Δευτέρα, 13 Νοεμβρίου 2017

Is the incidence of esophageal adenocarcinoma increasing in Japan? Trends from the data of a hospital-based registration system in Akita Prefecture, Japan

Abstract

Background

At present, squamous cell carcinoma accounts for most esophageal cancers in Japan; however, there is concern that the incidence of esophageal adenocarcinoma in Japan is increasing in comparison to Western countries. Akita Prefecture, with a population of 1 million, has the highest rate of esophageal cancer-associated mortality in Japan; the vast majority of these cases are squamous cell carcinoma. The aim of the present study was to investigate the latest trends in the incidence of esophageal adenocarcinoma in Akita Prefecture using a registration system.

Methods

We examined the data from a collaborative hospital-based registration system for cancer patients. Eleven of the main hospitals in Akita Prefecture participate in this system, which covers 90% of the cancer cases in the region and which provides near population-based data. Using this registration system, we examined the sequential trends in the percentage of adenocarcinoma cases in relation to total esophageal cancer cases in Akita Prefecture from 2007 to 2014.

Results

In 2007–2014, a total of 2527 esophageal cancer patients were registered in the system. Among these, only 43 (1.8%) had adenocarcinoma. However, the number of adenocarcinoma patients gradually increased from 1 case in 2007 to 14 cases in 2014. Consequently, the percentage of adenocarcinoma cases showed a significant increase from 0.66% in the first 4 years of the study period to 2.5% in the latter 4 years of the study period (P < 0.01).

Conclusions

The latest hospital-based registration data for 2007–2014 suggest that the incidence of esophageal adenocarcinoma may have begun to increase in Akita Prefecture; this may reflect recent trends in other parts of Japan.



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Regulation of TMEM16A/ANO1 and TMEM16F/ANO6 ion currents and phospholipid scrambling by Ca2+ and plasma membrane lipid

Abstract

TMEM16/anoctamin proteins form Ca2+ activated ion channels or phospholipid scramblases. We found that both TMEM16A/ANO1 and TMEM16F/ANO6 produced Cl currents when activated by intracellular Ca2+, but only TMEM16F was able to expose phosphatidylserine to the outer leaflet of the plasma membrane. Mutations within TMEM16F or TMEM16A/F chimeras similarly changed Cl currents and phospholipid scrambling, suggesting the same intramolecular pathway for Cl and phospholipids. When overexpressed, TMEM16A and TMEM16F produced spontaneous Cl currents at 37°C even at resting intracellular Ca2+ levels, which was abolished by inhibition of phospholipase A2 (PLA2). Inversely, activation of PLA2 or application of active PLA2, as well as lipid peroxidation induced by reactive oxygen species (ROS) using staurosporine or tert-butyl hydroperoxide, enhanced ion currents by TMEM16A/F and in addition activated phospholipid scrambling by TMEM16F. Thus TMEM16 proteins are activated by an increase in intracellular Ca2+, or independent of intracellular Ca2+ by modifications occurring in plasma and intracellular membrane phospholipids. These results may help to understand, why regions distant to the TMEM16 pore and the Ca2+ binding sites control Cl currents and phospholipid scrambling. Regulation of TMEM16 proteins through modification of membrane phospholipids occurs during regulated cell death such as apoptosis and ferroptosis. It contributes to inflammatory and nerve-injury induced hypersensitivity and generation of pain and therefore provides a regulatory mechanism particularly relevant during disease.

This article is protected by copyright. All rights reserved



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Which Individuals To Choose To Update the Reference Population? Minimizing the Loss of Genetic Diversity in Animal Genomic Selection Programs

Genomic selection is commonly used in livestock and increasingly in plant breeding. Relying on phenotypes and genotypes of a reference population, genomic selection allows performance prediction for young individuals having only genotypes. This is expected to achieve fast high genetic gain but with a potential loss of genetic diversity. Existing methods to conserve genetic diversity depend mostly on the choice of the breeding individuals. In this study we propose a modification of the reference population composition to mitigate diversity loss. Since the high cost of phenotyping is the limiting factor for genomic selection our findings are of major economic interest. This study aims to answer the following questions: How would decisions on the reference population affect the breeding population? How to best select individuals to update the reference population and balance maximizing genetic gain and minimizing loss of genetic diversity? We investigated three updating strategies for the reference population: random, truncation and optimal contribution strategies. Optimal contribution maximizes genetic merit for a fixed loss of genetic diversity. A French Montbéliarde dairy cattle population with 50K SNP chip genotypes and simulations over ten generations were used to compare these different strategies using milk production as the trait of interest. Candidates were selected to update the reference population. Prediction bias and both genetic merit and diversity were measured. Changes in the reference population composition slightly affected the breeding population. Optimal contribution strategy appeared to be an acceptable compromise to maintain both genetic gain and diversity in the reference and the breeding populations.



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Effects of somatosensory electrical stimulation on motor function and cortical oscillations

Few patients recover full hand dexterity after an acquired brain injury such as stroke. Repetitive somatosensory electrical stimulation (SES) is a promising method to promote recovery of hand function. However...

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A composite robotic-based measure of upper limb proprioception

Proprioception is the sense of the position and movement of our limbs, and is vital for executing coordinated movements. Proprioceptive disorders are common following stroke, but clinical tests for measuring i...

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The effect of reducing EEG electrode number on the visual interpretation of the human expert for neonatal seizure detection

Optimising neuro-critical care in the newborn has become a high priority issue in paediatrics (Abend et al. 2011; Bonifacio et al. 2011; Glass et al. 2016). One of the key challenges in neuro-critical care is to provide brain monitoring that is continuous and uninterrupted in settings where personnel are changing constantly, neurophysiological support is limited, and an array of other medical devices are competing for cotside attention and placements. These practical considerations have led neonatologists to use a biparietal (P3-P4), or more recently, a two-channel (centro/fronto-parietal) derivation, to provide a measurement of neurological function (van Rooij et al.

