the 7th day of fermentation, at 1578.67, 2333.88, 3588.38 and 3183.51 U·mL−1, respectively. SDS-PAGE and qRT-PCR analysis indicated that An (PgpdA3B-xynB), containing three copies of gpd box, demonstrated the highest levels of protein expression and transcription. These results suggested that the PgpdA3B promoter promotes highly efficient transcription and may serve as a strong constitutive promoter for efficient recombinant protein expression. Additionally, a number of constitutive promoters with various transcription efficiencies were identified for the metabolic engineering of A. niger. Accordingly, this study provides a new approach for obtaining promoters with different transcription efficiencies.

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How persistent identifiers can save scientists time

Abstract
Research information is useful only if it can be shared—with other researchers, with research organizations (institutions, laboratories, funders and others), and with the wider community. In our digital age, that means sharing information between data systems. Persistent identifiers (PIDs) provide unique keys for people, places and things, which enables accurate mapping of information between these systems and supports the research process by facilitating search, discovery, recognition and collaboration. This article reviews the main PIDs used in research—digital object identifiers for publications, ORCID iDs for researchers, and a proposed new identifier for research organizations—as well as demonstrating how they are being used, and how, in combination, they can increase trust in research and the research infrastructure.

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Expression of miRNA-143 in Pancreatic Cancer and Its Clinical Significance

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


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The Role of Inflammatory Cytokines in Creating T Cell Exhaustion in Cancer

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


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Nuclear and Optical Bimodal Imaging Probes Using Sequential Assembly: A Perspective

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


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Contents



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Editors



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Mucosal exposure devices for colonoscopy: see the forest for the trees

The removal of adenomas at colonoscopy prevents colorectal cancers (CRC) and CRC deaths.1 Suboptimal detection of adenomas is associated with an increased risk of interval CRC and CRC death.2,3 Finally, improved detection of adenomas is associated with a reduced risk of interval CRC and death.4 This robust evidence has initiated efforts to improve endoscopists' skills in detecting adenomas.

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Response:

We thank Drs Wang et al1 for their interest in, and comments on, our study evaluating the safety and efficacy of lumen-apposing metal stents (LAMSs) with and without the simultaneous placement of double-pigtail stents (DPSs) for draining pancreatic pseudocysts (PPs).2 Similar to our results and similar to a multicenter study using LAMSs to drain PPs,3 these authors also observed cyst cavity infection in 10% of patients when LAMSs were used to drain PPs without the simultaneous placement of DPSs.

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Monitoring compliance with colorectal cancer screening: Do we have it covered?

Colorectal cancer (CRC) screening saves lives through prevention and early detection of cancer. In the United States, both CRC incidence and mortality are declining, and there is evidence that these encouraging trends partly reflect screening efforts over the past few decades.1 However, there remains room for improvement as screening rates still fall short of national goals.2 In the United States, greater use of programmatic screening relative to the more commonly used opportunistic approach would likely improve uptake.

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Focus on...



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In upcoming issues...



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ASGE update



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Information for readers



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Screening for esophageal varices in patients with hepatocellular carcinoma

Esophageal varices are identified in 10% to 40% of all patients with cirrhosis. Generally, they are most likely to be large and high risk in patients with advanced liver disease. Furthermore, the more severe portal hypertension is, the more likely are large varices to present. Several specific tests and systems have been developed with which to predict large varices, high-risk varices, or both. For example, platelet count, various blood tests and markers, spleen size, liver stiffness, spleen stiffness, and other measures have all been used.

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Duodenoscope-related and echoendoscope-related infections: Is “never” possible?

In 1999, the term "never event" was introduced by the National Quality Forum (NQF) to refer to particularly egregious and entirely preventable errors such as wrong-site surgery.1 The NQF more recently transitioned toward using the slightly more flexible term "serious reportable events" to describe events that are "unambiguous, usually preventable, serious," "indicative of a problem in a health care facility's safety systems," and/or "important for public credibility or…accountability."2 The widely reported duodenoscope-related outbreaks in the past several years, which have been associated with equipment from all 3 major endoscope manufacturers, meet the NQF criteria for "serious reportable events."

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The role of co-axially placed double-pigtail stents within lumen-apposing metal stents in draining pancreatic fluid collections

Aburajab et al1 reported their recent experience with lumen-apposing metal stents (LAMSs) in the treatment of pancreatic pseudocysts (PPs). They described a decreasing tendency in cyst cavity infection after placing double-pigtail stents (DPSs) across LAMSs compared with those without DPSs. Moreover, several centers reported their experience in DPS placement through LAMSs while draining walled-off necrosis (WON), and DPS was supposed to prevent occlusion by impacting necrotic tissue.2-4 Because PPs have no necrotic component, the authors postulate that DPSs might play a role in holding back the large pieces of solid food material from entering the cavity, which may subsequently lead to infection.

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Importance of timely eradication of Helicobacter pylori to prevent peptic ulcer recurrence and gastric cancer

Helicobacter pylori infection has long been identified as one of the most important risk factors for the development of peptic ulcer and gastric cancer. Eradication of H pylori infection has also been found to reduce the recurrence of peptic ulcers and lower the risk of gastric cancer.1-3 In the article in this issue of Gastrointestinal Endoscopy, Sverden et al4 report their results from a population-based study regarding the effect of delaying H pylori eradication on the risk of the development of recurrent peptic ulcer and gastric cancer.

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Antimicrobial decontamination of endoscopes: Are we there yet?

The growth of GI endoscopy provision globally has mirrored developments in the management of GI disease. Endoscopic procedures have become increasingly complex and are often performed in critically ill patients. All endoscopes have the potential to harbor and transmit pathogens, which could cause lethal healthcare-associated infections (HAIs). Data from the Centers for Disease Control and Prevention (CDC) suggest that the prevalence of HAIs has been on the decline.1 Endoscopy is generally safe, and HAIs associated with endoscopy have been uncommon despite the volume of procedures performed annually.

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Aspiring to inspIRE: catheter-directed electrical therapy and biliary metal stent patency

In the January issue of Gastrointestinal Endoscopy, Ueshima et al1 describe the feasibility and safety of catheter-directed irreversible electroporation (IRE) of a normal common bile duct (CBD) in an animal model. The authors report the results of their initial experience with a novel catheter (20 mm long, 7F) using a modified 240-cm balloon dilation catheter, which serves as a monopolar device to perform direct IRE at 2000 V, 90 pulses, and 100-μs pulse. On the basis of these preliminary results.

