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Τρίτη 15 Μαΐου 2018

Peri-operative therapy for operable gastroesophageal adenocarcinoma; past, present and future

Abstract
Surgery represents the only chance of cure for patients with gastroesophageal adenocarcinoma; however surgery alone does not cure most patients. Over the past decade, several multimodality adjunctive treatments have improved survival for patients with operable gastroesophageal adenocarcinoma who are undergoing surgical resection; these include peri-operative chemotherapy, neoadjuvant chemoradiotherapy, adjuvant chemotherapy and adjuvant chemoradiotherapy. More recently, the results of several large randomised trials are leading to a shift in the peri-operative treatment of gastroesophageal cancer, away from anthracycline-based and towards taxane-based chemotherapy regimens. Emerging data supports an increased focus on patients who are at high risk for poor operative outcomes such as R1 resection, and on patients who are at high risk for relapse following surgery such as those with lymph node metastases (N1+). Future developments may include use of fluorodeoxyglucose-positron emission tomography (FDG-PET) to inform a switch to non-cross resistant chemotherapy pre-operatively and substitution of alternative treatments for chemotherapy in high risk postoperative node positive patients. Conversely, in molecularly selected subgroups such as microsatellite unstable gastroesophageal cancer, peri-operative or adjuvant chemotherapy may not be helpful, and treatments such as immunotherapy may be considered. In this review the most up-to-date clinical trials and translational research in the field of operable gastroesophageal cancer are discussed; with a focus on how best to risk stratify patients with operable disease for peri-operative treatment plus surgery, and how novel therapies might be integrated into standard treatments in order to improve survival outcomes in this patient group.

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Editorial Board



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In This Issue



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Table of Contents



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Masthead



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A Lumbosacral Plexopathy Compressed by Huge Uterine Myoma

imageNo abstract available

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Feasibility and Reliability of Functional Muscle Tests in Lung Transplant Recipients

imageObjective This study investigates the feasibility, reliability, and correlations of recommended functional tests in lung transplant recipients shortly after surgery. Design This is an observational study. Methods Fifty patients (28 females) performed well-standardized maximum isometric back extension in a sitting position, handgrip strength, and Biering-Sørensen endurance tests shortly before discharge from the acute hospital, shortly thereafter, and 2 mos later after subacute rehabilitation. Results Back extension testing was well feasible, but only two thirds of the patients could perform the Biering-Sørensen test at baseline and they experienced a greater number of minor but no major adverse events. Absolute reliability measures and the intraclass correlation coefficients were excellent for the strength (0.97–0.98 [0.95–0.99]) and good for the endurance tests (0.69 [0.26–0.87]). Handgrip revealed high correlation with back strength (≥0.75) but not with Biering-Sørensen scores. Conclusions Well-controlled maximum back strength testing is feasible and reliable, and the scores are highly correlated with grip strength in lung transplant recipients shortly before hospital discharge. The Biering-Sørensen test should be limited to patients without dominant weakness and/or fear. Future research should investigate whether grip instead of back extension strength can safely be used for proper exercise prescription.

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Are Corticosteroid Injections Safe to Inject into Knees With Osteoarthritis?: What Are the Long-term Effects?

No abstract available

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Rehabilitation Outcomes in Spinal Abscess Patients With and Without a History of Intravenous Substance Abuse

imageObjective The aim of the study was to compare functional outcomes of acute inpatient rehabilitation for spinal epidural abscess patients with and without history of intravenous substance abuse. Design This is a retrospective case series study in freestanding rehabilitation hospital. Methods Charts of 28 spinal epidural abscess patients admitted from January 2012 to September 2015: 13 with intravenous substance abuse and 15 without intravenous substance abuse were reviewed. Both groups received standard-of-care rehabilitation. Statistical analyses of Functional Independence Measure scores were conducted using individual 2 (substance use) × 2 (rehabilitation status) repeated measures analysis of variance. Functional outcomes were defined by total Functional Independence Measure scores as well as motor and cognitive subsets. Length of stay and morphine equivalents were also compared. Results There were no significant differences between the two groups. There was a significant main effect of treatment on total Functional Independence Measure scores (P

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Comparing Corticosteroid Preparation and Dose in the Improvement of Shoulder Function and Pain: A Randomized, Single-Blind Pilot Study

imageIntroduction Shoulder pain may arise from inflammation of the bursa separating the supraspinatus tendon from the coracoacromial ligament and acromion. The optimal treatment dose and preparation of intrabursal corticosteroid injection are unknown. Methods This single-blinded equivalence study recruited 62 subjects randomizing them to one of following four arms: methylprednisolone 20 mg, methylprednisolone 40 mg, triamcinolone acetonide 20 mg, or triamcinolone acetonide 40 mg. QuickDASH, subject-reported pain, and adverse events were recorded in time of injection, 3 days later, 3 wks later, and 6 wks later. Primary outcome was QuickDASH improvements 6 wks after injection. Results All four groups were equally matched regarding age, sex, ethnicity, and site injected. Six weeks after injection, no statistically significant changes were noted in QuickDASH improvement (as compared with time of injection) among the four arms. There were no statistically significant differences at 6 wks regarding improvement in pain. There were no statistically significant differences noted in adverse events among the four arms. Conclusions Neither dose nor preparation of injectable corticosteroid influences magnitude of improvement in function or pain experienced. Although this study provides clinically relevant insight regarding corticosteroid dose and type when managing shoulder pain, the modest sample size may limit the conclusions that can be made about efficacy and adverse effects.

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Lean Mass and Functional Recovery in Men With Hip Fracture: A Short-Term Prospective Pilot Study

imageObjective The aim of the study was to assess the capability of different definitions of low appendicular lean mass (aLM) to predict the short-term functional recovery in men with hip fracture. Design We investigated 80 of 95 men with hip fracture admitted consecutively to a rehabilitation hospital. Body composition was assessed by dual-energy x-ray absorptiometry. Functional recovery after inpatient rehabilitation was evaluated using Barthel Index scores. Results The patients with aLM above the cutoff value of 19.75 kg indicated by the Foundation for the National Institutes of Health (FNIH) had significantly higher Barthel Index scores than those with aLM below the cutoff value (P = 0.002). Patients' categorization according to the same threshold (aLM = 19.75 kg) was significantly associated with a Barthel Index score of 85 or higher after adjustment for age, cognitive impairment, hip fracture type, co-morbidities, and medications (odds ratio = 7.17, 95% confidence interval = 1.43–35.94, P = 0.017). Conversely, patients' categorization according to neither Baumgartner's cutoff value (7.26 kg/m2) for aLM/height2 nor Foundation for the National Institutes of Health cutoff value (0.789) for aLM divided by body mass index was significantly associated with the Barthel Index scores. Conclusions Categorization according to the Foundation for the National Institutes of Health threshold for aLM, but not to the Foundation for the National Institutes of Health threshold for aLM/body mass index or Baumgartner's threshold for aLM/height2, was associated with the short-term recovery in activities of daily living after a hip fracture in men.

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Letter to the Editor on “Effects of Antigravity Treadmill Training on Gait, Balance, and Fall Risk in Children With Diplegic Cerebral Palsy”

No abstract available

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Comparison Between Effectiveness of Ultrasound-Guided Corticosteroid Injection Above Versus Below the Median Nerve in Mild to Moderate Carpal Tunnel Syndrome: A Randomized Controlled Trial

imageObjective In this study, the clinical effectiveness of ultrasound-guided corticosteroid injection "above" versus "below" the median nerve for treatment of patients with mild to moderate carpal tunnel syndrome was compared. Design This prospective randomized double-blind clinical trial included 44 patients with mild to moderate carpal tunnel syndrome. The subjects were randomly assigned to two groups to receive ultrasound-guided injection of 40 mg of triamcinolone either "above" or "below" the involved median nerve. Outcome measures were the Boston Carpal Tunnel Questionnaire, visual analog scale, electrophysiological tests, and ultrasonographic measurement of the median nerve cross-sectional area at baseline, 6, and 12 wks after the injection. Results All outcome measures improved significantly in both groups at 6 wks after intervention, and these improvements were persevered up to 12 wks of follow-up (all P values

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Automated Mechanical Peripheral Stimulation Improves Gait Parameters in Subjects With Parkinson Disease and Freezing of Gait: A Randomized Clinical Trial

imageObjective This study aimed to assess spatiotemporal gait parameters and range of motion of lower limbs in subjects with Parkinson disease (PD) and freezing of gait, treated with automated mechanical peripheral stimulation (AMPS) or AMPS SHAM (placebo). Design This randomized clinical trial included 30 subjects allocated into two groups: AMPS (15 subjects with PD) and AMPS SHAM (15 subjects with PD). Fourteen age-matched healthy subjects were also included as a reference group. Both PD groups received the treatment twice a week during 4 weeks. Automated mechanical peripheral stimulation was applied using a commercial medical device (Gondola) and consisted of mechanical pressure in four areas of feet. For AMPS SHAM group, a subliminal stimulus was delivered. Gait analysis were measured before, after the first, after the fourth, and after the eighth sessions. Results We did not find significant differences between AMPS and AMPS SHAM groups either for spatiotemporal gait parameters or for range of motion of lower limbs. However, within-group analysis showed that AMPS group significantly improved spatiotemporal gait parameters and hip rotation range of motion throughout the treatment period. The AMPS SHAM group did not show any improvement. Conclusions Automated mechanical peripheral stimulation therapy induces improvements in spatiotemporal parameters and hip rotation range of motion of subjects with PD and freezing of gait. To Claim CME Credits Complete the self-assessment activity and evaluation online at https://ift.tt/1l80W45 CME Objectives Upon completion of this article, the reader should be able to: (1) Understand the impact of reduced plantar sensitivity on gait in individuals with Parkinson disease; (2) Identify the improvements on spatiotemporal gait parameters in subjects with Parkinson disease and freezing of gait after automated mechanical peripheral stimulation therapy; and (3) Recommend the use of new strategies of plantar stimulus for gait disorders of subjects with Parkinson disease. Level Advanced Accreditation The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

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Effects of Mat Pilates on Physical Functional Performance of Older Adults: A Meta-analysis of Randomized Controlled Trials

imageObjective The present meta-analysis aimed to examine evidence from randomized controlled trials to determine the effects of mat Pilates on measures of physical functional performance in the older population. Design A search was conducted in the MEDLINE/PubMed, Scopus, Scielo, and PEDro databases between February and March 2017. Only randomized controlled trials that were written in English, included subjects aged 60 yrs who used mat Pilates exercises, included a comparison (control) group, and reported performance-based measures of physical function (balance, flexibility, muscle strength, and cardiorespiratory fitness) were included. The methodological quality of the studies was analyzed according to the PEDro scale and the best-evidence synthesis. The meta-analysis was conducted with the Review Manager 5.3 software. Results The search retrieved 518 articles, nine of which fulfilled the inclusion criteria. High methodological quality was found in five of these studies. Meta-analysis indicated a large effect of mat Pilates on dynamic balance (standardized mean difference = 1.10, 95% confidence interval = 0.29–1.90), muscle strength (standardized mean difference = 1.13, 95% confidence interval = 0.30–1.96), flexibility (standardized mean difference = 1.22, 95% confidence interval = 0.39–2.04), and cardiorespiratory fitness (standardized mean difference = 1.48, 95% confidence interval = 0.42–2.54) of elderly subjects. Conclusions There is evidence that mat Pilates improves dynamic balance, lower limb strength, hip and lower back flexibility, and cardiovascular endurance in elderly individuals. Furthermore, high-quality studies are necessary to clarify the effects of mat Pilates on other physical functional measurements among older adults.