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Be ready to respond with new certified safety kits, available from theEMSstore

COATESVILLE, Pa. — theEMSstore, a trusted, top supplier of critical supplies geared toward EMS professionals, is excited to now offer multi-purpose, easy-to-maintain and refill Certified Safety First Aid Kits. Accidents and injuries can happen at any moment, in any setting. For over 50 years, Certified Safety Mfg. has cultivated an uninterrupted record of excellence in bringing innovative first ...

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Unusual iliac crest stress fracture in a marathoner: A Case Report

This case presentation describes a 50-year-old healthy woman who developed left sided hip pain while training for the Boston Marathon. Magnetic Resonance Imaging (MRI) demonstrates a stress fracture of the left iliac body. This injury is unique in that it did not occur in the setting of low bone mineral density and it does not fall into the current published radiographic categorization based on location of injury. This case illustrates an uncommon and atypical bone stress injury in an endurance athlete.

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Prophylactic rtPA in the Prevention of Line-associated Thrombosis and Infection in Short Bowel Syndrome.

Background: Central venous access devices (CVADs) are essential for total parenteral nutrition administration in patients with short bowel syndrome (SBS). However, they are fraught with complications including infection and venous thromboembolism (VTE), which increases associated morbidity and mortality in this population. There is evidence linking the development of CVAD-associated thrombosis and line-related infection. Thus, it has been postulated that prevention of catheter-related clot formation could minimize the risk of infection originating from the catheter. Recombinant tissue plasminogen activator (rtPA, AlteplaseTM), lyses clots by binding plasmin-bound fibrin in a clot and cleaving plasminogen to plasmin; moreover, it is widely utilized to clear occluded CVADs. Methods: Prophylactic rtPA lock therapy in children with SBS was evaluated as a single site pilot study to minimize line-associated-VTE, infection, need for line replacement and hospitalization at the Children's Hospital of Pittsburgh of UPMC. rtPA lock therapy was administered by parents/caregivers on a weekly basis over a 6-month time period in place of heparin lock therapy. Comparisons were made between line-associated complications in the cohort in the 6 months prior to study versus during the study period. Results: Six out of eight subjects completed the study over a one-year time period. As a group, subjects experienced a significant decrease in the number of line-associated bloodstream infections from a mean of 1.9 infections in the 6 months prior to the study to a mean of 0.5 infections (p = 0.025). There was no change in the need for line replacement amongst subjects while on study. The primary outcome of VTE was not found in the cohort, and it is unclear whether rtPA lock therapy contributed to the lack of thrombosis development. Given the success of rtPA in this pilot study in reducing bloodstream infections, further investigation or rtPA lock therapy in SBS patients is warranted. (C) 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Expediting Drug Development for Pediatric Inflammatory Bowel Disease: A Discussion with Stakeholders.

Objectives: Lack of scientific consensus on efficacy endpoints and outcome assessments presents a hurdle for global drug development in pediatric inflammatory bowel disease (IBD). Multiple stakeholders participated in a meeting November 2015, sponsored by The Pediatric IBD Foundation, which is a 501c3 organization formed by parents of children with IBD whose mission is to improve the lives of children with Crohn's disease and ulcerative colitis by supporting innovative research and educational programs ( www.pedsibd.org). Wth representatives of the Federal Drug Administration (FDA), European Medicines Agency (EMA), pediatric gastroenterologists, and representatives of the pharmaceutical industry, this meeting was organized to harmonize present thinking about various aspects of global drug development in pediatric IBD. The meeting was designed to be interactive, allowing participants from the pharmaceutical industry, regulatory agencies, academia and clinical practice an opportunity to collaborate in a public forum and to identify potential strategies to expedite drug evaluation in children. Methods: Prior to the meeting, a questionnaire focused on the hurdles hindering approval of medications used to treat children with IBD was sent to all participants as well as other pediatric gastroenterologists in North America and Europe with expertise in IBD. Responses were reviewed by the steering committee and results presented at the meeting. Following the presentation of the survey, participants were divided into small groups comprised of representatives from academia, industry, regulatory agencies, and members of the Pediatric IBD Foundation and assigned the task of working together to find solutions to the hurdles that had been identified. Results: Hurdles hindering approval included: (i) pediatric trials start later in the development process; (ii) lack of enrollment in pediatric trials; (iii) lack of monitoring safety registries that might expedite approval; (iv) different priorities among stakeholders. Conclusions: This one-day meeting discussed how to expedite pediatric drug development in IBD therapy. Hurdles for achieving approvals of pediatric indications for treatments of IBD were identified. (C) 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Avoiding Small Intestinal Biopsies for Diagnosis of Celiac Disease in Children: A Reliable Strategy for All Patients?.

Background: Current reports applying ESPGHAN exception criteria (EEC) to diagnose celiac disease (CD) without duodenal biopsies indicate that a high percentage of patients with CD may be identified when applied correctly in specialized settings. However, application of the EEC in "daily life conditions" at the different levels of medical services is not clear. Methods: EEC was applied to 130 pediatric patients evaluated for CD at five public hospitals in Santiago, Chile, during 2010-2015. Clinical presentation, serum anti-tissue transglutaminase 2 (TTG) and anti-endomysium antibodies (EMA), genotyping and small intestinal histology were obtained from clinical charts. Results: 78/130 patients reviewed had some of the data required for analysis, but EMA was determined in 54% and genotyping in 2.3% of patients, limiting the study. After offering free genotyping, only 12/78 (15%) had all data required for EEC application. In this small group, 10/12 (83.3%) patients could avoid duodenal biopsies and two (16.7%) with potential CD were misdiagnosed. Main reasons for not doing EMA and genotyping were that they are expensive, unavailable in the local health-care center and considered "not necessary" for diagnosis. Conclusion: Limited resources in clinical settings reduce availability of EMA and genotyping, making application of EEC criteria difficult and only possible only in 15% of our patients. Within this subgroup, biopsies could be avoided in 83.3%, and 16.7% of patients with potential CD were misdiagnosed. Insufficient studies and incorrect interpretation of EEC contributed to incomplete assessment in 52/130 (40%) patients. The Chilean public health system is likely representative of several others present in developing and developed countries. (C) 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Compliance With Fecal Calprotectin Testing in Pediatric Inflammatory Bowel Disease Patients.