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Continuing Medical Education Exam: August 2018



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Table of Contents



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Editorial Board



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Caveolin-1 is dispensable for early lymphoid development, but plays a role in the maintenance of the mature splenic microenvironment

Caveolin-1 (CAV1) is known for its role as both a tumor suppressor and an oncogene, harboring a highly context-dependent role within a myriad of malignancies and cell types. In an immunological context, dysreg...

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Assessment of healthiness among long term inhabiting army soldiers in dry zone of Sri Lanka

Military personnel, because of the unique nature of their duties, are reluctant to face stressors. Living in hot and humid conditions they frequently suffer dehydration. Army soldiers living in dry zone of Sri...

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Determinants of condom use among parous women in North Central and South Western Nigeria: a cross-sectional survey

There appears to be an increasing trend of condom use for pregnancy prevention among nulliparous and multiparous women in developing countries. Drawing from a cross-sectional survey involving 1227 women select...

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A Model of Threatening Academic Environments Predicts Women STEM Majors’ Self-Esteem and Engagement in STEM

Abstract

The present study tested a model of threatening academic environments among a vulnerable population: women in science, technology, engineering, and mathematics (STEM) fields. Women in STEM are underrepresented and more likely to perceive their STEM educational environments as threatening than do men. U.S. Women majoring in STEM fields (n = 579) completed a questionnaire measuring each construct of a model of threatening academic environments proposed by Inzlicht et al. (2009). Supporting the model, greater gender stigma consciousness predicted greater gender-based rejection sensitivity. Gender rejection sensitivity predicted more negative perceptions of campus climate. More negative climate predicted more experiences of stereotype threat, which in turn predicted lower perceived control. Lower perceived control predicted greater disengagement from STEM domains, which predicted lower self-esteem. Differences also emerged between women in male- compared to female-dominated STEM subfields and between racial minority and majority women. This model describes how experiences of threatening environments may contribute to the underrepresentation of women in STEM. The model provides an overview for researchers, educators, and practitioners to better understand the relations among hostile STEM climates, experiences of identity threat, and academic disengagement. Interventions addressing environmental and individual factors in the model may improve retention and women's experiences in STEM.



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The oncometabolite D-2-hydroxyglutarate is an intercellular mediator in IDH-mutant gliomas that inhibits both complement and T cells

Purpose: Somatic mutations in the isocitrate dehydrogenase (IDH)-1 and -2 genes are remarkably penetrant in diffuse gliomas. These highly effective gain-of-function mutations enable mutant IDH to efficiently metabolize isocitrate to D-2-hydroxyglutarate (D 2-HG) that accumulates to high concentrations within the tumor microenvironment. D 2-HG is an intracellular effector that promotes tumor growth through widespread epigenetic changes in IDH mutant tumor cells, but its potential role as an intercellular immune regulator remains understudied. Experimental Design: Complement activation and CD4+, CD8+, or FOXP3+ T cell infiltration into primary tumor tissue were determined by immunohistochemistry using sections from 72 gliomas of World Health Organization (WHO) grade III and IV with, or without IDH mutations. Ex vivo experiments with D 2-HG identified immune inhibitory mechanisms. Results: IDH mutation associated with significantly reduced complement activation and decreased numbers of tumor-infiltrating CD4+ and CD8+ T cells with comparable FOXP3+/CD4+ ratios. D 2-HG potently inhibited activation of complement by classical and alternate pathways, attenuated complement-mediated glioma cell damage, decreased cellular C3b(iC3b) opsonization, and impaired complement-mediated phagocytosis. While D 2-HG did not affect dendritic cell differentiation or function, it significantly inhibited activated T cell migration, proliferation, and cytokine secretion. Conclusions:D 2-HG suppresses the host immune system, potentially promoting immune escape of IDH-mutant tumors.



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CORL Expression and Function in Insulin Producing Neurons Reversibly Influences Adult Longevity in Drosophila

CORL proteins (known as SKOR in mice, Fussel in humans and fussel in Flybase) are a family of CNS specific proteins related to Sno/Ski oncogenes. Their developmental and adult roles are largely unknown. A Drosophila CORL (dCORL) reporter gene is expressed in all Drosophila insulin-like peptide 2 (dILP2) neurons of the pars intercerebralis (PI) of the larval and adult brain. The transcription factor Drifter is also expressed in the PI in a subset of dCORL and dILP2 expressing neurons and in several non-dILP2 neurons. dCORL mutant virgin adult brains are missing all dILP2 neurons that do not also express Drifter. This phenotype is also seen when expressing dCORL-RNAi in neurosecretory cells of the PI. dCORL mutant virgin adults of both sexes have a significantly shorter lifespan than their parental strain. This longevity defect is completely reversed by mating (lifespan increases over 50% for males and females). Analyses of dCORL mutant mated adult brains revealed a complete rescue of dILP2 neurons without Drifter. Taken together, the data suggest that dCORL participates in a neural network connecting the insulin signaling pathway, longevity and mating. The conserved sequence and CNS specificity of all CORL proteins imply that this network may be operating in mammals.



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MEK Inhibition Induces Differentiation in RAS-Driven Rhabdomyosarcoma [Research Watch]

In fusion-negative rhabdomyosarcoma (FN-RMS), MEK inhibition relieves ERK2-mediated repression of MYOG.



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Natural Killer Cells Enhance Immune Checkpoint Blockade Efficacy [Research Watch]

Natural killer (NK) cell interactions with stimulatory dendritic cells (SDC) enhance immunotherapy.



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PI3K Inhibitor-Induced Insulin Feedback Activates PI3K Signaling [Research Watch]

Hyperinsulinemia drives resistance to PI3Kα inhibitors in tumors.



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Genomic Ribonucleotides Produce PARP-Trapping Lesions [Research Watch]

Mutations in RNASEH2B impair ribonucleotide excision repair to confer PARP inhibitor sensitivity.



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CDK12 Alterations Telling for Some with Prostate Cancer [News in Brief]

Patients with inactivating mutations in that gene may be more likely to respond to checkpoint inhibitor.