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Preliminary Use of the Physical and Neurological Examination of Subtle Signs for Detecting Subtle Motor Signs in Adolescents With Sport-Related Concussion

imageSensitive examination tools are needed to optimize evaluation after sports-related concussion. The Physical and Neurological Examination of Subtle Signs was preliminarily examined for sensitivity to motor changes in a pilot cohort of adolescents aged 13–17 yrs with sports-related concussion. A total of 15 adolescents (5 female adolescents) with sports-related concussion were evaluated up to three times: within 2 wks of injury, approximately 1 mo later (mean, 35 days between visits), and for those not recovered at the second visit, again after clinical recovery (mean, 70 days between the first and last visits for all participants). Comparison data were acquired from 20 age- and sex-matched healthy control athletes with no history of concussion who were evaluated twice (mean, 32 days apart). Main effects of group, time, and interaction effects were evaluated with an analysis of covariance, which controlled for socioeconomic status, times tested, and days between testing sessions. Adolescents with concussion had poorer Physical and Neurological Examination of Subtle Signs performance than controls did at all time points. Performance improved between visits within the concussion group, with no change within the control group. These findings suggest that the Physical and Neurological Examination of Subtle Signs merits additional study in larger cohorts and in combination with other markers of injury to facilitate an enhanced understanding of sports-related concussion and recovery.

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Inability to Perform the Repeated Chair Stand Task Predicts Fall-Related Injury in Older Primary Care Patients

imageObjective The aim of the study was to examine whether the chair stand component of the Short Physical Performance Battery predicts fall-related injury among older adult primary care patients. Design A 2-yr longitudinal cohort study of 430 Boston-area primary care patients aged ≥65 yrs screened to be at risk for mobility decline was conducted. The three components of the Short Physical Performance Battery (balance time, gait speed, and chair stand time) were measured at baseline. Participants reported incidence of fall-related injuries quarterly for 2 yrs. Complementary log-log discrete time hazard models were constructed to examine the hazard of fall-related injury across Short Physical Performance Battery scores, adjusting for age, sex, race, Digit Symbol Substitution Test score, and fall history. Results Participants were 68% female and 83% white, with a mean (SD) age of 76.6 (7.0). A total of 137 (32%) reported a fall-related injury during the follow-up period. Overall, inability to perform the chair stand task was a significant predictor of fall-related injury (hazard ratio = 2.11, 95% confidence interval = 1.23–3.62, P = 0.01). Total Short Physical Performance Battery score, gait component score, and balance component score were not predictive of fall-related injury. Conclusions Inability to perform the repeated chair stand task was associated with increased hazard of an injurious fall for 2 yrs among a cohort of older adult primary care patients.

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Posture-Dependent Dysphagia After Botulinum Toxin Type A Injection at Sternocleidomastoid in a Patient With Athetoid Cerebral Palsy

imageCervical dystonia is a common issue in patients with athetoid cerebral palsy. Botulinum toxin injection to dystonic cervical muscles is a well-recognized treatment option, but it is known to be associated with dysphagia. Previously reported cases of dysphagia after botulinum toxin injection to the sternocleidomastoid muscle were related to the regional spread of toxin to the pharyngeal muscles. We report a unique case of posture-dependent dysphagia due to preactivation of the suprahyoid and infrahyoid muscles to compensate for impaired head stabilization by the weakened sternocleidomastoid muscle while swallowing. This case suggests a possible mechanism of dysphagia in patients with athetoid cerebral palsy.

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Poststroke Headache: An Underdiagnosed Entity?

No abstract available

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Mechanical Traction for Lumbar Radicular Pain: Supine or Prone? A Randomized Controlled Trial

imageObjective The aim of the study was to compare the effects of mechanical lumbar traction either in the supine or in the prone position with conventional physical therapy (PT) in patients with chronic low back pain and lumbosacral nerve root involvement in terms of disability, pain, and mobility. Design Participants (N = 125) were randomly assigned to receive 15 sessions of PT with additional mechanical lumbar traction either in the supine position (supine traction group) or in the prone position (prone traction group) or only PT without traction (PT only group). Patients were assessed at baseline and at the end of the PT sessions in terms of disability, pain, and mobility. Disability was assessed using the modified Oswesty Disability Index; pain was assessed using a visual analog scale, and lumbar mobility was assessed using the modified lumbar Schober test. Results One hundred eighteen patients completed the trial. All groups improved significantly in the Oswesty Disability Index, visual analog scale, and modified lumbar Schober test (P

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Premorbid Activity Limitation Stages Are Associated With Posthospitalization Discharge Disposition

imageObjective Activity of daily living stages and instrumental activity of daily living stage have demonstrated associations with mortality and health service use among older adults. This cohort study aims to assess the associations of premorbid activity limitation stages with acute hospital discharge disposition among community-dwelling older adults. Design Study participants were Medicare beneficiaries aged 65 yrs or older who enrolled in the Medicare Current Beneficiary Survey between 2001 and 2009. Associations of premorbid stages with discharge dispositions were estimated with multinomial logistic regression models adjusted for covariates. Results The proportions of elderly Medicare patients discharged to home with self-care, home with services, postacute care facilities, and other dispositions were 59%, 15%, 19%, and 7%, respectively. The following adjusted relative risk ratios and 95% confidence intervals of postacute care facilities versus home with self-care discharge increased with higher premorbid activity limitation stages (except nonfitting stage III): 1.7 (1.5–2.0), 2.4 (2.0–2.9), 2.4 (1.9–3.0), and 2.5 (1.6–4.1) for activity of daily living stages I–IV; a similar pattern was found for instrumental activity of daily living stages. The adjusted relative risk ratios of discharge to home with services also increased with higher premorbid activity limitation stages compared with no limitation. Conclusions Routinely assessed activity limitation stages predict posthospitalization discharge disposition among older adults and may be used to anticipate postacute care and services use by elderly Medicare beneficiaries.

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Ultrasonography Imaging for the Diagnosis and Guided Injection of Plantaris Tendon Strain in a Patient With Tennis Leg

imageNo abstract available

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Observers in Emergency Medical Settings

Emergency physicians, hospital administrators, and managers often receive requests for outside individuals to be present and observe patient encounters in the emergency department or out-of-hospital care settings. Observers may be members of the institution's health care team or enrolled in the institution's health care professional educational programs, such as those for medical, midlevel provider, paramedic, or other health practitioner students. Because these programs are part of the institution's educational mission, such learners should usually be permitted access as observers.

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Ensuring Emergency Department Patient Access to Appropriate Pain Treatment

The American College of Emergency Physicians (ACEP):

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High Five

The eerie calm was a bit unsettling and disconcerting as the witching hour approached. It was nearing the end of a relatively decent night shift, and the next few moments were critical. Would I be able to sign out a neat and clean department? Or would there be another almost seemingly routine shift change disaster that would sully my plan to escape the night practically unscathed? It was time to tie up loose ends and make disposition decisions that I may have been putting off. Day shift would arrive in an hour, bright eyed and bushy tailed, and soon allow me to retreat from the dawning day and all the new problems that might be associated with it.

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A Woman With Stridor and Respiratory Failure

A 59-year-old woman presented to the emergency department with shortness of breath for 1 day. At presentation, her respiratory rate was 38 breaths/min with expiratory stridor and the use of accessory muscles. Acute upper airway obstruction was immediately diagnosed. Because of imminent respiratory failure, the patient was promptly intubated, with resolution of the respiratory distress symptoms.

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Calendar

Internal Medicine for Primary Care: Derm/Gyn/Neuro/Rheum 4-Day. July 1-4, 2018. Anchorage, AK. Contact: A. Email: abousman@mer.org. Url: www.mer.org. (16.0)

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Classified 2018 Advertising Rates & Information

Ads and complete payments must be received in writing by the issue's deadline date. These deadlines apply to insertions, cancellations, and changes.

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In reply:

I thank Dr. Niforatos for his interest in our study. He indicates that we performed a cost-effectiveness analysis of freestanding emergency departments (EDs), which we did not. Cost-effectiveness evaluations require measures of the costs of care relative to their net health benefits.1 Our study documented that the net costs of freestanding EDs are substantially higher than those for urgent care centers for the many diagnoses and procedures that are commonly observed at both locations.2

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Young Man With Wrist Pain

A 35-year-old man presented to the emergency department with acute-on-chronic left wrist pain for a month. The patient tolerated the pain until 2 days ago, when he experienced a mechanical fall from standing, in which he landed on his left outstretched hand. His social history included employment as a construction worker. Physical examination was remarkable only for tenderness over the left lunate bone. Radiographs of the left wrist were ordered.

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How Will Our Research Affect Our Patients?

The editorial decision1 to publish the letter from Dr. Ho et al2 with various allegations and rebuttals is a unique educational opportunity. In the December issue of Annals, a lively debate between numerous authors provided stimulating methodological critiques, salient reminders of conflicts of interest, and issues that arise with use of commercial data. This debate is ultimately responding to the authors' thematic conclusion—despite the need for further research—that "freestanding EDs [emergency departments] potentially waste societal resources because they represent a high-cost provider for services that could be delivered in lower-cost settings."2

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Woman With Hand Pain and Swelling

A 37-year-old woman with no medical history presented with 4 days of atraumatic pain, erythema, and swelling overlying the palmar aspect of her left small-finger metacarpal-phalangeal joint (Figure 1). Range of motion of the metacarpal-phalangeal joint was severely limited by pain. This had worsened despite 48 hours of antibiotic treatment. Her vital signs were normal. White blood cell count was 10.8×103/μL. C-reactive protein level was elevated, at 16.4 mg/L. Ultrasonography showed a metacarpal-phalangeal joint effusion and calcification (Figure 2).