Fecal calprotectin (FC) is a highly sensitive biomarker for inflammatory bowel diseases (IBDs). Utilization of this assay has been steadily increasing. However, adherence levels for FC have yet to be examined in the pediatric IBD setting. We analyzed 100 consecutive patients diagnosed with IBD between 2014 and 2015 at Texas Children's Hospital. Fifty-six percent of patients were male and median age at diagnosis was 13.7 years. Following diagnosis of IBD, 84 patients had a minimum of one FC requested, and 95.2% of these patients completed the test at least once. An average of two FCs per patient were ordered each year, and the overall compliance was 76.6%. Patients who completed the initial testing with a minimum of three consecutive tests were more likely to remain compliant than those who failed to perform the first lab (p

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Premature Infants have Lower Gastric Digestion Capacity for Human Milk Proteins than Term Infants.

Objectives: Whether premature infants have lower gastric protein digestive capacity than term infants and the extent to which human milk proteases contribute to overall gastric digestion are unknown and were investigated in this study. Methods: Human milk and infant gastric samples were collected from 16 preterm (24-32 wk gestational age (GA)) and 6 term (38-40 wk GA) mother-infant pairs within a range of 5-42 days postnatal age. For each pair, an aliquot of human milk was adjusted to pH 4.5 and incubated for 2 h at 37 [degrees]C to simulate the gastric conditions without pepsin (milkinc). Their gastric protein digestion capacity was measured as proteolysis (free N-terminals) and protease activities. Two-way ANOVA followed by Tukey's post hoc test were applied to compare measurements between preterm and term infants as well as among human milk, milkinc and gastric samples. Results: Measurements of gastric protein digestion were significantly lower in preterm infants than term infants. Overall milk protease activity did not differ between human milk samples from term- and preterm-delivering mothers. As protease activity did not increase with simulated gastric incubation, milk proteases likely contributed minimally to gastric digestion. Conclusions: Preterm infants have lower gastric protein digestion capacity than term infants, which could impair nutrient acquisition. Human milk proteases contribute minimally to overall gastric digestion. The limited activity of milk proteases suggests that these enzymes cannot compensate for the premature infant's overall lower gastric protein digestion. (C) 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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The Changing Face of Pediatric Ulcerative Colitis: A Population-based Cohort Study.

Objectives: The aims of this retrospective study were to describe ulcerative colitis (UC) phenotype at diagnosis and follow-up and to identify possible predictors of severe disease course. Methods: This was a retrospective, single-center study. We reviewed the charts of patients with UC diagnosed between 2 and 18 years at our referral center from January 2007 to January 2016. Laboratory and clinical features at diagnosis, such as disease extent, atypical phenotypes, extraintestinal manifestations, and therapies, and pattern changes during the follow-up, including relapse rate, disease extension, and the cumulative risk for colectomy were collected. Results: One hundred eleven patients were identified. Atypical phenotypes were identified at diagnosis in 55 out of 111 patients (49.5%). Extraintestinal manifestations were detected in 16 out of 111 (14.4%) at the diagnosis. During the follow-up 60 out of 111 (54%) patients needed to start azathioprine, 9 out of 111 (8.1%) patients started biologic therapy and 10 out of 111 (patients underwent surgery, resulting in a cumulative risk of 8% at 5 years and 16% at 10 years. Steroid refractoriness (hazard ratio: 13.9) and starting of biologic therapy (hazard ratio: 25.3) represented the best predictors for surgery. The cumulative probability of first relapse was 47% at 6 months and 63% at 1 year. Disease extension was reported in 21 out of 70 patients (30%). Conclusion: Pediatric UC is associated with a severe phenotype and a high percentage of atypical features. Surgery rate seems to be decreased from early reports. (C) 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Shortened 8 Weeks Course of Dual Sofosbuvir/Daclatasvir Therapy in Adolescent Patients, with Chronic Hepatitis C Infection.

Recently, sofosbuvir and the fixed dose combination of sofosbuvir/ ledipasvir were approved for the treatment of chronic hepatitis C virus infection (HCV) in adolescents, 12 years old and above or weighing at least 35 kilograms. Here we present the results of a pilot single cohort of 10 consecutive adolescent patients with chronic HCV and treated with dual sofosbuvir/daclatasvir (SOF/DCV) therapy for a response-tailored duration of 8 weeks for those who achieved very rapid virologic response (vRVR) and 12 weeks for those who did not. All patients achieved vRVR at week 2 and completed the shortened 8 weeks course. All patients (10/10 (100% (CI: 72.25-100%)) achieved sustained virologic response at week 12 post-treatment (SVR12) with good tolerability and no serious adverse events. This data could provide support to our suggested response-tailored protocol of dual therapy with SOF/DCV in adolescents particularly for shortened duration in those who achieved vRVR. Further larger randomized controlled studies are recommended. (C) 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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A Pilot Study Measuring The Novel Satiety Hormone, Pro-Uroguanylin, In Adolescents With And Without Obesity.