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Tensor Fasciae Suralis Muscle: Report of a Symptomatic Case With Emphasis on Imaging Findings

imageAbstract: We report a case of a symptomatic tensor fasciae suralis (TFS) muscle in an elite jumper, with a very rare tear in its origin. The TFS muscle must be recognized and differentiated from other pathologic entities in the popliteal region. The magnetic resonance imaging (MRI) and ultrasound (US) can reliably identify this variant and its pathology.

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Short Sleep and Adolescents' Performance on a Concussion Assessment Battery: An Experimental Sleep Manipulation Study

imageObjective: Correlational studies have linked short sleep to adolescents' report of postconcussion symptoms and cognitive performance during concussion assessments. This study tested whether those are cause–effect relationships. Design: Three-week randomly counterbalanced, within-subjects, crossover experiment. Setting: Adolescents slept at home with weekly visits to an outpatient clinic for sleep monitor uploads and outcome assessments. Participants: Twenty-four healthy 14- to 17.9-year-olds. Conditions: After an initial sleep-stabilization period, adolescents experienced 5-night spans of short sleep (SS; 6.5 hours/night in bed) versus Healthy Sleep Opportunity (HS; 9.5 hours/night in bed). Main Outcome Measures: Cognitive indexes and the postconcussion symptom scale (PCSS) from the Immediate PostConcussion Assessment and Cognitive Testing. Results: Adolescents reported significantly worse symptoms on the PCSS after SS than HS, even after excluding items manifestly related to sleep. Verbal memory was also worse after SS than HS, though the effect was small. The manipulation did not significantly affect other cognitive indexes. Conclusions: A realistic "dose" of short sleep, similar to what many adolescents experience regularly on school nights, can cause or contribute to symptom reports during concussion assessments. Consistent with previous sleep research, one-on-one cognitive tests seem to be less sensitive than measures of emotional and behavioral functioning to the effects of short sleep.

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Contrast-Enhanced Ultrasound as a New Investigative Tool in Diagnostic Imaging of Muscle Injuries—A Pilot Study Evaluating Conventional Ultrasound, CEUS, and Findings in MRI

imageObjective: To emphasize the diagnostic value of contrast-enhanced ultrasound (CEUS) in the imaging of muscle injuries with different degrees of severity by comparing findings to established imaging modalities such as conventional ultrasound and magnetic resonance imaging (MRI). Design: Case series. Setting: Institutional study. Conventional ultrasound and CEUS were performed in the Department of Internal Medicine. Magnetic resonance imaging was carried out in the Department of Radiology within the Magnetom Avanto 1.5T and Magnetom Skyra fit 3T (Siemens Healthineers, Erlangen, Germany) and in the Institution of Imaging Diagnostics and Therapy (Magnetom Avanto 1.5T; Siemens, Erlangen, Germany). Patients: Fifteen patients who underwent an acute muscle injury were recruited. Main Outcome Measures: The appearance and detectable size of muscle injuries were compared between each imaging modality. The injuries were assessed by 3 independent observers and blinded between imaging modalities. Results: All 15 injuries were identified on MRI and CEUS, whereas 10 injuries showed abnormalities in conventional ultrasound. The determination and measurement revealed significant differences between conventional ultrasound and CEUS depending on injury severity. Contrast-enhanced ultrasound revealed an impairment of microcirculation in grade I lesions (corresponding to intramuscular edema observed in MRI), which was not detectable using conventional ultrasound. Conclusions: Our results indicate that performing CEUS seems to be a sensitive additional diagnostic modality in the early assessment of muscle injuries. Our results highlight the advantages of CEUS in the imaging of low-grade lesions when compared with conventional ultrasound, as this was the more accurate modality for identifying intramuscular edema.

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Prevention of Ankle Sprain Injuries in Youth Soccer and Basketball: Effectiveness of a Neuromuscular Training Program and Examining Risk Factors

imageObjectives: The primary objective of this study was to examine the effectiveness of a neuromuscular training (NMT) warm-up program in reducing the risk of ankle sprain injury (ASI) in youth soccer and basketball. The secondary objective included the evaluation of risk factors for ASI. Study Design: Secondary analysis of pooled data from 5 studies. Participants: Male and female youth (11-18 years) soccer and basketball players (n = 2265) in Alberta, Canada. Outcome Measures: Ankle sprain injury was the primary outcome and was recorded using a validated prospective injury surveillance system consistent in all studies. The primary exposure of interest was NMT warm-up, which included aerobic, strength, agility, and balance components. Multivariable Poisson regression, controlling for clustering by team and offset for exposure hours, was used to estimate incidence rate ratios (IRRs) with 95% confidence intervals (CIs), with considerations for confounding and effect modification and evaluating all covariates as potential risk factors. Results: A total of 188 ASIs were reported in 171 players. Neuromuscular training significantly reduced the risk of ASI [IRR = 0.68 (95% CI; 0.46-0.99)]. Independent risk factors for ASI included previous ASI [IRR = 1.98 (95% CI; 1.38-2.81)] and participation in basketball versus soccer [IRR = 1.83 (95% CI; 1.18-2.85)]. Sex, age, body mass index, and previous lower extremity injury (without previous ASI) did not predict ASI (P > 0.05). Conclusions: Exposure to an NMT program is significantly protective for ASI in youth soccer and basketball. Risk of ASI in youth basketball is greater than soccer, and players with a history of ASI are at greater risk.

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Efficacy of Whole-Body Vibration Board Training on Strength in Athletes After Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Study

imageObjective: To evaluate whether an 8-week whole-body vibration training program may improve recovery of knee flexion/extension muscular strength in athletes after arthroscopic anterior cruciate ligament (ACL) reconstruction. Design: Randomized controlled trial. Setting: Single outpatient rehabilitation center. Participants: Thirty-eight female volleyball/basketball players (aged between 20 and 30), randomized into 2 treatment groups. Interventions: During a standardized six-month rehabilitation program, from week 13 to week 20 after surgery, the whole-body vibration group (n = 19) and the control group (n = 19) performed additional static knee flexor/extensor exercises on a vibration platform. For the whole-body vibration group, the vibration platform was set to 2.5 mm of amplitude and 26 Hz of frequency. The control group followed the same whole-body vibration board training with no vibrations. Main Outcome Measures: All patients were evaluated using an isokinetic strength test with a Biodex dynamometer at the beginning and at the end of the additional treatment protocol. The parameters tested were the peak torque and the maximum power of knee flexor and extensor muscles performing strength and endurance tests. Results: No vibration-related side effects were observed. Improvements were noticed in both groups, but increase in knee muscle isokinetic strength values was statistically significant in the whole-body vibration group when compared with the control group (differences in extension: peak torque 11.316/10.263 N·m and maximum power 13.684/11.211 W; flexion: peak torque 9.632/11.105 N·m and maximum power 10.158/9.474 W; P