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In reply:

I appreciate the kind remarks of Dr. Niforatos and thank him for further identifying needed research not yet done, but crucial to answering the question of how best to provide care for these patients. I hope someone has the persistence and logistics to complete such a study, and that in the meantime the US public continues to expect, and receive, treatment consistent with the prudent layperson standard. This is a good example of a societal problem that is not likely to be solved by limited and self-interested research by parties responsible for (and benefitting from) only certain aspects of the solution.

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A Woman With a Click in Her Throat

A 26-year-old woman presented to the emergency department with 1 year of generalized headaches, sinus drainage, and a clicking sensation in her posterior pharynx. She had attempted over-the-counter antihistamines and had been receiving several antibiotics, without relief. She was concerned by the daily clicking in her pharynx, which had gradually worsened. On examination, the only positive physical examination finding was a rhythmic contraction of her entire palate that resulted in occasional audible clicks (Figures 1 and 2; Video E1, available online at https://ift.tt/P50aok).

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Basics of Emergency Medicine: Pediatrics, 2nd Edition

Comfort in caring for pediatric patients can vary greatly, depending on how frequently you treat them. Even common complaints such as fever are nuanced, the evaluation varying greatly by age. There's a delicate balance in investigating that which is truly concerning and reducing the real risks of overtesting. For those new to pediatric emergency medicine (medical students, interns, and rotating residents) or those who treat pediatric patients less frequently, EMRA's Basics of Emergency Medicine: Pediatrics is a great resource.

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Recognition of Subtle ECG Manifestations of Left Anterior Descending Coronary Artery Occlusion

Hamade et al1 describe a case of a young man with myocardial infarction caused by occlusion of the left anterior descending coronary artery. The first recorded ECG is described as being "without ischemic changes." We suggest, however, that one must consider this ECG as manifesting left anterior descending occlusion until and unless proven otherwise. Left anterior descending occlusion is known to often present with less than 1 mm of ST-segment elevation in the anterior leads2; here, it is approximately 1 mm at the J point relative to the PQ junction.

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Basics of Emergency Medicine, 3rd Edition

While reading the introduction of Basics of Emergency Medicine, we were immediately transported back to the time when we were interns. Like most new physicians, we were full of didactic knowledge but lacking in clinical experience; this often resulted in incomplete evaluations and disorganized thoughts. With a tracking board full of various chief complaints and little understanding on how to approach them, we found that this book would have been exactly what we needed.

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Adult Male With Scrotal Swelling and Pain

A previously healthy 36-year-old man presented to the emergency department for a 1-week history of progressive scrotal swelling and pain. He also endorsed 2 weeks of abdominal discomfort and vomiting. On examination, the patient had a temperature of 100.1°F (37.8°C), pulse rate of 93 beats/min, blood pressure of 131/76 mm Hg, swollen erythematous right hemiscrotum without crepitus, and suprapubic tenderness. Laboratory results were notable for a WBC count of 33.3 (103/μL). Scrotal ultrasonography (Figure 1) showed a right-sided complex fluid collection with internal septations.

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Discrepancy Between Clinician Gestalt and Subjective Component of the Wells Score in the Evaluation of Pulmonary Embolism

Schriger et al1 recently showed that studies rarely compare decision aids with physician judgment. In the evaluation of pulmonary embolism, clinicians may use either their subjective clinical judgment (ie, gestalt) or a decision aid (eg, Wells score) to determine the pretest probability of pulmonary embolism. Research shows that the Wells score and clinical gestalt are similarly accurate.2,3 Research also suggests that most of the predictive power of the Wells score lies in its subjective question, "Are alternative diagnoses less likely than pulmonary embolism?"4 However, the degree to which the subjective component of the Wells score and clinician gestalt are correlated is not known.

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Young Woman With a Sore Throat and Neck Mass

A 30-year-old woman presented with neck redness and a sore throat for 4 days. She had a multiple-year history of recurrent swelling to the anterior part of her neck. She had been recently treated for sinusitis with amoxicillin 1 week before presentation. She reported dysphagia and odynophagia. On examination, she had midline anterior neck tenderness around the thyroid cartilage. A computed tomography (CT) soft tissue neck image was obtained (Figures 1 and 2).

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In reply:

We thank Dr. Akhter et al1 for their thoughtful comments in regard to our recent article and for sharing review of their data about the pulmonary embolism rule-out criteria. Their data confirm what many studies have shown before: that clinician gestalt often equals or outperforms clinical decision aids.

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HIPAA

I can't write about the specifics so instead I just carry them around with me like shards of glass in the sea. I roll them back and forth and back and forth till the edges wear down and the shine turns to glaze and still they are heavy and jangling. In the morning I wake to find them strewn on the sands of my mind, blue and green and white, imperfect triangles and rectangles and shapes whose names lie long forgotten in some elementary school classroom where I dreamed of being a doctor.

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TP53, STK11 and EGFR Mutations Predict Tumor Immune Profile and the Response to anti-PD-1 in Lung Adenocarcinoma

Purpose: By unlocking anti-tumor immunity, antibodies targeting programmed cell death 1 (PD-1) exhibit impressive clinical results in non-small cell lung cancer, underlining the strong interactions between tumor and immune cells. However, factors that can robustly predict long-lasting responses are still needed. Experimental Design: We performed in depth immune profiling of lung adenocarcinoma using an integrative analysis based on immunohistochemistry, flow-cytometry and transcriptomic data. Tumor mutational status was investigated using next-generation sequencing. The response to PD-1 blockers was analyzed from a prospective cohort according to tumor mutational profiles and to PD-L1 expression, and a public clinical database was used to validate the results obtained. Results: We showed that distinct combinations of STK11, EGFR and TP53 mutations, were major determinants of the tumor immune profile (TIP) and of the expression of PD-L1 by malignant cells. Indeed, the presence of TP53 mutations without co-occurring STK11 or EGFR alterations (TP53-mut/STK11-EGFR-WT), independently of KRAS mutations, identified the group of tumors with the highest CD8 T cell density and PD-L1 expression. In this tumor subtype, pathways related to T cell chemotaxis, immune cell cytotoxicity, and antigen processing were up-regulated. Finally, a prolonged progression-free survival (PFS: HR=0.32; 95% CI, 0.16-0.63, p<0.001) was observed in anti-PD-1 treated patients harboring TP53-mut/STK11-EGFR-WT tumors. This clinical benefit was even more remarkable in patients with associated strong PD-L1 expression. Conclusions: Our study reveals that different combinations of TP53, EGFR and STK11 mutations, together with PD-L1 expression by tumor cells, represent robust parameters to identify best responders to PD-1 blockade.



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Magnetic Resonance Imaging of Tumor Associated Macrophages: Clinical Translation

Purpose: Tumor associated macrophages (TAM) in malignant tumors have been linked to tumor aggressiveness and represent a new target for cancer immunotherapy. As new TAM-targeted immunotherapies are entering clinical trials, it is important to detect and quantify TAM with non-invasive imaging techniques. The purpose of this study was to determine if ferumoxytol-enhanced MRI can detect TAM in lymphomas and bone sarcomas of pediatric patients and young adults. Experimental Design: In a first-in-patient, IRB-approved prospective clinical trial, 25 pediatric and young adult patients with lymphoma or bone sarcoma underwent ferumoxytol-enhanced MRI. To confirm ferumoxytol enhancement, five pilot patients (2 lymphoma, 3 bone sarcoma) underwent pre- and post-contrast MRI. Subsequently, 20 patients (10 lymphoma, 10 bone sarcoma) underwent ferumoxytol-enhanced MRI 24-48 hours after intravenous injection, followed by tumor biopsy/resection and macrophage staining. To determine if ferumoxytol-MRI can differentiate tumors with different TAM content, we compared T2* relaxation times of lymphomas and bone sarcomas. Tumor T2* values of 20 patients were correlated with CD68+ and CD163+ TAM quantities on histopathology. Results: Significant ferumoxytol tumor enhancement was noted on post-contrast scans compared to pre-contrast scans (P = 0.036). Bone sarcomas and lymphomas demonstrated significantly different MRI enhancement and TAM density (P < 0.05). Within each tumor group, T2* signal enhancement on MR images correlated significantly with the density of CD68+ and CD163+ TAM (P < 0.05). Conclusions: Ferumoxytol-enhanced MRI is immediately clinically applicable and could be used to stratify patients with TAM-rich tumors to immune-targeted therapies and to monitor tumor response to these therapies.



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Phase I Study of CC-486 Alone and in Combination With Carboplatin or nab-paclitaxel in Patients With Relapsed or Refractory Solid Tumors

Purpose: This large two-part, three-arm phase I study examined the safety and tolerability of CC-486 (an oral formulation of azacitidine, a hypomethylating agent) alone or in combination with the cytotoxic agents, carboplatin or nab-paclitaxel, in patients with advanced unresectable solid tumors. Patients and Methods: Part 1 (n=57) was a dose escalation of CC-486 alone (arm C) or with carboplatin (arm A) or nab-paclitaxel (arm B). The primary endpoint was safety, maximum tolerated dose, and recommended part 2 dose (RP2D) of CC-486. In part 2 (n=112), the primary endpoint was the safety and tolerability of CC-486 administered at the RP2D for each treatment arm, in tumor-specific expansion cohorts. Secondary endpoints included pharmacokinetics, pharmacodynamics, and antitumor activity of CC-486. Results: At pharmacologically active doses CC-486 in combination with carboplatin or nab-paclitaxel had a tolerable safety profile and no drug-drug interactions. The CC-486 RP2D was determined as 300 mg (once daily, days 1-14/21) in combination with carboplatin (arm A) or as monotherapy (arm C); and 200 mg in the same dosing regimen in combination with nab-paclitaxel (arm B). Albeit limited by the small sample size, CC-486 monotherapy resulted in partial responses (three/eight) and stable disease (four/eight) in patients with nasopharyngeal cancer. Three of the stable disease responses lasted more than 150 days. Conclusion: CC-486 is well tolerated alone or in combination with carboplatin or nab-paclitaxel. Exploratory analyses suggest clinical activity of CC-486 monotherapy in nasopharyngeal cancer and provided the basis for an ongoing phase II clinical trial (ClinicalTrials.gov identifier: NCT02269943).



https://ift.tt/2IlOxdh

Combined HDAC and Bromodomain Protein Inhibition Reprograms Tumor Cell Metabolism and elicits Synthetic Lethality in Glioblastoma