Objective: Disruption of satiety signaling may lead to increased caloric intake and obesity. Uroguanylin, the intestinal hormone, travels as a precursor to the central nervous system where it activates guanylyl cyclase C (GUCY2C) and stimulates pro-satiety neurons. Rodent studies have demonstrated that (1) GUCY2C-knockout mice over-eat and have increased weight gain vs. wild-type mice; and (2) hyper-caloric obesity diminishes uroguanylin expression. We measured circulating plasma pro-uroguanylin, along with other gastrointestinal peptides and inflammatory markers, in human adolescents with and without obesity, as a pilot study. We hypothesized that adolescents with obesity would have less circulating pro-uroguanylin than adolescents without obesity have. Methods: We recruited 24 adolescents (age 14-17) with and without obesity (BMI >95% or BMI

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Announcing the 1st Annual NY Tactical EMS Expo and Training Symposium

MELVILLE, N.Y. — The 1st Annual NY Tactical EMS Expo is coming to Long Island January 6th and 7th, 2018 at the Huntington Hilton Expo Center in Melville, NY. The expo will feature 2 events under 1 roof bringing together the best training and products in the fields of EMS, Fire and Law Enforcement. There is 10,000 square feet of vendors, exhibits and public safety trade show featuring products ...

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Indian EMS providers to use motorcycles for quick response

The bikes will be introduced on a probationary basis to alleviate slow response times in congested areas of New Delhi

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Revisiting interhemispheric imbalance in chronic stroke: A tDCS study

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Publication date: January 2018
Source:Clinical Neurophysiology, Volume 129, Issue 1
Author(s): Alana B. McCambridge, James W. Stinear, Winston D. Byblow
ObjectiveChronic stroke patients with moderate-severe motor impairment may have an increased reliance on contralesional vs ipsilesional motor areas to control the paretic arm. We hypothesised that increasing contralesional excitability with anodal transcranial direct current stimulation (a-tDCS) would benefit motor performance in patients with moderate-severe impairment.MethodsTen patients with motor impairment at the chronic stage after stroke received a-tDCS, cathodal (c-tDCS) and sham with the target electrode over contralesional motor cortex (M1). Motor performance was quantified from the circularity and size of planar movements made with the paretic arm. Contralateral and ipsilateral corticospinal excitability was inferred using transcranial magnetic stimulation. Corticospinal tract integrity and basal GABA concentration were assessed with magnetic resonance imaging and spectroscopy.ResultsAnodal tDCS increased contralesional corticomotor excitability evident from motor evoked potentials in both wrist extensors (both P<0.043). Cathodal tDCS did not affect corticomotor excitability (P>0.37). The effect of tDCS on motor performance with the paretic limb was negatively associated with ipsilesional GABA concentration after c-tDCS (P=0.001).ConclusionsFurther investigation of noninvasive brain stimulation protocols that facilitate contralesional M1 is warranted.SignificanceThe inter-hemispheric imbalance model of stroke recovery may not apply to patients with more severe impairment.



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Muscle Strength Influences Pressor Responses to Static Handgrip in Men and Women.

Purpose: Whether differences in absolute muscle strength impact blood pressure (BP) responses to relative intensity static exercise remains controversial but could contribute to known sex-based differences and influence the interpretation of cross-sectional data. Methods: One hundred thirty-two healthy participants (66 men and 66 women, age: 22+/-3yrs) underwent continuous seated measurements of BP (Finometer) and heart rate (electrocardiography) during baseline rest and two minutes of static handgrip (30% maximal voluntary contraction [MVC]). BP and heart rate responses were quantified in 30-second epochs during exercise and compared between men and women with and without statistical adjustment (ANCOVA) for differences in baseline BP (or heart rate), forearm girth, and handgrip MVC. Within each sex, BP and heart rate responses were compared also between tertiles of handgrip MVC (n=22 per group). Results: Men had larger systolic, diastolic, and mean arterial pressure responses during static handgrip than women (interaction term, All P0.35). In men, BP responses were smaller within the lowest tertile of handgrip MVC (interaction term, All P

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Adapted Sojourn Models to Estimate Activity Intensity in Youth: A Suite of Tools.

The challenges of using physical activity data from accelerometers have been compounded with the recent focus on wrist-worn monitors and raw acceleration (as opposed to activity counts). PURPOSE: This study developed and systematically evaluated a suite of new accelerometer processing models for youth. METHODS: Four adaptations of the Sojourn method were developed using data from a laboratory-based experiment in which youth (N = 54) performed structured activity routines. The adaptations corresponded to all possible pairings of hip or wrist attachment with activity counts (AC) or raw acceleration (RA), and they estimated time in sedentary behavior, light activity, and moderate-to-vigorous physical activity (MVPA). Criterion validity was assessed using direct observation in an independent free-living sample (N = 27). Monitors were worn on both wrists to evaluate the impact of handedness on accuracy, and status quo methods for each configuration were also evaluated as benchmarks for comparison. Tests of classification accuracy (percent accuracy, kappa statistics, and sensitivity and specificity) were used to summarize utility. RESULTS: In the development sample, percent accuracy ranged from 68.5% (wrist-worn AC, [kappa] = 0.42) to 71.6% (hip-worn RA, [kappa] = 0.50). Accuracy was lower in the free-living evaluation, with values ranging from 50.9% (hip-worn RA, [kappa] = 0.27) to 58.5% (hip-worn AC, [kappa] = 0.38). Collectively, the suite predicted MVPA well, with the models averaging 97.0% sensitivity and 67.8% specificity. However, in terms of overall accuracy, the new models performed similarly to the status quo methods. There were no meaningful differences in performance at either wrist. CONCLUSION: The new models offered minimal improvements over existing methods, but a major advantage is that further tuning of the models is possible with continued research. (C) 2017 American College of Sports Medicine

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Severe energy deficit upregulates leptin receptors, leptin signaling, and PTP1B in human skeletal muscle