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Pitch Counts in Youth Baseball and Softball: A Historical Review

imageObjective: Pitching injuries are getting increased attention in the mass media. Many references are made to pitch counts and the role they play in injury prevention. The original purpose of regulating the pitch count in youth baseball was to reduce injury and fatigue to pitchers. This article reviews the history and development of the pitch count limit in baseball, the effect it has had on injury, and the evidence regarding injury rates on softball windmill pitching. Data Source: Literature search through PubMed, mass media, and organizational Web sites through June 2015. Results: Pitch count limits and rest recommendations were introduced in 1996 after a survey of 28 orthopedic surgeons and baseball coaches showed injuries to baseball pitchers' arms were believed to be from the number of pitches thrown. Follow-up research led to revised recommendations with more detailed guidelines in 2006. Since that time, data show a relationship between innings pitched and upper extremity injury, but pitch type has not clearly been shown to affect injury rates. Current surveys of coaches and players show that coaches, parents, and athletes often do not adhere to these guidelines. There are no pitch count guidelines currently available in softball. Conclusions: The increase in participation in youth baseball and softball with an emphasis on early sport specialization in youth sports activities suggests that there will continue to be a rise in injury rates to young throwers. The published pitch counts are likely to positively affect injury rates but must be adhered to by athletes, coaches, and parents.

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Marijuana and Its Effects on Athletic Performance: A Systematic Review

imageObjective: To determine the effects of marijuana on athletic performance. Design: We searched MEDLINE, EMBASE, CINAHL, PsycINFO, AMED, and SPORTDiscus from their beginning to September 2016. Study quality was assessed using the Cochrane collaboration tool for assessing risk of bias and the Cochrane GRADE scale. No meta-analyses were performed for this review. Setting: Subjects in a track, gym, or recreational ward. Participants: Any primary study which included male and female adults of any athletic background between ages 18 and 65, with no other comorbid conditions. Interventions: Any primary study which used marijuana cigarettes and included a control group. Main Outcome Measures: Vital signs, pulmonary measures, physical work capacity, grip strength, and exercise duration were determined to be relevant outcomes. Results: Three trials examined marijuana and its effects on athletic performance. Two trials had a high risk of bias and 1 trial had an unclear risk of bias. The effect of marijuana on outcomes including heart rate, blood pressure, and exercise duration remains unclear. Low quality evidence suggests that treatment, sham, and inactive control groups do not have a significant difference for grip strength. Low quality evidence suggests that there is an ergogenic effect of treatment demonstrated by increased bronchodilation and FEV1 compared with inactive control and that there is an ergolytic effect of treatment demonstrated by decreased physical work capacity compared with sham and inactive control groups. Conclusion: Because the number and quality of studies was low, the effects of marijuana on athletic performance remain unclear.

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Unusual Cause of Thoracic Wall Pain in a Kayaker: A Case Report

imageAbstract: Chest wall injuries are common in paddle-based sports such as kayaking. We present the case of a 46-year-old amateur kayaker who presented with signs and symptoms in keeping with a rib stress response or fracture. The patient failed to respond to conservative management and subsequent imaging revealed an obstructed left kidney with associated hydronephrosis. This case report highlights the importance of considering the wider differential diagnoses when managing athletes participating in paddle-based sports, especially when symptoms fail to settle with appropriate conservative management.

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Functional Movement Screening and Injury Rates in High School and Collegiate Runners: A Retrospective Analysis of 3 Prospective Observational Studies

imageObjective: Determine if the Functional Movement Screening (FMS) can be used to predict injury in high school and collegiate cross-country and track runners. Design: Prospective Observational, Cohort Study, Level of Evidence, 2. Setting: High schools and colleges in the Central Ohio area. Patients: Inclusion: (1) cross-country or track runners at participating schools; (2) full participation without restrictions; and (3) signed informed assent or consent. Exclusion: (1) Any injury or lower extremity surgery within 30 days; (2) planned limited participation in the upcoming season; or (3) other participation restrictions. Interventions: Functional Movement Screening was completed before the start of each season. Injuries were tracked during the regular season. No interventions were made based on FMS score. Main Outcome Measures: Functional Movement Screening scores, including overall, lower extremity, and specific exercises were compared between runners who did and did not sustain an injury using 2 sample t tests. A cutoff FMS score of ≤14 (most common in previous studies), and ≤15 (determined by a receiver operating characteristic curve), were compared using χ2 tests. Results: One hundred eighty-three runners were enrolled in the study. Overall, 32 (17.5%) runners sustained an injury. Functional Movement Screening score was not accurate in predicting injury for ≤14 (sensitivity: 65.6%; specificity: 39.7%; and area under the curve = 0.501) or ≤15 (sensitivity: 84.4% and specificity: 23.8%). There was no difference in risk of injury for runners with a FMS score of ≤14 (15.5%) and >14 (18.8%) (P = 0.572) or with a FMS score of ≤15 (17.5%) and >15 (17.4%) (P = 0.988). Conclusions: Functional Movement Screening composite score may not be useful for injury prediction in populations of high school and collegiate runners.