Purpose: Glioblastoma remain a challenge in oncology in part due to tumor heterogeneity. Experimental Design: Patient-derived xenograft and stem-like glioblastoma cells were used as the primary model systems. Results: Based on a transcriptome and subsequent gene set enrichment analysis (GSEA), we show by using clinically validated compounds that combined histone deacetylase (HDAC) inhibition and Bromodomain protein (BRD) inhibition results in pronounced synergistic reduction in cellular viability in patient-derived xenograft and stem-like glioblastoma cells.  Transcriptome based GSEA analysis suggests that metabolic reprogramming is involved with synergistic reduction of oxidative and glycolytic pathways in the combination treatment. Extracellular flux analysis confirms that combined HDAC inhibition and BRD inhibition blunts oxidative and glycolytic metabolism of cancer cells, leading to a depletion of intracellular ATP production and total ATP levels. In turn, energy deprivation drives an integrated stress response, originating from the endoplasmic reticulum. This results in an increase in pro-apoptotic Noxa. Aside from Noxa, we encounter a compensatory increase of anti-apoptotic Mcl-1 protein. Pharmacological, utilizing the FDA-approved drug sorafenib, and genetic inhibition of Mcl-1 enhanced the effects of the combination therapy. Finally, we show in orthotopic patient-derived xenografts of GBM, that the combination treatment reduces tumor growth, and that the triple therapy, involving clinically validated compounds, panobinostat, OTX015 and sorafenib further enhances these effects, culminating in a significant regression of tumors in vivo. Conclusion: Overall, these results warrant clinical testing of this novel, efficacious combination therapy.



https://ift.tt/2KsbKqI

Preclinical Antitumor Activity of a Novel Anti-c-KIT Antibody Drug Conjugate against Mutant and Wild Type c-KIT Positive Solid Tumors

Purpose: c-KIT overexpression is well-recognized in cancers such as GIST, SCLC, melanoma, NSCLC and AML. Treatment with the small molecule inhibitors imatinib, sunitinib and regorafenib result in resistance (c-KIT mutant tumors) or limited activity (c-KIT wildtype tumors). We selected an anti-c-KIT ADC approach to evaluate the anti-cancer activity in multiple disease models. Experimental Design: A humanized anti-c-KIT antibody LMJ729 was conjugated to the microtubule destabilizing maytansinoid, DM1, via a non-cleavable linker (SMCC). The activity of the resulting ADC, LOP628, was evaluated in vitro against GIST, SCLC and AML models and in vivo against GIST and SCLC models. Results: LOP628 exhibited potent anti-proliferative activity on c-KIT positive cell lines whereas LMJ729 displayed little to no effect. At exposures predicted to be clinically achievable, LOP628 demonstrated single administration regressions or stasis in GIST and SCLC xenograft models in mice. LOP628 also displayed superior efficacy in an imatinib-resistant GIST model. Further, LOP628 was well-tolerated in monkeys with an adequate therapeutic index several fold above efficacious exposures. Safety findings were consistent with the pharmacodynamic effect of neutropenia due to c-KIT-directed targeting. Additional toxicities were considered off-target and were consistent with DM1, such as effects in the liver and hematopoietic/lymphatic system. Conclusions:The preclinical findings suggest that the c-KIT directed ADC may be a promising therapeutic for the treatment of mutant and wildtype c-KIT positive cancers and supported the clinical evaluation of LOP628 in GIST, AML and SCLC patients.



https://ift.tt/2IoMEww

HP1{gamma} promotes lung adenocarcinoma by downregulating the transcription-repressive regulators NCOR2 and ZBTB7A

Lung adenocarcinoma (LUAD) is a major form of lung cancer, which is the leading cause of cancer death. Histone methylation reader proteins mediate the effect of histone methylation, a hallmark of epigenetic and transcriptional regulation of gene expression. However, their roles in LUAD are poorly understood. Here our bioinformatic screening and analysis in search of an LUAD-promoting histone methylation reader protein show that heterochromatin protein 1γ (HP1γ; also called CBX3) is among the most frequently overexpressed and amplified histone reader proteins in human LUAD, and that high HP1γ mRNA levels are associated with poor prognosis in LUAD patients. In vivo depletion of HP1γ reduced K-RasG12D-driven LUAD and lengthened survival of mice bearing K-RasG12D-induced LUAD. HP1γ and its binding activity to methylated histone H3 lysine 9 were required for the proliferation, colony formation, and migration of LUAD cells. HP1γ directly repressed expression of the transcription-repressive regulators NCOR2 and ZBTB7A. Knockdown of NCOR2 or ZBTB7A significantly restored defects in proliferation, colony formation, and migration in HP1γ-depleted LUAD cells. Low NCOR2 or ZBTB7A mRNA levels were associated with poor prognosis in LUAD patients and correlated with high HP1γ mRNA levels in LUAD samples. NCOR2 and ZBTB7A downregulated expression of tumor-promoting factors such as ELK1 and AXL, respectively. These findings highlight the importance of HP1γ and its reader activity in LUAD tumorigenesis and reveal a unique LUAD-promoting mechanism in which HP1γ downregulates NCOR2 and ZBTB7A to enhance expression of pro-tumorigenic genes.

https://ift.tt/2GjXFZP

Extracorporeal Photochemotherapy Drives Monocyte-to-Dendritic Cell Maturation to Induce Anti-Cancer Immunity

Extracorporeal photochemotherapy (ECP) is a cancer immunotherapy for cutaneous T cell lymphoma (CTCL) operative in more than 350 centers worldwide. While its efficacy and favorable safety profile have driven its widespread use, elucidation of its underlying mechanism has been difficult. In this study, we identify the principal contributors to the anti-cancer immunotherapeutic effects of ECP, with the goal of enhancing potency and broadening applicability to additional malignancies. First, we scaled down the clinical ECP leukocyte-processing device to mouse size. Second, we used that miniaturized device to produce a cellular vaccine that regularly initiated therapeutic anti-melanoma immunity. Third, we individually subtracted key factors from either the immunizing inoculum or the treated animal to ascertain their contribution to the in vivo anti-melanoma response. Platelet-signaled monocyte-to-dendritic cell (DC) differentiation followed by sorting/processing/presentation of tumor antigens derived from internalized apoptotic tumor cells were absolute requirements. As in clinical ECP, immunogenic cell death of tumor cells was finely titrated by DNA cross-linkage mediated by photoactivated 8-methoxypsoralen (8-MOPA). ECP-induced tumor-loaded DC were effective immunotherapeutic agents only if they were spared exposure to 8-MOPA, indicating that healthy DC are required for ECP. Infusion of responder T cells into naïve tumor-challenged mice established the protective role of stimulated T cell anti-tumor immunity. Collectively, these results reveal that selective anti-tumor effects of ECP are initiated by tumor antigen-loaded, ECP-induced DC, which promote potent collaboration between CD4 and CD8 tumor-specific T cells. These mechanistic insights suggest potential therapeutic applicability of ECP to solid tumors in addition to CTCL.

https://ift.tt/2L1lERc

Targeting the Hsp40/Hsp70 chaperone axis as a novel strategy to treat castration-resistant prostate cancer

Castration-resistant prostate cancer (CRPC) is characterized by reactivation of androgen receptor (AR) signaling in part by elevated expression of AR splice variants (ARv) including ARv7, a constitutively active, ligand binding domain (LBD)-deficient variant whose expression has been correlated with therapeutic resistance and poor prognosis. In a screen to identify small molecule dual inhibitors of both androgen-dependent and androgen-independent AR gene signatures, we identified the chalcone C86. Binding studies using purified proteins and CRPC cell lysates revealed C86 to interact with heat shock protein 40 (Hsp40). Pulldown studies using biotinylated-C86 found Hsp40 present in a multi-protein complex with full-length (FL-) AR, ARv7 and Hsp70 in CRPC cells. Treatment of CRPC cells with C86 or the allosteric heat shock protein 70 (Hsp70) inhibitor JG98 resulted in rapid protein destabilization of both FL-AR and ARv, including ARv7, concomitant with reduced FL-AR- and ARv7-mediated transcriptional activity. The glucocorticoid receptor (GR), whose elevated expression in a subset of CRPC also leads to androgen-independent AR target gene transcription, was also destabilized by inhibition of Hsp40 or Hsp70. In vivo, Hsp40 or Hsp70 inhibition demonstrated single agent and combinatorial activity in a 22Rv1 CRPC xenograft model. These data reveal that, in addition to recognized roles of Hsp40 and Hsp70 in FL-AR LBD remodeling, ARv lacking the LBD remain dependent on molecular chaperones for stability and function. Our findings highlight the feasibility and potential benefit of targeting the Hsp40/Hsp70 chaperone axis to treat prostate cancer that has become resistant to standard anti-androgen therapy.

https://ift.tt/2GkVBkx

Genome-Wide Search for Quantitative Trait Loci Controlling Important Plant and Flower Traits in Petunia Using an Interspecific Recombinant Inbred Population of Petunia axillaris and Petunia exserta

A major bottleneck in plant breeding has been the much limited genetic base and much reduced genetic diversity in domesticated, cultivated germplasm. Identification and utilization of favorable gene loci or alleles from wild or progenitor species can serve as an effective approach to increasing genetic diversity and breaking this bottleneck in plant breeding. This study was conducted to identify quantitative trait loci (QTL) in wild or progenitor petunia species that can be used to improve important horticultural traits in garden petunia. An F7 recombinant inbred population derived between Petunia axillaris and P. exserta was phenotyped for plant height, plant spread, plant size, flower counts, flower diameter, flower length, and days to anthesis, in Florida in two consecutive years. Transgressive segregation was observed for all seven traits in both years. The broad-sense heritability estimates for the traits ranged from 0.20 (days to anthesis) to 0.62 (flower length). A genome-wide genetic linkage map consisting 368 single nucleotide polymorphism bins and extending over 277 cM was searched to identify QTL for these traits. Nineteen QTL were identified and localized to five linkage groups. Eleven of the loci were identified consistently in both years; several loci explained up to 34.0% and 24.1% of the phenotypic variance for flower length and flower diameter, respectively. Multiple loci controlling different traits are co-localized in four intervals in four linkage groups. These intervals contain desirable alleles that can be introgressed into commercial petunia germplasm to expand the genetic base and improve plant performance and flower characteristics in petunia.



https://ift.tt/2k407LD

A Genomic Region Containing REC8 and RNF212B Is Associated with Individual Recombination Rate Variation in a Wild Population of Red Deer (Cervus elaphus)