In obesity, leptin receptors (OBR) and leptin signaling in skeletal muscle are downregulated. To determine whether OBR and leptin signaling are upregulated with a severe energy deficit, 15 overweight men were assessed before the intervention (PRE), after 4 days of caloric restriction (3.2 kcal·kg body wt–1·day–1) in combination with prolonged exercise (CRE; 8 h walking + 45 min single-arm cranking/day) to induce an energy deficit of ~5,500 kcal/day, and following 3 days of control diet (isoenergetic) and reduced exercise (CD). During CRE, the diet consisted solely of whey protein (n = 8) or sucrose (n = 7; 0.8 g·kg body wt–1·day–1). Muscle biopsies were obtained from the exercised and the nonexercised deltoid muscles and from the vastus lateralis. From PRE to CRE, serum glucose, insulin, and leptin were reduced. OBR expression was augmented in all examined muscles associated with increased maximal fat oxidation. Compared with PRE, after CD, phospho-Tyr1141OBR, phospho-Tyr985OBR, JAK2, and phospho-Tyr1007/1008JAK2 protein expression were increased in all muscles, whereas STAT3 and phospho-Tyr705STAT3 were increased only in the arms. The expression of protein tyrosine phosphatase 1B (PTP1B) in skeletal muscle was increased by 18 and 45% after CRE and CD, respectively (P < 0.05). Suppressor of cytokine signaling 3 (SOCS3) tended to increase in the legs and decrease in the arm muscles (ANOVA interaction: P < 0.05). Myosin heavy chain I isoform was associated with OBR protein expression (r = –0.75), phospho-Tyr985OBR (r = 0.88), and phospho-Tyr705STAT3/STAT3 (r = 0.74). In summary, despite increased PTP1B expression, skeletal muscle OBR and signaling are upregulated by a severe energy deficit with greater response in the arm than in the legs likely due to SOCS3 upregulation in the leg muscles.

NEW & NOTEWORTHY This study shows that the skeletal muscle leptin receptors and their corresponding signaling cascade are upregulated in response to a severe energy deficit, contributing to increase maximal fat oxidation. The responses are more prominent in the arm muscles than in the legs but partly blunted by whey protein ingestion and high volume of exercise. This occurs despite an increase of protein tyrosine phosphatase 1B protein expression, a known inhibitor of insulin and leptin signaling.



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Walking economy is predictably determined by speed, grade, and gravitational load

The metabolic energy that human walking requires can vary by more than 10-fold, depending on the speed, surface gradient, and load carried. Although the mechanical factors determining economy are generally considered to be numerous and complex, we tested a minimum mechanics hypothesis that only three variables are needed for broad, accurate prediction: speed, surface grade, and total gravitational load. We first measured steady-state rates of oxygen uptake in 20 healthy adult subjects during unloaded treadmill trials from 0.4 to 1.6 m/s on six gradients: –6, –3, 0, 3, 6, and 9°. Next, we tested a second set of 20 subjects under three torso-loading conditions (no-load, +18, and +31% body weight) at speeds from 0.6 to 1.4 m/s on the same six gradients. Metabolic rates spanned a 14-fold range from supine rest to the greatest single-trial walking mean (3.1 ± 0.1 to 43.3 ± 0.5 ml O2·kg-body–1·min–1, respectively). As theorized, the walking portion (Vo2-walk = Vo2-gross – Vo2-supine-rest) of the body's gross metabolic rate increased in direct proportion to load and largely in accordance with support force requirements across both speed and grade. Consequently, a single minimum-mechanics equation was derived from the data of 10 unloaded-condition subjects to predict the pooled mass-specific economy (Vo2-gross, ml O2·kg-body + load–1·min–1) of all the remaining loaded and unloaded trials combined (n = 1,412 trials from 90 speed/grade/load conditions). The accuracy of prediction achieved (r2 = 0.99, SEE = 1.06 ml O2·kg–1·min–1) leads us to conclude that human walking economy is predictably determined by the minimum mechanical requirements present across a broad range of conditions.

NEW & NOTEWORTHY Introduced is a "minimum mechanics" model that predicts human walking economy across a broad range of conditions from only three variables: speed, surface grade, and body-plus-load mass. The derivation/validation data set includes steady-state loaded and unloaded walking trials (n = 3,414) that span a fourfold range of walking speeds on each of six different surface gradients (–6 to +9°). The accuracy of our minimum mechanics model (r2 = 0.99; SEE = 1.06 ml O2·kg–1·min–1) appreciably exceeds that of currently used standards.



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Acute effects of long-acting bronchodilators on small airways detected in COPD patients by single-breath N2 test and lung P-V curve

Small airways represent the key factor of chronic obstructive pulmonary disease (COPD) pathophysiology. The effect of different classes of bronchodilators on small airways is still poorly understood and difficult to assess. Hence the acute effects of tiotropium (18 µg) and indacaterol (150 µg) on closing volume (CV) and ventilation inhomogeneity were investigated and compared in 51 stable patients (aged 70 ± 7 yr, mean ± SD; 82% men) with moderate to very severe COPD. Patients underwent body plethysmography, arterial blood gas analysis, tidal expiratory flow limitation (EFL), dyspnea assessment, and simultaneous recording of single-breath N2 test and transpulmonary pressure-volume curve (PL-V), before and 1 h after drug administration. The effects produced by indacaterol on each variable did not differ from those caused by tiotropium, independent of the severity of disease, assessed according to the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) scale and the presence of EFL. Bronchodilators significantly decreased the slope of phase III and CV (–5 ± 4 and –2.5 ± 2.1%, respectively, both P < 0.001), with an increase in both slope and height of phase IV and of the anatomical dead space. Arterial oxygen pressure and saturation significantly improved (3 ± 3 mmHg and 2 ± 2%, respectively, both P < 0.001); their changes negatively correlated with those of phase III slope (r = –0.659 and r = –0.454, respectively, both P < 0.01). The vital capacity (VC) increased substantially, but the PL-V/VC curve above CV was unaffected. In conclusion, bronchodilators reduce the heterogeneity of peripheral airway mechanical properties and the extent of their closure, with minor effects on critical closing pressure. This should lessen the risk of small-airway damage and positively affect gas exchange.