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Is There a Relationship Between the Functional Movement Screen, Star Excursion Balance Test, and Balance Error Scoring System?

imageObjective: To evaluate associations between the Functional Movement Screen (FMS), Star Excursion Balance Test (SEBT), and Balance Error Scoring System (BESS) scores. Design: Correlational. Setting: College athletic training facilities. Participants: Fifty-two intercollegiate athletes (men = 36 and women = 16) representing 8 sports and cleared for unrestricted sport participation. Interventions: Participants completed the FMS, SEBT, and BESS, in random order, during 1 testing session. Testing order was randomized to control for fatigue and learning effects. Main Outcome Measures: Composite and item scores for the FMS, SEBT, and BESS. Results: A fair, negative correlation was found between FMS asymmetry and SEBT composite (r = −0.31, P = 0.03) scores. Fair, positive correlations were reported for FMS rotary stability task and SEBT anterior (r = 0.37-0.41, P ≤ 0.007) and posteromedial (r = 0.31, P = 0.03) reaches. Fair, negative correlations were reported for FMS deep squat and BESS single-leg firm (r = −0.33, P = 0.02), double-leg foam (r = −0.34, P = 0.02) and tandem foam (r = −0.40, P = 0.003), FMS inline lunge and BESS single-leg firm (r = −0.39, P = 0.004), FMS trunk stability pushup and tandem foam (r = −0.31, P = 0.025), and FMS composite and BESS single-leg firm (r = −0.37, P = 0.007). Little-to-no correlations were reported for remaining comparisons. Conclusions: Results indicate that each instrument provides distinct information about function, with only small areas of overlap. Associations between the FMS asymmetry score and SEBT composite score may indicate a relationship between movement asymmetry and postural stability. Associations between the FMS deep squat and BESS foam tasks may be related to underlying neuromuscular control factors.

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Multidisciplinary Assessment of 100 Athletes With Groin Pain Using the Doha Agreement: High Prevalence of Adductor-Related Groin Pain in Conjunction With Multiple Causes

imageObjective: To examine the prevalence of different causes of groin pain in athletes using the recent Doha consensus classification of terminology and definitions of groin pain in athletes. Design: Descriptive epidemiological study. Setting: Multidisciplinary sports groin pain clinic at Aspetar Orthopedic and Sports Medicine Hospital, Doha, Qatar. Patients: The clinical records of 100 consecutive athletes with complaints of groin pain who attended the multidisciplinary sports groin pain clinic between January and December 2014 were analyzed. Main Outcome Measures: The causes of groin pain were categorized according to terminology and definitions agreed upon at the Doha consensus meeting on groin pain classification in athletes. The classification system has 3 main subheadings; defined clinical entities for groin pain (adductor-related, iliopsoas-related, inguinal-related, and pubic-related groin pain), hip-related groin pain, and other causes of groin pain in athletes. Results: The majority of athletes were male (98%) soccer players (60%). Multiple causes for groin pain were found in 44% of the athletes. Adductor-related groin pain was the most prevalent defined clinical entity (61% of athletes), and pubic-related groin pain was the least prevalent (4% of athletes). Conclusions: Adductor-related groin pain is the most commonly occurring clinical entity in this athlete population in mainly kicking and change of direction sports and frequently, multiple causes are found. Clinical Relevance: This is the first study to use the Doha agreement classification system and highlights the prevalence of adductor-related groin pain and that often multiple clinical entities contribute to an athlete's groin pain. Consequently, prevention programs should be implemented with these factors in mind.

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Predictors of the Biomechanical Effects of Customized Foot Orthoses in Adults With Flat-Arched Feet

imageObjective: To determine the potential presence and characteristics of biomechanical responders to customized foot orthoses during walking in adults with flat-arched feet. Design: Experimental, repeated-measures. Setting: University clinic and laboratory. Participants: Eighteen symptom-free adults with flat-arched feet. Interventions: Customized foot orthoses. Main Outcome Measures: In-shoe foot biomechanics were measured during walking with and without customized foot orthoses using 3D analysis. Selected kinematic and kinetic variables during baseline walking were compared between subgroups who displayed reductions in calcaneal eversion with foot orthoses to those with no change or increases. Results: Biomechanical responders displayed significantly greater peak calcaneal eversion (+2.2 degrees, P = 0.009). Time to peak calcaneal eversion (−11%, P = 0.006), peak dorsiflexion of the hallux (−6 degrees, P = 0.001), and medial–lateral excursion of the center of pressure during loading response were all reduced in the responder subgroup (−2 mm, P ≤ 0.001). Variables significantly different between subgroups were moderately associated with the response to foot orthoses (canonical correlation = 0.687, effect size = 0.47, P = 0.063). Conclusions: Individuals with increased dynamic foot pronation were more likely to show a favorable biomechanical response to customized foot orthoses, providing preliminary evidence to support the stratified use of foot orthoses to optimize their effectiveness.

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Differences in Athletic Performance Between Sportsmen With Symptomatic Femoroacetabular Impingement and Healthy Controls

imageObjective: Femoroacetabular impingement (FAI) is a commonly recognized condition in athletes characterized by activity-related hip pain and stiffness, which if left untreated can progress to hip osteoarthritis. The aim of the study was to determine the effect of symptomatic FAI on performance in young athletes based on the hypothesis that athletes with FAI would show deficits in performance compared with healthy controls. Design: The functional performance of a cohort of preoperative, competitive sportsmen with symptomatic FAI (FAI group, n = 54), was compared with that of a group of age, sex and activity-level matched controls (n = 66). Outcome Measures: Participants performed functional tests including a 10-m sprint, a modified agility T-test, a maximal deep squat test and a single-leg drop jump (reactive strength index). Hip range of motion was assessed by measuring maximal hip flexion, abduction, and internal rotation (at 90 degree hip flexion). Results: The FAI group was significantly slower during the 10-m sprint (3%, P = 0.002) and agility T-test (8%, P

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Epidemiology of Injuries in Women's Lacrosse: Implications for Sport-, Level-, and Sex-Specific Injury Prevention Strategies

imageObjective: By the end of 2013, the United States had an estimated 278 000 female lacrosse players, with half of those participating at the youth level. The effects of the sport's rapid growth on injury rates have yet to be determined. The purpose of this clinical review is to synthesize the available published data on injuries that have occurred in the sport of women's lacrosse. Of particular interest was the risk of injury based on the level of play and position. Data Sources: A comprehensive literature search was performed in PubMed, High Wire Press, SPORTDiscus, Google Scholar, and Ovid using the keywords "Lacrosse Injuries," "Epidemiology Lacrosse Injuries," "Lacrosse Injury," "Lacrosse," and "Injury." Study Selection: The electronic search included material published during or after 1950. In addition, all bibliographies of electronically found sources were cross-referenced to identify any additional publications that were not produced in the electronic searches. Data Extraction: All articles with data on women's injury rates were categorized by overall injury rates, rates by session (competition vs practice), nature of injury, location, type, severity, and player position. Data Synthesis: Injury rates increase with age: from youth leagues to high school and finally to the collegiate level. Rates of injury varied from 0.03 to 3.9 injuries/100 athletes. Women's game injury rates are consistently higher than practice injury rates (ranging from 0.2 to 7.1 vs 0.01 to 3.3). Injuries occur most frequently from stick-to-player or player-to-ball contact, rather than player-to-player contact. Women sustain a higher percentage of head and facial injuries relative to male lacrosse players. The most common types of injuries for women are concussions, sprains, contusions, and lacerations. More than half of all injuries are in the mild category resulting in players missing practice and games for 1 to 7 days. Offensive players had the most injuries, followed by defensive players and then midfielders, with goalies having the fewest number of injuries. Conclusions: In women's lacrosse, the rules and equipment used are substantially different than for the men's game. Face and hand injuries are more prevalent for women when compared with men, and ankle injuries are most prevalent in female youth. Medical professionals who treat lacrosse players can benefit from an improved understanding of the types and rates of the injuries they are likely to encounter. Improved awareness of lacrosse-specific injuries can assist these professionals to be more prepared to treat these athletes, which may lead to improved care and outcomes.