Recombination is a fundamental feature of sexual reproduction, ensuring proper disjunction, preventing mutation accumulation and generating new allelic combinations upon which selection can act. However it is also mutagenic, and breaks up favourable allelic combinations previously built up by selection. Identifying the genetic drivers of recombination rate variation is a key step in understanding the causes and consequences of this variation, how loci associated with recombination are evolving and how they affect the potential of a population to respond to selection. However, to date, few studies have examined the genetic architecture of recombination rate variation in natural populations. Here, we use pedigree data from ~2,600 individuals genotyped at ~38,000 SNPs to investigate the genetic architecture of individual autosomal recombination rate in a wild population of red deer (Cervus elaphus). Female red deer exhibited a higher mean and phenotypic variance in autosomal crossover counts (ACC). Animal models fitting genomic relatedness matrices showed that ACC was heritable in females (h2 = 0.12) but not in males. A regional heritability mapping approach showed that almost all heritable variation in female ACC was explained by a genomic region on deer linkage group 12 containing the candidate loci REC8 and RNF212B, with an additional region on linkage group 32 containing TOP2B approaching genome-wide significance. The REC8/RNF212B region and its paralogue RNF212 have been associated with recombination in cattle, mice, humans and sheep. Our findings suggest that mammalian recombination rates have a relatively conserved genetic architecture in both domesticated and wild systems, and provide a foundation for understanding the association between recombination loci and individual fitness within this population.



https://ift.tt/2KqiNQC

A Targeted RNAi Screen Reveals Drosophila Female-Sterile Genes That Control the Size of Germline Stem Cell Niche During Development

Adult stem cells maintain tissue homeostasis. This unique capability largely depends on the stem cell niche, a specialized microenvironment, which preserves stem cell identity through physical contacts and secreted factors. In many cancers, latent tumor cell niches are thought to house stem cells and aid tumor initiation. However, in developing tissue and cancer it is unclear how the niche is established. The well-characterized germline stem cells (GSCs) and niches in the Drosophila melanogaster ovary provide an excellent model to address this fundamental issue. As such, we conducted a small-scale RNAi screen of 560 individually expressed UAS-RNAi lines with targets implicated in female fertility. RNAi was expressed in the soma of larval gonads, and screening for reduced egg production and abnormal ovarian morphology was performed in adults. Twenty candidates that affect ovarian development were identified and subsequently knocked down in the soma only during niche formation. Feminization factors (Transformer, Sex lethal, and Virilizer), a histone methyltransferase (Enhancer of Zeste), a transcriptional machinery component (Enhancer of yellow 1), a chromatin remodeling complex member (Enhancer of yellow 3) and a chromosome passenger complex constituent (Incenp) were identified as potentially functioning in the control of niche size. The identification of these molecules highlights specific molecular events that are critical for niche formation and will provide a basis for future studies to fully understand the mechanisms of GSC recruitment and maintenance.



https://ift.tt/2IJkCeo

FDA Approves 'Biosimilar' Drug to Treat Certain Types of Anemia

TUESDAY, May 15, 2018 -- Retacrit (epoetin alfa-epbx) has been approved by the U.S. Food and Drug Administration as the first "biosimilar" to the anemia drugs Epogen and Procrit. Epogen and Procrit are approved to treat anemia caused by chronic...

https://ift.tt/2IosK0u

Prescription Med Use in Children Down Overall From 1999 to 2014

TUESDAY, May 15, 2018 -- From 1999 to 2014 there was a decrease in prescription medication use overall among children and adolescents, according to a study published in the May 15 issue of the Journal of the American Medical Association. Craig M....

https://ift.tt/2IL9Wf8

Acupuncture Doesn't Up Live Birth Rate for Women Having IVF

TUESDAY, May 15, 2018 -- For women undergoing in vitro fertilization (IVF), acupuncture at the time of ovarian stimulation and embryo transfer is not associated with a significant difference in live birth rate compared with sham acupuncture,...

https://ift.tt/2InpqTa

Prevalence of Adult E-Cigarette Use Up from 2014 to 2016

TUESDAY, May 15, 2018 -- The prevalence of electronic cigarette (e-cigarette) ever use increased among U.S. adults from 2014 to 2016, according to a research letter published in the May 15 issue of the Journal of the American Medical...

https://ift.tt/2k0P8T6

Dual-Hormone System May Lower Time in Hypoglycemia in T1DM

TUESDAY, May 15, 2018 -- For physically active adults with type 1 diabetes, the addition of glucagon delivery to a closed-loop system using wearable sensors with automated exercise detection is associated with reduced hypoglycemia, according to a...

https://ift.tt/2Iosyyi

Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2)

Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2)

Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2), Published online: 16 May 2018; doi:10.1038/s41416-018-0087-9

Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2)

https://ift.tt/2Imn3UI

A Gradient-Based Approach for Breast DCE-MRI Analysis

Breast cancer is the main cause of female malignancy worldwide. Effective early detection by imaging studies remains critical to decrease mortality rates, particularly in women at high risk for developing breast cancer. Breast Magnetic Resonance Imaging (MRI) is a common diagnostic tool in the management of breast diseases, especially for high-risk women. However, during this examination, both normal and abnormal breast tissues enhance after contrast material administration. Specifically, the normal breast tissue enhancement is known as background parenchymal enhancement: it may represent breast activity and depends on several factors, varying in degree and distribution in different patients as well as in the same patient over time. While a light degree of normal breast tissue enhancement generally causes no interpretative difficulties, a higher degree may cause difficulty to detect and classify breast lesions at Magnetic Resonance Imaging even for experienced radiologists. In this work, we intend to investigate the exploitation of some statistical measurements to automatically characterize the enhancement trend of the whole breast area in both normal and abnormal tissues independently from the presence of a background parenchymal enhancement thus to provide a diagnostic support tool for radiologists in the MRI analysis.

https://ift.tt/2rIRR7E

The Utility of Next-Generation Sequencing for Primary Immunodeficiency Disorders: Experience from a Clinical Diagnostic Laboratory

Introduction. Primary immune deficiency disorders (PIDs) are a group of diseases with profound defects in immune cells. The traditional diagnostics have evolved from clinical evaluation, flow cytometry, western blotting, and Sanger sequencing to focusing on small groups of genes. However, this is not sufficient to confirm the suspicion of certain PIDs. Our innovative approach to diagnostics outlines the algorithm for PIDs and the clinical utility of immunophenotyping with a custom-designed multigene panel. Materials and Methods. We have designed a diagnostic algorithm based on flow cytometry studies to classify the patients; then the selected multigene panel was sequenced. In silico analysis for mutations was carried out using SIFT, Polyphen-2, and MutationTaster. Results and Discussion. The causative mutation was identified in 46% of PIDs. Based on these results, this new algorithm including immune phenotyping and NGS for PIDs was suggested for the clinical use. Conclusions. This study provides a thorough validation of diagnostic algorithm and indicates that still the traditional methods can be used to collect significant information related to design of most current diagnostics. The benefits of such testing are for diagnosis and prevention including the prenatal and preimplantation diagnosis, prognosis, treatment, and research.

https://ift.tt/2L3IN5z

A Review on Adducin from Functional to Pathological Mechanisms: Future Direction in Cancer

Adducin (ADD) is a family of membrane skeleton proteins including ADD1, ADD2, and ADD3 that are encoded by distinct genes on different chromosomes. Adducin is primarily responsible for the assembly of spectrin-actin network that provides physical support to the plasma membrane and mediates signal transduction in various cellular physiological processes upon regulation by protein kinase C-dependent and calcium/calmodulin-dependent pathways. Abnormal phosphorylation, genetic variations, and alternative splicing of adducin may contribute to alterations in cellular functions involved in pathogenic processes. These alterations are associated with a wide range of diseases including cancer. This paper begins with a discussion on how adducin partakes in the structural formation of membrane skeleton, its regulation, and related functional characteristics, followed by a review on the pathogenesis of hypertension, biliary atresia, and cancer with respect to increased disease susceptibility mediated by adducin polymorphism and/or dysregulation. Given the functional diversity of adducin in different cellular compartments, we aim to provide a knowledge base whereby its pathophysiological roles can be better understood. More importantly, we aim to provide novel insights that may be of significance in turning the adducin model to clinical application.

https://ift.tt/2GjD488

Ecotoxicological and Interactive Effects of Copper and Chromium on Physiochemical, Ultrastructural, and Molecular Profiling in Brassica napus L.

Heavy metal accumulation causes huge environmental problems, particularly in agricultural ecosystems which have deteriorative effects on the yield and quality of crops. Individual copper (Cu) and chromium (Cr) effects have been investigated extensively in plants; however, co-contamination of Cu and Cr induced stress on Brassica napus L. is still unclear. In the present experiment, the interactive effects of Cu and Cr were studied in two B. napus cultivars (Zheda 622 and ZS 758). Results showed that the application of Cr was more toxic than Cu, and their combined stress had shown a significant adverse effect on plant growth. Biomass and photosynthetic pigment were decreased remarkably under all metal treatments. Individual treatments of Cu and Cr and their combination cause the accumulation of ROS and lipid peroxidation. Moreover, the activities of antioxidant enzymes and their mRNA transcription levels, such as catalase (CAT), ascorbate peroxidase, glutathione reductase, superoxide dismutase, and peroxidase, were increased, especially when treated with Cr alone or under Cu+Cr combined treatment in both cultivars, except for the CAT activity which was decreased in both leaves and roots of sensitive cultivar Zheda 622 as compared with their respective controls. Additionally, nonenzymatic antioxidants like reduced and oxidized glutathione showed a differential activity pattern in roots and leaves of both cultivars. A more pronounced modification in chloroplast ultrastructure was observed in both cultivars under Cu+Cr treatment followed by Cr and Cu alone treatments. Furthermore, synergistic effects of Cu and Cr were prominent; this may be due to the enhanced metals uptake under combined treatment, which suggests that Cr and Cu interaction is not competitive but is rather additive and genotypic-dependent.