NEW & NOTEWORTHY This is the first study investigating in stable chronic obstructive pulmonary disease patients the acute effects of two long-acting bronchodilators, a β-agonist and a muscarinic antagonist, on peripheral airways using simultaneous lung pressure-volume curve and single-breath N2 test. By lessening airway mechanical property heterogeneity, both drugs similarly reduced ventilation inhomogeneity and extent of small-airway closure, as indicated by the decrease of phase III slope, increased oxygen saturation, and fall of closing volume, often below expiratory reserve volume.



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Short-term arrival strategies for endurance exercise performance at moderate altitude

For sea level-based endurance athletes who compete at moderate and high altitudes, many are not logistically able to arrive at altitude weeks before the event to fully acclimatize. For those who can only arrive at altitude the night before competition, we asked if there is a physiological and performance advantage in reducing altitude exposure time to 2 h before competition. On three separate visits, 10 cyclists completed overnight laboratory exposures of: 1) a 14-h exposure to normobaric hypoxia (16.2% O2, simulating 2,500 m; 14H), 2) a 12-h exposure to normoxia, then a 2-h hypoxic exposure (2H), and 3) a 14-h exposure to normoxia (CON). Immediately following each exposure, subjects completed a 20-km cycle ergometry time trial in normoxia (CON) or 16.2% O2 (14H and 2H). Measures of plasma volume changes, sleep quality, ventilatory acclimatization, perceived exertion, oxygen uptake, and 20-km time were collected. No significant differences were observed in performance measures or perceived exertion between hypoxic trials. Plasma volume loss was significantly greater during 14H than 2H and CON. No differences in ventilatory acclimatization or sleep quality were observed between trials. Although some divergent 20-km performance responses were observed between 14H and 2H, they were not explained by the physiological measures completed. The data suggest that endurance athletes who are logistically restricted from arriving at altitude more than the evening before competition would not gain an advantage by delaying their arrival until a few hours before the competition, although unique individual responses may ultimately influence optimal arrival strategy.

NEW & NOTEWORTHY For athletes who cannot arrive at altitude multiple days before an endurance competition to properly acclimatize, this study asked if shortening hypoxic exposure time to 2 h before a competition was more advantageous than arrival at altitude the evening before competition. Our data suggest that athletes who cannot arrive at altitude with adequate time for complete acclimatization can choose the short-term arrival strategy that best fits with the logistics of their travel.



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Drowning in a river with an average depth of 3 ft: interpreting athletic performance gains



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Safety Outcomes Following Spine and Cranial Neurosurgery: Evidence From the National Surgical Quality Improvement Program.

Background: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) was used to establish predictors for 30-day postoperative complications following spine and cranial neurosurgery. Materials and Methods: The ACS-NSQIP participant use files were queried for neurosurgical cases between 2005 and 2015. Prevalence of postoperative complications following neurosurgery was determined. Nested multivariable logistic regression analysis was used to identify demographic, comorbidity, and perioperative characteristics associated with any complication and mortality for spine and cranial surgery. Results: There were 175,313 neurosurgical cases (137,029 spine, 38,284 cranial) identified. A total of 23,723 (13.5%) patients developed a complication and 2588 (1.5%) patients died. Compared with spine surgery, cranial surgery had higher likelihood of any complication (22.2% vs. 11.1%; P

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Phenytoin-induced Excessive Sedation During Awake Craniotomy: An Unusual Observation.

No abstract available

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NY hospitals testing 'ambient' ambulance sirens

EMS Supervisor Bob Levy said the hospitals are trying the two-toned, European sirens in an attempt to alleviate noise complaints

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Selected Literature Watch

Journal of Caffeine Research , Vol. 0, No. 0.


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Esophageal motility disorders: new perspectives from high-resolution manometry and histopathology

Abstract

High-resolution manometry (HRM) and peroral endoscopic myotomy (POEM) have contributed significantly to the field of esophageal motility disorders in recent years. The development of HRM has categorized various esophageal motility disorders with a focus on a diverse range of manometric anomalies. Additionally, the Chicago classification criteria is widely used for manometric diagnosis. Moreover, POEM was introduced as a minimally invasive radical therapy for achalasia and shows promise for other spastic esophageal motility disorders as well. POEM has also enabled a transluminal endoscopic approach for determining the histology of the esophageal muscle layer, which is expected to assist in elucidating the etiology of disorders associated with esophageal motility. The purpose of this review is to update the diagnosis, pathology, and treatment of esophageal motility disorders, with a focus on the recent advances in this field.



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Selected Literature Watch

Journal of Caffeine Research , Vol. 0, No. 0.


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Ecotracer: analyzing concentration of contaminants and radioisotopes in an aquatic spatial-dynamic food web model

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Publication date: January 2018
Source:Journal of Environmental Radioactivity, Volume 181
Author(s): William J. Walters, Villy Christensen
Ecotracer is a tool in the Ecopath with Ecosim (EwE) software package used to simulate and analyze the transport of contaminants such as methylmercury or radiocesium through aquatic food webs. Ecotracer solves the contaminant dynamic equations simultaneously with the biomass dynamic equations in Ecosim/Ecospace. In this paper, we give a detailed description of the Ecotracer module and analyze the performance on two problems of differing complexity. Ecotracer was modified from previous versions to more accurately model contaminant excretion, and new numerical integration algorithms were implemented to increase accuracy and robustness. To test the mathematical robustness of the computational algorithm, Ecotracer was tested on a simple problem for which we know an analytical solution. These results demonstrated the effectiveness of the program numerics. A much more complex model, the release of the cesium radionuclide 137Cs from the Fukushima Dai-ichi nuclear accident, was also modeled and analyzed. A comparison of the Ecotracer results to sampled 137Cs measurements in the coastal ocean area around Fukushima show the promise of the tool but also highlight some important limitations.