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“Recognize and Remove”: A Universal Principle for the Management of Sports Injuries

imageObjective: To identify the locations and types of injury that result in players not being immediately removed from the field of play when injured and to quantify the magnitude of the situation. Design: Prospective cohort epidemiological study with definitions and procedures compliant with the international consensus statement for studies in rugby. Setting: Sevens World Series (SWS) (2008-2016) and Rugby World Cup (RWC) (2007, 2011, 2015). Participants: Players from 17 countries taking part in the SWS and 22 countries taking part in the RWC. Main Outcome Measures: Location, type, and mean severity of injury, period of match when the injury occurred and whether players were removed from the field of play when injured. Results: Injured players (51.5%) in the SWS and 33.1% of injured players in the RWC were immediately removed from the field of play at the time of injury. The percentages of players immediately removed varied from 16.7% for hand fractures (severity: 71 days) to 96.7% for shoulder dislocations/subluxations (severity: 105 days) during the SWS and from 4.5% for shoulder ligament sprains (severity: 25 days) to 65.9% for concussions (severity: 9 days) during the RWC. The percentage of players immediately removed from play when injured was not related to the severity of the injury sustained. Conclusions: A high proportion of players continue to play (in the same game) after sustaining an injury although the likelihood of being removed from play is not dependent on injury severity.

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Low-Intensity Pulsed Ultrasound Therapy for a Symptomatic Persistent Olecranon Physis in an Adolescent Baseball Pitcher

imageAbstract: A 15-year-old competitive right-handed high school baseball pitcher experienced an acute onset of right elbow pain when throwing. He initially treated it conservatively with rest alone for 3 months, but on return to throwing, he was still experiencing pain. Radiographs revealed that he had a persistent olecranon physis. He proceeded with a trial of low-intensity pulsed ultrasound therapy and attained radiographic evidence of bony union at 7 months postinjury, thus avoiding surgical intervention. He returned to pitching competitively 9 months after injury without elbow pain. This is the first reported case of using ultrasound bone stimulation for treatment of a symptomatic persistent olecranon physis in a baseball pitcher.

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Rock Climbing–Related Bone Marrow Edema of the Hand: A Follow-up Study

imageObjective: Sport climbers strain passive and active anatomical structures of their hands and fingers to the maximum during training or competition. This study was designed to investigate bone marrow edema (BME) in rock climbing athletes. Design: Systematic detection, treatment, and follow-up investigation of rock climbing athletes with BME of the hand. Setting: Primary-level orthopedic surgery and sports medicine division of a large academic medical center. Patients: Thirty-one high-level climbers with diffuse pain in the hand and wrist joint caused by rock climbing were included in this study. Interventions: The therapy consisted of consequent stress reduction and a break from sports. Main Outcome Measures: Reduction of BME shown through magnetic resonance imaging (MRI) and regaining of preinjury climbing levels (Union Internationale des Associations d' Alpinisme metric scale). Results: In 28 patients, MRI revealed osseous edema because of overload at the respective area of interest, mainly in the distal radius, the distal ulna, or the carpal bones, which could not be otherwise diagnosed as inflammations, tumors, or injuries. We classified these edemas and fractures of the hamate because of overload. The edema was a stress reaction to highly intensive training and climbing with presumably high traction to the wrist area. The control MRIs demonstrated that even with a consequent stress reduction, the edemas required 3 to 4 months to disappear completely. Conclusions: Climbers with nonspecific, diffuse pain in the wrist and/or the fingers should be examined with MRI to detect or exclude the diagnosis of a BME.

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A Rare Presentation of a Morel-Lavallee Lesion of the Lower Leg Successfully Treated With Ultrasound-Guided Aspiration

imageAbstract: A Morel-Lavallee lesion (MLL) is a relatively rare condition that is caused by a traumatic shearing force. This force leads to a closed degloving injury of the subcutaneous tissue and fascia that creates a potential space that can fill with lymph, blood, and necrotic fat. The MLLs are traditionally seen after high impact trauma and typically located at the greater trochanter and pelvis, although recent reports have found them to be located at the knee, thigh, and lower leg. The MLLs typically present as swelling at the site of injury, which can be difficult to differentiate from several other diagnoses. This case report discusses an MLL in the lower extremity that occurred during a rugby game. A lack of familiarity with MLLs often leads to delayed diagnosis and treatment. The diagnosis was eventually made with an magnetic resonance imaging, and the lesion was successfully treated with ultrasound-guided aspiration and compression. The athlete was able to return to play without recurrence of the lesion.

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Role of microRNA-218-5p in the pathogenesis of chronic obstructive pulmonary disease

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease characterized by inflammatory cell activation and the release of inflammatory mediators. By measuring microRNA expression in the plasma of COPD subjects, we aimed to identify the clinical relevance of plasma miRNA levels in these patients.

PATIENTS AND METHODS: A total of 40 COPD patients and 40 healthy controls were enrolled in the study. The COPD model of C57BL/6 mice was also developed by exposing them to cigarette smoke (CS). The expression of microRNA-218-5p was detected by qRT-PCR in all the subjects and mice. The serum level of IL-18 and TGF-β1 was also detected via ELISA kit. To investigate the effects of miR-218-5p, 10 mg/kg of miR-218-5p inhibitor (miR-218-5p antagonist), a scrambled control or PBS (solvent) was intranasally administered on the first and the fourth exposure day, before the start of CS exposure.