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Factors influencing reoperation following breast‐conserving surgery

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2k0EsUc

Bone graft in posterior spine fusion for adolescent idiopathic scoliosis: a meta‐analysis

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2wHLsPb

Rare case of pilomatrixoma of the lower eyelid following blunt trauma

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2IJA61K

Rare cases of hidradenitis suppurativa (Verneuil's disease) of perineum and perianal region

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2wGOwuM

Laparoscopic versus open approach to neurolytic celiac plexus block in inoperable pancreatic cancer

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2jZIWdN

First-time mothers’ birth beliefs, preferences, and actual birth: A longitudinal observational study

Publication date: Available online 9 May 2018
Source:Women and Birth
Author(s): Heidi Preis, Michal Eisner, Rony Chen, Yael Benyamini
ProblemBirth preferences, such as mode and place of birth and other birth options, have important individual and societal implications, yet few studies have investigated the mechanism which predicts a wide range of childbirth options simultaneously.BackgroundBasic beliefs about birth as a natural and as a medical process are both predictive factors for childbirth preferences. Studies investigating birth beliefs, preferences, and actual birth are rare.AimTo test a predictive model of how these beliefs translate into birth preferences and into actual birth related-options.MethodsLongitudinal observational study including 342 first-time expectant mothers recruited at women's health centres and natural birth communities in Israel. All women filled out questionnaires including basic birth beliefs and preferred birth options. Two months postpartum, they filled out a questionnaire including detailed questions regarding actual birth.FindingsStronger beliefs about birth being natural were related to preferring a more natural place and mode of birth and preferring more natural birth-related options. Stronger beliefs about birth being medical were associated with opposite options. The preferences mediated the association between the birth beliefs and actual birth. The beliefs predicted the preferences better than they predicted actual birth.DiscussionBirth beliefs are pivotal in the decision-making process regarding preferred and actual birth options. In a medicalized obstetric system, where natural birth is something women need to actively seek out and insist on, the predictive powers of beliefs and of preferences decrease.ConclusionWomen's beliefs should be recognized and birth preferences respected.



https://ift.tt/2rL7IBX

Mindfulness-based programme on the psychological health of pregnant women

Publication date: Available online 8 May 2018
Source:Women and Birth
Author(s): Wan-Lin Pan, Meei-Ling Gau, Tzu-Ying Lee, Hei-Jen Jou, Chieh-Yu Liu, Tzung-Kuen Wen
ProblemPreparation of psychological well-being is an important component of antenatal education for childbirth, but few courses focus on this component.BackgroundThe psychosocial health of pregnant women is known to affect perinatal outcomes. Psychosocial stress in women has been associated with increased obstetric interventions and has been shown to affect the health of both mother and child.AimTo explore the efficacy of an eight-week Mindfulness-Based Childbirth and Parenting programme on reducing prenatal stress, depression, mindfulness, and childbirth self-efficacy.MethodsIn this prospective and randomized controlled trial study, 104 women between 13 and 28 weeks gestation were enrolled and assigned randomly into two groups. Participants in the experimental group received mindfulness-based programme and practice-at-home with audio recordings. The comparison group received traditional education classes. Psychological health was assessed at baseline, post-intervention, and 36-week gestation.FindingsSignificant differences were seen in both groups in terms of changes over time in stress, depression, childbirth self-efficacy, and mindfulness, as compared with baseline. In gestation week 36, stress scores were slightly higher and childbirth self-efficacy and mindfulness scores were lower for both groups, but all scores were relatively better in the experimental than in the comparison group.ConclusionsPerinatal mental health problems affect mothers, their infants, and society. The eight-week mindfulness programme effectively reduced self-perceived stress and depression and increased childbirth self-efficacy and mindfulness. Future research is needed to explore the potential benefits, mechanisms, and effects on maternal and infant birth outcomes of mindfulness.



https://ift.tt/2L1Fbkq

Re-examining pregnancy-related anxiety: A replication study

Publication date: Available online 7 May 2018
Source:Women and Birth
Author(s): Robyn Brunton, Rachel Dryer, Anthony Saliba, Jane Kohlhoff
BackgroundRecognition of pregnancy-related anxiety as a distinct anxiety is supported by evidence differentiating it from general anxiety and depression. Adverse associations with pregnancy-related anxiety further support this distinction. An influential study by Huizink et al. (2004), demonstrated that anxiety and depression contribute little to the variance of pregnancy-related anxiety, yet this study has not been replicated. Further, addressing limitations of the original study will provide further clarity to the findings.MethodsParticipants (N=1209), were recruited online and completed three scales: pregnancy-related anxiety, general anxiety and depression. Multiple regression assessed the unique contribution of general anxiety and depression (predictors) to pregnancy-related anxiety scores (criterion) for each trimester.ResultsAcross pregnancy, general anxiety and depression explained only 2–23% of the variance in the pregnancy-related anxiety scores. Anxiety and depression showed small unique contributions for some trimesters and specific areas of concern, ranging from 2 to 11%. Comparisons to the original Huizink study showed most results were comparable.ConclusionsThe methodology and more detailed analyses employed addressed noted limitations of the Huizink study. Findings that the contribution of general anxiety and depression to the variance in pregnancy-related anxiety scores was low, supports previous conclusions that pregnancy-related anxiety is a discrete anxiety type. Recognition of this unique anxiety (associated with many deleterious outcomes) may provide opportunity for prenatal screening/early intervention, potentially resulting in improved pregnancy outcomes. Limitations include no exclusion of women deemed as high-risk pregnancy and the pregnancy-related anxiety scale limited in its ability to fully assess this anxiety type.



https://ift.tt/2rLwXUF

Postnatal gestational diabetes mellitus follow-up: Perspectives of Australian hospital clinicians and general practitioners

Publication date: Available online 4 May 2018
Source:Women and Birth
Author(s): Catherine Kilgour, Fiona Elizabeth Bogossian, Leonie Callaway, Cindy Gallois
ProblemThe reasons for low postnatal screening rates for women with gestational diabetes mellitus are not well understood. Multiple care providers, settings and changes to diagnostic criteria, may contribute to confusion over postnatal care. Quality of communication between clinicians may be an important influence for the completion of postnatal gestational diabetes mellitus follow-up.AimDescribe and analyse communication processes between hospital clinicians (midwives, medical, allied staff) and general practitioners who provide postnatal gestational diabetes mellitus care.MethodsPurposive sampling and convergent interviews explored participants' communication experiences providing gestational diabetes mellitus postnatal follow-up. Data were analysed with Leximancer automated content analysis software; interpretation was undertaken using Communication Accommodation Theory.Setting and participantsClinicians who provided maternity care at a tertiary referral hospital (n=13) in Queensland, Australia, and general practitioners (n=16) who provided maternity shared care with that hospital between December 2012 and July 2013.FindingsThematic analysis identified very different perspectives between the experiences of General Practitioners and hospital clinicians; six themes emerged. General practitioners were concerned about themes relating to discharge summaries and follow-up guidelines. In contrast, hospital clinicians were more concerned about themes relating to gestational diabetes mellitus antenatal care and specialist clinics. Two themes, gestational diabetes mellitus women and postnatal checks were shared.ConclusionGestational diabetes mellitus follow-up is characterised by communication where general practitioners appear to be information seekers whose communication needs are not met by hospital clinicians. Midwives are ideally placed to assist in improving communication and postnatal gestational diabetes mellitus follow-up.



https://ift.tt/2L5QWXc

“Trying to give birth naturally was out of the question”: Accounting for intervention in childbirth

Publication date: Available online 4 May 2018
Source:Women and Birth
Author(s): Lindsay Cole, Amanda LeCouteur, Rebecca Feo, Hannah Dahlen
ProblemStudies of women's childbirth preferences repeatedly show that natural birth remains highly valued, yet the majority of births involve some form of medical intervention. Reasons for this lack of correspondence have typically been investigated through interviews and focus-groups with women. Relatively little research explores the ways in which women describe their experiences of childbirth outside of such research settings.BackgroundMost maternity services promote woman-centred care, whereby women are encouraged to take active roles in deciding how to give birth. However, recent research indicates that women often report feeling disempowered during labour and birth in hospital settings.AimWe sought to examine how women account for use of medical intervention in hospitals by examining narratives posted on online discussion forums.MethodA thematic analysis of 106 publically available birth stories, sourced using the Internet search terms 'birth story', and 'birth narrative', was undertaken.FindingsMedical interventions in childbirth were routinely described as unwanted, yet as unavoidable, and two types of account were typically drawn on to explain their use: Protection of the baby/mother; and inflexible hospital policy/practice. We examine these two types of account, focusing on how their design oriented to the discordance between mothers' reported desires for a natural birth, and their experiences in hospital.ConclusionThe experience of medical intervention in childbirth is routinely oriented to as a matter that requires explanation or account in online birth narratives. Women repeatedly referred to their preference to avoid intervention, but described being unable to do so in hospital.



https://ift.tt/2rL7tH3

Cessation of breastfeeding in association with oxytocin administration and type of birth. A prospective cohort study

Publication date: Available online 10 May 2018
Source:Women and Birth
Author(s): Aurora Fernández-Cañadas Morillo, Modesto Durán Duque, Ana B. Hernández López, Cristina Muriel Miguel, Pilar Pérez Riveiro, Angel Salcedo Mariña, Ana Royuela Vicente, María L. Casillas Santana, Miguel A. Marín Gabriel
BackgroundSome studies have suggested an association between synthetic oxytocin administration and type of birth with the initiation and consolidation of breastfeeding.AimThis study aimed to test whether oxytocin administration and type of birth are associated with cessation of exclusive breastfeeding at different periods. A second objective was to investigate whether the administered oxytocin dose is associated with cessation of exclusive breastfeeding.MethodsWe conducted a prospective cohort study (n=529) in a tertiary hospital. Only full-term singleton pregnancies were included. Four groups were established based on the type of birth (vaginal or cesarean) and the intrapartum administration of oxytocin. Follow-up was performed to evaluate the consolidation of exclusive breastfeeding at 1, 3 and 6months.FindingsDuring follow-up, the proportion of exclusive breastfeeding decreased in all groups. After adjusting for confounding variables, the group with cesarean birth without oxytocin (planned cesarean birth) had the highest risk of cessation of exclusive breastfeeding (odds ratio [95% confidence interval], 2.51 [1.53–4.12]). No association was found between the oxytocin dose administered during birth and puerperium period and the cessation of exclusive breastfeeding.ConclusionPlanned cesarean birth without oxytocin is associated with the cessation of exclusive breastfeeding at 1, 3 and 6months of life. It would be desirable to limit elective cesarean births to essentials as well as to give maximum support to encourage breastfeeding in this group of women. The dose of oxytocin given during birth and puerperium period is not associated with cessation of exclusive breastfeeding.



https://ift.tt/2IkJUjp

A qualitative exploration of techniques used by expert midwives to preserve the perineum intact

Publication date: Available online 3 May 2018
Source:Women and Birth
Author(s): C. Begley, K. Guilliland, L. Dixon, M. Reilly, C. Keegan, C. McCann, V. Smith
BackgroundThe perineum stretches during birth to allow passage of the baby, but 85% of women sustain some degree of perineal trauma during childbirth, which is painful post-partum. Episiotomy rates vary significantly, with some countries having rates of >60%. Recent Irish and New Zealand studies showed lower severe perineal trauma and episiotomy rates than other countries.AimTo explore expert Irish and New Zealand midwives' views of the skills that they employ in preserving the perineum intact during spontaneous vaginal birth.MethodsFollowing ethical approval a qualitative, descriptive study was undertaken. Semi-structured, recorded, interviews were transcribed and analysed using the constant comparative method. Expert midwives employed in New Zealand and one setting in Ireland, were invited to join the study. "Expert" was defined as achieving, in the preceding 3.5 years, an episiotomy rate for nulliparous women of <11.8%, a 'no suture' rate of 40% or greater, and a severe perineal tear rate of <3.2%. Twenty-one midwives consented to join the study.ResultsFour core themes emerged: 'Calm, controlled birth', 'Position and techniques in early second stage', 'Hands on or off?' and 'Slow, blow and breathe the baby out.' Using the techniques described enabled these midwives to achieve rates, in nulliparous women, of 3.91% for episiotomy, 59.24% for 'no sutures', and 1.08% for serious lacerations.ConclusionsThis study provides further understanding of the techniques used by expert midwives at birth. These findings, combined with existing quantitative research, increases the evidence on how to preserve the perineum intact during spontaneous birth.