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Fatigue reporting processes reduce ambulance crash risk

Great strides have been made in ambulance safety, design and operation, but significant risk still exists

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EMS Artwork: Take pride in what you do

We're always looking at ways to improve prehospital care to our patients

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Study suggests women less likely to get CPR from bystanders

Only 39 percent of women suffering cardiac arrest in a public place were given CPR versus 45 percent of men

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EMS Artwork: Take pride in what you do

I'm a proud Canadian and Alberta paramedic. The province I work in has very progressive protocols and we're always looking at ways to improve prehospital care to our patients. We recently put a specialized ambulance on the road that is equipped with a mobile CT scanner. The idea is that eventually street medics will be able to scan stroke patients for blockages and administer thrombolitic therapy ...

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Correction to: Efficacy and safety of glecaprevir/pibrentasvir in HCV-infected Japanese patients with prior DAA experience, severe renal impairment, or genotype 3 infection

Unfortunately, in the original publication of this article, the copyright line was incorrectly published in PDF as "© The Author(s) 2017" instead of "©The Author(s) 2017 This article is an open access publication" and also the CC-BY description was not included. The description should be as follows.



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Fecal Transplantation for Treatment of Clostridium Difficile Infection in Elderly and Debilitated Patients

Abstract

Background

Fecal microbiota transplantation (FMT) is a new technique recently introduced to treat recurrent Clostridium difficile infection (CDI). Little is known about the efficacy and risks of FMT in elderly and ill patients.

Aim

To investigate FMT efficacy in ill and elderly patients compared to conventional treatment.

Methods

The study comprised two groups of patients between 2012 and 2016 with recurrent CDI at two medical centers in Israel. The study group received FMT and the controls conventional therapy. The primary end points were CDI recurrence, length of hospitalization, and short-term survival.

Results

Thirty-four patients altogether, (21 females, mean age 82 years) participated, 11 received FMT and 23 controls. Demographics and clinical characteristics were similar between the two groups. Comorbidity indexes, i.e., Charlson index was high in both groups. In the FMT group, 10/11 (90%) patients showed clinical improvement 3 days after initiating treatment compared to 9/23 (39%) in the control group, p = 0.02. Survival at 2 months did not differ between the groups (FMT 54%, Control 50%, p = 0.816), but mean survival in the FMT group was higher than in the control (12 vs. 4 months, respectively, p = 0.015). Two significant adverse events from the FMT group included suspected aspirations, both occurring during gastroscopy route of administration.

Conclusions

FMT is effective for elderly and very ill patients. Safety is a concern, but is rare even in patients with much comorbidity. Colonoscopy may be the preferred route of FMT infusion.



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Impact of intramuscular administration of lipid-soluble and water-soluble vehicles into regenerating muscle at the distinct phases of skeletal muscle regeneration

Abstract

Interpretation on the effectiveness of potential substances to enhance skeletal muscle regeneration is difficult if an inappropriate vehicle is administered, since vehicle administration can directly enhance or suppress regenerative capacity. In the current study, intramuscular administration of lipid-soluble and water-soluble vehicles into regenerating muscle at the distinct phases of skeletal muscle regeneration (regenerative vs. remodeling) were investigated. Tested vehicles included lipid-soluble [olive oil, (0.1, 1, 5, and 40%) dimethyl sulfoxide (DMSO), and 40% propylene glycol (PG)] and water-soluble [0.9% NaCl, PBS, 0.1% ethanol, and distilled water]. Skeletal muscle regeneration was induced by 1.2% BaCl2 injection to the tibialis anterior muscle of 10-week-old C57BL/6 male mice. Histological features, skeletal muscle stem cell activity, regenerating muscle fiber formation, angiogenesis, extracellular matrix remodeling, and macrophage infiltration were examined. The results revealed repeated administration of 40% DMSO and 40% PG causes significant recurrent muscle injury, which is pronounced during the remodeling phase compared to the regenerative phase. These findings were supported by (1) massive infiltration of F4/80+ macrophages; (2) significant increase of skeletal muscle stem cell re-activation and nascent regenerating muscle fiber formation; (3) excess fibrous formation; and (4) decreased regenerating muscle fiber cross-sectional area. These deleterious effects were comparable to 2% trypsin (degenerative substance) administration and less pronounced with a single administration. Nevertheless, recurrent muscle injury was still presented with 5% DMSO administration but it can be alleviated when 0.1% DMSO was administered during the remodeling phase. In contrast, none of the tested vehicles enhanced regenerative capacity compared with IGF-1 administration. Altogether, intramuscular administration of vehicle containing high concentration of DMSO or PG could impair skeletal muscle regenerative capacity and potentially affect validation of the investigational substance.



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Case Report of Successful Medical Management of Progressive Gastric Band Penetration-to-Perforation After Band Insertion at Bariatric Surgery: Documentation by 12 Serial EGDs During 50 months of Observation



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Transcription: Putting R loops firmly on the map

Transcription: Putting R loops firmly on the map

Transcription: Putting R loops firmly on the map, Published online: 13 November 2017; doi:10.1038/nrg.2017.98



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Functional genomics: Shining a light on genetic screen strategies

Functional genomics: Shining a light on genetic screen strategies

Functional genomics: Shining a light on genetic screen strategies, Published online: 13 November 2017; doi:10.1038/nrg.2017.99



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Statistical and integrative system-level analysis of DNA methylation data

Statistical and integrative system-level analysis of DNA methylation data

Statistical and integrative system-level analysis of DNA methylation data, Published online: 13 November 2017; doi:10.1038/nrg.2017.86

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The wealth of DNA methylation data continues to grow rapidly, including from epigenome-wide association studies (EWAS). However, extracting meaningful biological and clinical information requires diverse computational approaches for data analysis. This Review discusses the range of statistical tools available, including for cell-type deconvolution, identification of important methylation data features, causation and system-level integration with other types of omic data.