RESULTS: The results showed that miR-218-5p was significantly down-regulated in patients with COPD, compared to normal subjects. There was a negative correlation between the plasma miR-218-5p level and the duration of disease since diagnosis in COPD ex-smokers. CS-induced COPD mice experiments with a miR-218-5p inhibitor demonstrated a protective role of miR-218-5p in cigarette smoke-induced inflammation and COPD.

CONCLUSIONS: These findings supported that miR-218-5p may, therefore, play an important role in the pathogenesis of COPD.

L'articolo Role of microRNA-218-5p in the pathogenesis of chronic obstructive pulmonary disease sembra essere il primo su European Review.



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Comorbidities in coexisting chronic obstructive pulmonary disease and obstructive sleep apnea – overlap syndrome

OBJECTIVE: Chronic Obstructive Pulmonary Disease (COPD) and Obstructive Sleep Apnea (OSA) are separately associated with several comorbidities. The coexistence of the two diseases, referred to as overlap syndrome, may act as a predisposing factor for a higher prevalence of comorbidities compared to those associated with each disease separately. The objective of the study was to evaluate the relative prevalence of cardiovascular as well as other comorbidities, in patients with the overlap syndrome, as compared to patients that are diagnosed solely with OSA.

PATIENTS AND METHODS: We examined thirty-eight (38) patients (27 men, 11 women) with coexisting COPD and OSA – overlap syndrome (Group 1) vs. 38 patients with OSA-only (Group 2), matched for sex, age, and Body Mass Index (BMI). All patients underwent pulmonary function tests (PFTs), oximetry and overnight polysomnography and were asked about other coexisting chronic diseases and medications.

RESULTS: The two groups differed significantly, as expected, in PFTs (Forced Vital Capacity – FVC, p=0.005, Forced Expiratory Volume in 1 s – FEV1, p<0.001) and in daytime oximetry (p=0.007). Three (3) overlap (7.89%) and 9 OSA patients (23.69%) had no other known diseases. All others suffered from 1 – ≥ 4 comorbidities. Overlap patients suffered more often from multiple (≥ 4) comorbidities than OSA-only patients (11, 28.95% vs. 4, 10.52%, respectively). The most common coexisting diseases were hypertension (50% vs. 42.1%), cardiovascular disease (CVD) (44.74% vs. 26.31%), diabetes mellitus (DM) (28.95% vs. 13.16%), dyslipidemia (21.05% vs. 26.31%) and depression (7.89% vs. 13.16%).

CONCLUSIONS: We conclude that comorbidities, especially cardiovascular, in patients with overlap syndrome are at least as prevalent as in sleep apneic only patients and may contribute to the overall severity and prognosis of the disease.

L'articolo Comorbidities in coexisting chronic obstructive pulmonary disease and obstructive sleep apnea – overlap syndrome sembra essere il primo su European Review.



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Jury Awards $4.62B in Johnson & Johnson Talcum Powder Lawsuit

FRIDAY, July 13, 2018 -- A jury says Johnson & Johnson must pay $4.62 billion to 22 women who allege they developed ovarian cancer after using the company's Baby Powder and Shower to Shower brand talcum powder as part of their daily feminine...

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Fish Pedicure Causes Woman to Lose Toenails

FRIDAY, July 13, 2018 -- A woman lost several toenails after a fish pedicure, according to a case report published online July 3 in JAMA Dermatology. Shari R. Lipner, M.D., Ph.D., from Weill Cornell Medicine in New York City, reports on a young...

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Virtual Assistants Not HIPAA Compliant

FRIDAY, July 13, 2018 -- Virtual assistant programs like Google Assistant, Siri, and Alexa are not yet in compliance with the Health Insurance Portability and Accountability Act (HIPAA), warns an article published in Medical Economics. While it is...

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100 Now Sickened by Salmonella-Tainted Honey Smacks Cereal

FRIDAY, July 13, 2018 -- One hundred people across 33 states have now fallen ill with Salmonella after eating Kellogg's Honey Smacks cereal, according to the U.S. Centers for Disease Control and Prevention. Many of the illnesses linked to the...

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Data Support FDA Restrictions on Child Cough and Cold Medicines

FRIDAY, July 13, 2018 -- New research supports expanded restrictions on opioid-containing cough and cold medications (CCMs) for children, according to a short communication published recently in Clinical Toxicology. Ian M. Paul, M.D., from the Penn...

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Ipomoea batatas L. Lam. ameliorates acute and chronic inflammations by suppressing inflammatory mediators, a comprehensive exploration using in vitro and in vivo models

Ipomoea batatas L. Lam. is a functional food and belongs to family Convolvulaceae. It is used as an antiinflammatory, aphrodisiac, antiasthmatic, anticonvalescent, antitumor, antanemic and antidiabetic agent by l...

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Effective antioxidant, antimicrobial and anticancer activities of essential oils of horticultural aromatic crops in northern Egypt

Identifying ornamental plants as new natural antioxidant and antimicrobial sources is always of great importance for the ornamental and horticultural industries.

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The prevention of 2,4-dinitrochlorobenzene-induced inflammation in atopic dermatitis-like skin lesions in BALB/c mice by Jawoongo

Jawoongo is an herbal mixture used in traditional medicine to treat skin diseases. This study aimed to investigate whether Jawoongo ameliorates Atopic dermatitis (AD)-like pathology in mice and to understand i...

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An update on the management of pancreatic neuroendocrine tumors

imagePancreatic neuroendocrine tumors (PNETs) are a rare and heterogeneous group of neoplasia and differ in their clinical presentation, behavior, and prognosis based on both histological features and cancer stage at the time of diagnosis. Although small-sized tumors can be surgically resected, locally advanced and metastatic tumors confer a poor prognosis. In addition, only limited treatment options are available to the latter group of patients with PNETs, such as hormonal analogs, cytotoxic agents, and targeted therapy. In selected patients, liver-directed therapies are also used. As expected, clinicians taking care of these patients are challenged to develop an effective and comprehensive treatment strategy for their patients amid a wide variety of treatment modalities. Targeted therapy for PNETs is limited to sunitinib and everolimus. Presently, a number of clinical studies are ongoing to assess the efficacy of newer targeted agents alone and in combination with previous agents for the treatment of advanced PNETs. The authors reviewed the current treatment and also discussed the emerging agents and emphasized the need to identify biomarkers.