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Making the hidden seen: A narrative analysis of the experiences of Assumption of Care at birth

Publication date: Available online 30 April 2018
Source:Women and Birth
Author(s): Christine A. Marsh, Jenny Browne, Jan Taylor, Deborah Davis
BackgroundBeing involved in any child protection system is complex and multifaceted and none more so than in non-voluntary Assumption of Care which occurs in New South Wales when, for child protection concerns, the Department of Family and Community Services removes a newborn baby from her/his mother.ObjectiveThis research studied childbearing women's and professionals' experiences of Assumption of Care at birth to increase understanding of individual participants' stories, how they made sense of meanings and how these experiences framed their lives.MethodA narrative inquiry framework guided interviews with four groups: childbearing women, midwives, social workers and Family and Community Services case managers. Holistic form was used for reading, interpreting and analysing the narratives.FindingsThis research found unwanted emotional (isolation, shame, guilt, loss, disenfranchised grief) and physical consequences (depression, substance abuse complications) for women experiencing an Assumption of Care at the time of birth. There were also conflicting ethical and moral positions for the professionals involved. The use/abuse of power, concealment of facts and disenfranchised grief were identified as intertwined plots that caused or increased tensions.DiscussionBoth the women and the professionals felt pressure from trying to achieve competing and overlapping roles. The unwanted effects of Assumption of Care are exacerbated by the current child protection and maternity care systems.ConclusionTo address the tensions raised in this study, we suggest a two-fold change to maternity care for women at risk of an Assumption of Care: a therapeutic justice model of maternity care and continuity of midwifery care with a dedicated midwife. Introducing these changes could increase women's and children's safety and wellbeing.



https://ift.tt/2IitnMR

Women’s experience of midwife-led counselling and its influence on childbirth fear: A qualitative study

Publication date: Available online 27 April 2018
Source:Women and Birth
Author(s): Birgitta Larsson, Ingegerd Hildingsson, Elin Ternström, Christine Rubertsson, Annika Karlström
BackgroundWomen with childbirth fear have been offered counseling by experienced midwives in Sweden for decades without evidence for its effectiveness, in terms of decrease in childbirth fear. Women are usually satisfied with the counselling. However, there is a lack of qualitative data regarding women's views about counselling for childbirth fear.AimTo explore women's experiences of midwife-led counselling for childbirth fear.MethodA qualitative interview study using thematic analysis. Twenty-seven women assessed for childbirth fear who had received counselling during pregnancy at three different hospitals in Sweden were interviewed by telephone one to two years after birth.FindingsThe overarching theme 'Midwife-led counselling brought positive feelings and improved confidence in birth' was identified. This consisted of four themes describing 'the importance of the midwife' and 'a mutual and strengthening dialogue' during pregnancy. 'Coping strategies and support enabled a positive birth' represent women's experiences during birth and 'being prepared for a future birth' were the women's thoughts of a future birth.ConclusionsIn this qualitative study, women reported that midwife-led counselling improved their confidence for birth through information and knowledge. The women experienced a greater sense of calm and preparedness, which increased the tolerance for the uncertainty related to the birthing process. This, in turn, positively affected the birth experience. Combined with a feeling of safety, which was linked to the professional support during birth, the women felt empowered. The positive birth experience strengthened the self-confidence for a future birth and the childbirth fear was described as reduced or manageable.



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Veiled midwifery in the baby factory — A grounded theory study

Publication date: Available online 27 April 2018
Source:Women and Birth
Author(s): Malin Hansson, Ingela Lundgren, Gunnel Hensing, Ing-Marie Carlsson
BackgroundMidwives' professional role has been changing drastically over time, from handling births in home settings to being part of a team in labour wards in hospitals. This demands a greater effort of interprofessional collaboration in childbirth care.AimExplore midwives' work in a hospital-based labour ward from the perspectives of other professions, working in the same ward.MethodClassical grounded theory, using a constant comparative analysis, was applied to focus group interviews with obstetricians, assistant nurses and managers to explore their views of midwifery work during childbirth.FindingsThe substantive theory of 'veiled midwifery' emerged as an explanation of the social process between the professions in the 'baby factory' context. The other professionals perceive midwifery through a veil that filters the reality and only permits fragmentary images of the midwives' work. The main concern for the other professions was that the midwives were 'marching to own drum'. The midwives were perceived as both in dissonance with the baby factory, and therefore hard to control, or, alternatively more compliant with the prevailing rhythm. This caused an unpredictability and led to feelings of frustration and exclusion. Which in turn resulted in attempts to cooperate and gain access to the midwifery world, by using three unveiling strategies: Streamlining, Scrutinising and Collaborating admittance.ConclusionsFindings provide a theoretical conceptualisation of a 'veiled midwifery 'that causes problems for the surrounding team. This generates a desire to streamline and control midwifery in order to increase interprofessional collaboration.



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Community engagement in the Aboriginal Families Study: Strategies to promote participation

Publication date: Available online 24 April 2018
Source:Women and Birth
Author(s): Donna Weetra, Karen Glover, Roxanne Miller, Rikki Wilson, Cathy Leane, Deanna Stuart-Butler, Amanda Mitchell, Deirdre Gartland, Stephanie Brown
BackgroundAboriginal women and families are under-represented in Australian research on pregnancy and childbirth. The Aboriginal Families Study aimed to investigate the views and experiences of a representative sample of women giving birth to an Aboriginal baby in South Australia between July 2011 and June 2013, using methods designed to respect Aboriginal culture and communities.MethodsA team of 12 Aboriginal researchers facilitated community engagement and recruitment of Aboriginal and non-Aboriginal mothers of Aboriginal infants in urban, regional and remote areas of South Australia over a two-year period.ResultsA total of 344 women took part, around a quarter of all Aboriginal women giving birth in South Australia in the study period (39% urban, 35% regional and 25% from remote areas). Participants were representative in relation to maternal age (mean age of 25 years, range=15–43 years). Over half of women (56%) first heard about the study via a member of the fieldwork team making contact with them through community connections. Other major sources of recruitment were: Aboriginal health services/programs (20%) and public maternity hospitals (16%). Almost all of the women (95%) recruited via community networks of the fieldwork team completed the questionnaire. In contrast, 51% of women recruited via public hospitals completed the questionnaire (odds ratio=0.1, 95% confidence interval 0.0–0.1, p<0.001).ConclusionsAboriginal researchers' community knowledge and leadership is critical to the conduct of successful Aboriginal health research. High levels of participation in research by 'harder to reach' populations are achievable when researchers take time to build relationships and work in partnership with communities.



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The nature of labour pain: An updated review of the literature

Publication date: Available online 22 April 2018
Source:Women and Birth
Author(s): Laura Y. Whitburn, Lester E. Jones, Mary-Ann Davey, Susan McDonald
BackgroundThe pain experience associated with labour is complex. Literature indicates psychosocial and environmental determinants of labour pain, and yet methods to support women usually target physiological attributes via pharmacological interventions.AimTo provide an update of our understanding of labour pain based on modern pain science. The review aims to help explain why women can experience labour pain so differently — why some cope well, whilst others experience great suffering. This understanding is pertinent to providing optimal support to women in labour.MethodA literature search was conducted in databases Medline, Cumulative Index to Nursing and Allied Health Literature and PsycINFO, using search terms labor/labour, childbirth, pain, experience and perception. Thirty-one papers were selected for inclusion.FindingsLabour pain is a highly individual experience. It is a challenging, emotional and meaningful pain and is very different from other types of pain. Key determinants and influences of labour pain were identified and grouped into cognitive, social and environmental factors.ConclusionIf a woman can sustain the belief that her pain is purposeful (i.e. her body working to birth her baby), if she interprets her pain as productive (i.e. taking her through a process to a desired goal) and the birthing environment is safe and supportive, it would be expected she would experience the pain as a non-threatening, transformative life event. Changing the conceptualisation of labour pain to a purposeful and productive pain may be one step to improving women's experiences of it, and reducing their need for pain interventions.



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Awareness of Listeriosis and Methylmercury toxicity public health recommendations and diet during pregnancy

Publication date: Available online 17 April 2018
Source:Women and Birth
Author(s): Shao Jia Zhou, Rebecca L. Greco, Rosalie Grivell, Jennie Louise, Andrea Deussen, Jodie Dodd, Lisa J. Moran
BackgroundAwareness of Listeriosis and Methylmercury toxicity recommendations are associated with decreased intake of high-risk foods. Whether awareness of the recommendations affect dietary quality of pregnant women in Australian is unknown.AimTo evaluate awareness of Listeriosis and Methylmercury toxicity recommendations during pregnancy and its impact on dietary quality.MethodsPregnant women (n=81) were recruited from antenatal clinics. Awareness of Listeriosis and Methylmercury toxicity recommendations and high-risk foods consumption were assessed via questionnaire at 10–23 weeks gestation. Diet quality was measured using the 2005 Healthy Eating Index using a validated food frequency questionnaire at 10–23 and 34–36 weeks gestation.FindingsA higher proportion of women were aware of Methylmercury toxicity compared with Listeriosis recommendations (75.3 vs. 59.2%, p<0.001). The proportion of women who decreased or avoided consumption of certain high-risk Listeriosis foods were higher in those who were aware compared with those who were unaware of Listeriosis recommendations [raw fish (96.0 vs 69.2%, p=0.046), soft-serve ice cream (93.9 vs 58.3%, p=0.004) and alfalfa/bean sprouts (68.7 vs 28.5%, p=0.006)]. A large proportion of women (96.8%) met recommendations for limiting consumption of high Methylmercury fish. There was no difference in the change in dietary quality over pregnancy regardless of women's awareness of the recommendations.Discussion and conclusionsAwareness of Listeriosis and Methylmercury toxicity recommendations has little impact on dietary quality of pregnant women in this small study. Further research in a large representative population of pregnant women is needed to confirm our findings and to optimise dietary quality during pregnancy.



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Reasons for substance use continuation and discontinuation during pregnancy: A qualitative study

Publication date: Available online 16 April 2018
Source:Women and Birth
Author(s): Kiri A. Latuskie, Naomi C.Z. Andrews, Mary Motz, Tom Leibson, Zubin Austin, Shinya Ito, Debra J. Pepler
BackgroundSubstance use during pregnancy is a major public health concern, stemming from potential physical and psychosocial harms to both the mother and child.PurposeTo understand women's experiences using substances during pregnancy and the reasons that women continue and/or discontinue using substances.MethodsFocus groups were conducted with women who attended an early intervention program for pregnant or parenting women with substance use issues.ResultsWomen identified that external and internal stressors, feelings of guilt and low-self efficacy, and a lack of understanding of the scientific and medical consequences of substance use contributed to their continued substance use. Conversely, women highlighted the importance of high self-efficacy and the quality of relationships when trying to make positive changes to their substance use during pregnancy.ConclusionsRecommendations are proposed for easier access to and more comprehensive services. Healthcare professionals and service providers should offer non-judgmental care by building high-quality relationships with pregnant women with substance use issues, to increase these women's self-efficacy and empower them to discontinue substance use.



https://ift.tt/2L1F48u

Balance and mobility training at home using Wii Fit in children with cerebral palsy: a feasibility study

Objectives

To investigate whether balance and mobility training at home using Wii Fit is feasible and can provide clinical benefits.

Design

Single-group, pre–post intervention study.

Setting

Participants' home.

Participants

20 children with cerebral palsy (6–12 years).

Intervention

Participants undertook 8 weeks of home-based Wii Fit training in addition to usual care.

Main measures

Feasibility was determined by adherence, performance, acceptability and safety. Clinical outcomes were strength, balance, mobility and participation measured at baseline (preintervention) and 8 weeks (postintervention).

Results

The training was feasible with 99% of training completed; performance on all games improved; parents understood the training (4/5), it did not interfere in life (3.8/5), was challenging (3.9/5) and would recommend it (3.9/5); and there were no injurious falls. Strength increased in dorsiflexors (Mean Difference (MD) 2.2 N m, 95% CI 1.1 to 3.2, p<0.001), plantarflexors (MD 2.2 N m, 95% CI 1.3 to 3.1, p<0.001) and quadriceps (MD 7.8 N m, 95% CI 5.2 to 10.5, p<0.001). Preferred walking speed increased (MD 0.25 m/s, 95% CI 0.09 to 0.41, p<0.01), fast speed increased (MD 0.24 m/s, 95% CI 0.13 to 0.35, p<0.001) and distance over 6 min increased (MD 28 m, 95% CI 10 to 45, p<0.01). Independence in participation increased (MD 1.4 out of 40, 95% CI 0.0 to 2.8, p=0.04).

Conclusions

Balance and mobility training at home using Wii Fit was feasible and safe and has the potential to improve strength and mobility, suggesting that a randomised trial is warranted.

Trial registration number

ACTRN12616001362482.



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The guiding role of bone metabolism test in osteoporosis treatment.

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The guiding role of bone metabolism test in osteoporosis treatment.

Am J Clin Exp Immunol. 2018;7(2):40-49

Authors: Zhang W, Yang GJ, Wu SX, Li DQ, Xu YB, Ma CH, Wang JL, Chen WW

Abstract
Osteoporosis (OP) and osteoporotic fractures are becoming a serious health care issue in the world. Calcium and vitamin D are the basic treatment for osteoporosis. Nonetheless, they do not effectively reduce the incidences of fracture. Currently approved treatments for osteoporosis include selective estrogen receptor modulators (SERMs), bisphosphonates, denosumab, teriparatide, calcitonin and others. However, the appearance of some adverse effects including atypical fracture and breast cancer has limited long-term treatments above mentioned. Therefore, treatment decision should be made on an individual basis, taking into account the relative benefits and risks in different patients. Bone metabolism test helps to assess the patient's condition, which may ultimately lead to therapeutic options and better clinical outcomes.

PMID: 29755856 [PubMed]



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Association of HSP90B1 genetic polymorphisms with efficacy of glucocorticoids and improvement of HRQoL in systemic lupus erythematosus patients from Anhui Province.

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Association of HSP90B1 genetic polymorphisms with efficacy of glucocorticoids and improvement of HRQoL in systemic lupus erythematosus patients from Anhui Province.

Am J Clin Exp Immunol. 2018;7(2):27-39

Authors: Sun XX, Li SS, Zhang M, Xie QM, Xu JH, Liu SX, Gu YY, Pan FM, Tao JH, Xu SQ, Liu S, Cai J, Wang DG, Qian L, Wang CH, Lian L, Xiao H, Chen PL, Liang CM, Fang YB, Zhou Q, Huang HL, Su H, Pan HF, Ye DQ, Zou YF

Abstract
Objective: The aim of this study was to investigate the associations between HSP90B1 gene polymorphisms and the efficacy of glucocorticoids (GCs) and the improvement of health-related quality of life (HRQoL) in Anhui patients with systemic lupus erythematosus (SLE). Method: A total of 305 patients with SLE were recruited to the study. These patients were treated with GCs for 12 weeks and classified into two groups (sensitivity and insensitivity) according to the response to GCs measured by the scores on SLE disease activity index (SLEDAI). The HRQoL of SLE patients were evaluated by 36-item Short Form Health Survey (SF-36) at baseline and 12 weeks respectively. HapMap database and Haploview software were used to select HSP90B1 gene tag single nucleotide polymorphisms (SNPs). Benjamini & Hochberg (BH) method based on false discovery rate (FDR) was used for multiple testing correction. Results: A total of 291 patients were included in final data analysis with 14 patients excluded due to loss to follow-up. Among these patients, 160 patients were sensitive to GCs and 131 patients were insensitive to GCs. Twelve tag SNPs of HSP90B1 gene were selected. The rs12426382 polymorphism was associated with the efficacy of GCs (dominant model: crude OR=0.514, 95% CI=0.321-0.824, P=0.006; adjusted OR=0.513, 95% CI=0.317-0.831, P=0.007). After BH correction, there was no association between rs12426382 polymorphism and efficacy of GCs (PBH =0.084). In haplotype analysis, the haplotype CCCGAACATCCC (OR=2.273, 95% CI=1.248-4.139, P=0.006) and CTGGGACGTTC (OR=0.436, 95% CI=0.208-0.916, P=0.025) showed significant associations with the efficacy of GCs. After corrected by BH method, CCCGAACATCCC was still associated with the efficacy of GCs (PBH =0.048). The rs3794241, rs1165681, rs2722188, rs3794240 and rs10861147 polymorphisms were associated with the improvement of HRQoL among SLE patients (P < 0.05). But no association existed after the correction of BH method (P > 0.05). Conclusions: The results of this study demonstrated that HSP90B1 genetic polymorphisms might be associated with the efficacy of GCs, but not associated with the improvement of HRQoL in Anhui population with SLE.

PMID: 29755855 [PubMed]



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Neuroanatomical autonomic substrates of brainstem-gut circuitry identified using transsynaptic tract-tracing with pseudorabies virus recombinants.

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Neuroanatomical autonomic substrates of brainstem-gut circuitry identified using transsynaptic tract-tracing with pseudorabies virus recombinants.

Am J Clin Exp Immunol. 2018;7(2):16-24

Authors: He ZG, Wang Q, Xie RS, Li YS, Hong QX, Xiang HB

Abstract
To investigate autonomic substrates of brainstem-gut circuitry identified using trans-synaptic tracing with pseudorabies virus (PRV)-152, a strain that expresses enhanced green fluorescent protein, and PRV-614, a strain that expresses enhanced red fluorescent protein, injecting into the rat rectum wall. 3-7 days after PRV-152 injection, spinal cord and brainstem were removed and sectioned, and processed for PRV-152 visualization using immunofluorescence labeling against PRV-152. 6 days after PRV-614 injection, brainstem was sectioned and the neurochemical phenotype of PRV-614-positive neurons was identified using double immunocytochemical labeling against PRV-614 and TPH. We observed that the largest number of PRV-152- or PRV-614-positive neurons was located in the gigantocellular reticular nucleus (Gi), lateral paragigantocellular (LPGi), rostral ventrolateral reticular nucleus (RVL), solitary tract nucleus (Sol), locus coeruleus (LC), raphe magnus nucleus (RMg), subcoeruleus nucleus (SubCD). Double-labeled PRV-614/tryptophan hydroxylase (TPH) neurons were concentrated in the RMg, LPGi and Sol. These brainstem neurons are candidates for relaying autonomic command signals to the gut. The autonomic substrate of brainstem-gut circuitry likely plays an important role in mediating different aspects of stress behaviors.

PMID: 29755854 [PubMed]



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Reg3β from cardiomyocytes regulated macrophage migration, proliferation and functional skewing in experimental autoimmune myocarditis.

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Reg3β from cardiomyocytes regulated macrophage migration, proliferation and functional skewing in experimental autoimmune myocarditis.

Am J Clin Exp Immunol. 2018;7(2):8-15

Authors: Zhou S, Jiang H, Wang H, Lu H, Chen R, Xu H, Su Z, Shao X

Abstract
Macrophages play critical roles in inflammatory initiation, development, resolution and cardiac regeneration of myocarditis. However, Reg3β, as a member of regenerating family of proteins, contributes to dedifferentiation of injury cardiomyocytes as well as cardiac function remodeling. It remains unclear whether Reg3β was associated with macrophages reprogramming during autoimmune myocarditis. Our results showed that Reg3β could effectively recruit macrophages, promoted their proliferation and phagocytosis, and facilitated their polarized into M2 macrophages. Macrophage, especially M1 phenotype contributed to Reg3β production by cardiomyocytes. Our data also indicated that Reg3β was involved in self-protection mechanism following cardiac injury or stress. This suggests that Reg3β might be a critically protective factor of myocardium.

PMID: 29755853 [PubMed]



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Clinicopathological analysis of immunohistochemical expression of retinoic acid-related orphan receptor-γt in peripheral T-cell lymphoma, not otherwise specified

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is cytologically and phenotypically heterogeneous. Retinoic acid-related orphan receptor-γt (RORγt) is a transcription factor that regulates the differentiation of naïve CD4+ helper T-cells to Th17 cells. In the present study, we immunohistochemically confirmed the expression of RORγt in PTCL-NOS. Pathological and clinical investigations were performed for 170 cases of PTCL-NOS. RORγt-positive cases accounted for 17.6% (30/170) of the total cases and they showed a significantly higher frequency of CD8 positivity (P=.033), lower counts of white blood cells (P=.030) and neutrophils (P=.039) in the peripheral blood, higher levels of hypergammaglobulinemia (P=.031), a higher frequency of a complete response (P=.009), and a tendency for a lower International Prognostic Index (IPI) (P=.061) and better overall survival (P=.0806).

https://ift.tt/2GkoFsj