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Continuous low-dose infusion of patupilone increases the therapeutic index in mouse and rat tumour models

imagePatupilone is a microtubule-targeted cytotoxic agent with clinical efficacy, but causes diarrhoea in more than 80% of patients. The efficacy and tolerability of patupilone delivered continuously by subcutaneous (s.c.) mini-pumps [(mini-pump dose (MPD)] or by intravenous bolus administration [intravenous bolus dose (IVBD)] were compared preclinically to determine whether the therapeutic index could be improved. The antiproliferative potency in vitro of patupilone was determined by measuring total cell protein. Tumours were grown s.c. in rats (A15) or nude mice (KB31, KB8511) or intracranially in nude mice (NCI-H460-Luc). Efficacy was monitored by measuring tumour volumes, bioluminescence or survival. Toxicity was monitored by body weight and/or diarrhoea. Total drug levels in blood, plasma, tissues or dialysates were quantified ex-vivo by liquid chromatography–mass spectroscopy/mass spectroscopy. Patupilone was potent in vitro with GI50s of 0.24–0.28 nmol/l and GI90s of 0.46–1.64 nmol/l. In rats, a single IVBD of patupilone dose dependently inhibited the growth of A15 tumours, but also caused dose-dependent body weight loss and diarrhoea, whereas MPD achieved similar efficacy, but no toxicity. In mice, MPD showed efficacy similar to that of IVBD against KB31 and KB8511 tumours, but with reduced toxicity. In a mouse intracranial tumour model, IVBD was more efficacious than MPD, consistent with patupilone concentrations in the brain. MPD provided constant plasma levels, whereas IVBD had very high C0/Cmin ratios of 70–280 (rat) or 8000 (mouse) over the dosing cycle. Overall, the correlation of plasma and tumour levels with response indicated that a Cave of at least GI90 led to tumour stasis. Continuous low concentrations of patupilone by MPD increased the therapeutic index in s.c. rodent tumour models compared with IVBD by maintaining efficacy, but reducing toxicity.

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Biochemistry of N-mustard tumour control compounds reconsidered

imageThe biochemicals and reactions involved in the present mechanism of degradation of tumour cells during chemotherapy are reconsidered and limitations noted. Alternative mechanisms and treatment methods are detailed.

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Growth arrest and apoptosis induced by kinesin Eg5 inhibitor K858 and by its 1,3,4-thiadiazoline analogue in tumor cells

imageTumors are complex and heterogeneous but, despite this, they share the ability to proliferate continuously, irrespective of the presence of growth signals, leading to a higher fraction of actively growing and dividing cells compared with normal tissues. For this reason, the cytotoxic antimitotic treatments remain an important clinical tool for tumors. Among these drugs, antitubulin compounds constitute one of the most effective anticancer chemotherapies; however, they cause dose-limiting side effects. Therefore, it is still necessary to develop compounds with new targets and new mechanisms of action to reduce side effects or chemoresistance. Mitosis-specific kinesin Eg5 can represent an attractive target for discovering such new anticancer agents because its role is fundamental in mitotic progression. Therefore, we analyzed the effects induced by an inhibitor of kinesin Eg5, K858, and by its 1,3,4-thiadiazoline analogue on human melanoma and prostate cancer cell lines. We found that both compounds have an antiproliferative effect, induce apoptosis, and can determine a downmodulation of survivin.

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Effect of pyruvate kinase M2-regulating aerobic glycolysis on chemotherapy resistance of estrogen receptor-positive breast cancer

imageThis study aims to explore the effect and mechanism of pyruvate kinase M2 (PKM2) on chemotherapy resistance of estrogen receptor-positive breast cancer (ER+ BC) by regulating aerobic glycolysis. The expression of PKM2 in ER+ BC MCF-7 cells, T47D cells and MCF-7/ADR cells (which are subject to adriamycin/ADR induction) were determined by quantitative real-time PCR and western blot. MCF-7/ADR (M/A) cells were grouped into blank group (M/A), negative group (M/A+NC), low expression of PKM2 group (M/A+si-PKM2 group), overexpression of PKM2 group (M/A+PKM2 group) and glycolysis inhibition group (M/A+PKM2+2-DG group). Quantitative real-time PCR and western blot were applied to measure the expressions of PKM2, multidrug resistance, and glutathione-S-transferase π. Glucose and lactic acid kit was used to detect the amount of glucose uptake and lactic production. Cell variability, clone formation ability, and cell apoptosis were respectively measured by MTT, clone formation assay, and flow cytometry. Transwell assay and scratch assay were applied for cell invasion and migration ability. By overexpressing PKM2 in MCF-7 and T47D cells and using 2-DG, the effect on sensitivity of adriamycin amycin was explored. MCF-7/ADR cells have both elevated mRNA and protein expressions of PKM2 when compared with MCF-7 cells (both P

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The outcome to axitinib or everolimus after sunitinib in metastatic renal cell carcinoma

imageWe aimed to investigate the different outcomes in patients with metastatic renal cell carcinoma treated with second-line axitinib or everolimus after sunitinib. Patients treated in 16 oncological centres in Italy were included, and those receiving axitinib or everolimus from January 2013 onwards were analysed for outcomes. Descriptive statistical tests were used to highlight differences between groups. The Kaplan–Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Data on 634 patients with metastatic renal cell carcinoma treated with first-line sunitinib have been obtained. A total of 182 patients received a second-line therapy with everolimus (79 patients, 43%) or axitinib (103 patients, 57%), respectively. The median PFS was 4.6 [95% confidence (CI): 2.6–6.5] months for patients treated with everolimus and 5.5 (95% CI: 4.3–6.7) months for patients treated with axitinib (P=0.7). The median OS was 13.9 (95% CI: 10.4–17.4) months for patients treated with everolimus and 12.0 (95% CI: 7.9–16.2) months for patients treated with axitinib (P=0.3). No differences were found based on length of first-line treatment. Major limitations are the retrospective nature of the study and the lack of a prospective evaluation of the progression. This study reports no significantly differences between everolimus and axitinib in terms of both PFS and OS. Furthermore, the length of first-line treatment cannot be used as such a predictive factor and cannot suggest the use of a molecule compared with another.

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