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Towards a genomics-informed, real-time, global pathogen surveillance system

Towards a genomics-informed, real-time, global pathogen surveillance system

Towards a genomics-informed, real-time, global pathogen surveillance system, Published online: 13 November 2017; doi:10.1038/nrg.2017.88

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Next-generation sequencing has the potential to support public health surveillance systems to improve the early detection of emerging infectious diseases. This Review delineates the role of genomics in rapid outbreak response and the challenges that need to be tackled for genomics-informed pathogen surveillance to become a global reality.

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Effects of Caffeine Supplementation on Performance in Ball Games

Abstract

Although a large body of evidence exists documenting the ergogenic properties of caffeine, most studies have focused on endurance performance. However, findings from endurance sports cannot be generalized to performance in ball games where, apart from having a high level of endurance, successful athletic performances require a combination of physiological, technical and cognitive capabilities. The purpose of this review was to critically evaluate studies that have examined the effect of a single dose of caffeine in isolation on one or more of the following performance measures: total distance, sprint performance, agility, vertical jump performance and accuracy in ball games. Searches of three major databases resulted in 19 studies (invasion games: 13; net-barrier games: 6) that evaluated the acute effects of caffeine on human participants, provided the caffeine dose administered, and included a ball games specific task or simulated match. Improvements in sprint performance were observed in 8 of 10 studies (80%), and vertical jump in 7 of 8 studies (88%). Equivocal results were reported for distance covered, agility and accuracy. Minor side effects were reported in 4 of 19 studies reviewed. Pre-exercise caffeine ingestion between 3.0 and 6.0 mg/kg of body mass appears to be a safe ergogenic aid for athletes in ball games. However, the efficacy of caffeine varies depending on various factors, including, but not limited to, the nature of the game, physical status and caffeine habituation. More research is warranted to clarify the effects of caffeine on performance measures unique to ball games, such as agility and accuracy. It is essential that athletes, coaches and practitioners evaluate the risk-benefit ratio of caffeine ingestion strategies on an individual case-by-case basis.



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The Effects of Resistance Exercise Training on Anxiety: A Meta-Analysis and Meta-Regression Analysis of Randomized Controlled Trials

Abstract

Background

The salutary effects of resistance exercise training (RET) are well established, including increased strength and function; however, less is known regarding the effects of RET on mental health outcomes. Aerobic exercise has well-documented positive effects on anxiety, but a quantitative synthesis of RET effects on anxiety is needed.

Objectives

To estimate the population effect size for resistance exercise training (RET) effects on anxiety and to determine whether variables of logical, theoretical, and/or prior empirical relation to anxiety moderate the overall effect.

Methods

Thirty-one effects were derived from 16 articles published before February 2017, located using Google Scholar, MEDLINE, PsycINFO, PubMed, and Web of Science. Trials involved 922 participants (mean age = 43 ± 21 years, 68% female/32% male) and included both randomization to RET (n = 486) or a non-active control condition (n = 436), and a validated anxiety outcome measured at baseline, mid-, and/or post-intervention. Hedges' d effect sizes were computed and random effects models were used for all analyses. Meta-regression quantified the extent to which participant and trial characteristics moderated the mean effect.

Results

RET significantly reduced anxiety symptoms (Δ = 0.31, 95% CI 0.17–0.44; z = 4.43; p < 0.001). Significant heterogeneity was not indicated (Q T(30) = 40.5, p > 0.09; I 2 = 28.3%, 95% CI 10.17–42.81); sampling error accounted for 77.7% of observed variance. Larger effects were found among healthy participants (Δ = 0.50, 95% CI 0.22–0.78) compared to participants with a physical or mental illness (Δ = 0.19, 95% CI 0.06–0.31, z = 2.16, p < 0.04). Effect sizes did not significantly vary according to sex (β = −0.31), age (β = −0.10), control condition (β = 0.08), program length (β = 0.07), session duration (β = 0.08), frequency (β = −0.10), intensity (β = −0.18), anxiety recall time frame (β = 0.21), or whether strength significantly improved (β = 0.19) (all p ≥ 0.06).

Conclusions

RET significantly improves anxiety symptoms among both healthy participants and participants with a physical or mental illness. Improvements were not moderated by sex, or based on features of RET. Future trials should compare RET to other empirically-supported therapies for anxiety.



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Medicinal Foods for Functional GI Disorders

Abstract

Purpose of Review

Over the past 10 years, there has been a dramatic increase in basic and clinical research involving functional gastrointestinal disorders (FGIDs). New diagnostic and biomarker procedures are helping to identify physiologic disruptions associated with FGIDs on cellular and molecular levels. Simultaneously, clinicians are using new approaches to help manage patients with FGIDs. Among these, an important component of care has been the use of medical foods. These include probiotics, prebiotics, synbiotics, peppermint oil, caraway oil, curcumin, bovine immunoglobulin and many others.

Recent Findings

The putative effects of different medical foods make these therapies attractive for the management of FGIDs. These include effects on several pathophysiological mechanisms such as anti-inflammatory, smooth muscle relaxation, analgesia, mitigation of gut barrier dysfunction, and stimulation or inhibition of gastrointestinal receptors. Recent research has also demonstrated the efficacy of medical food products such as peppermint oil and serum-derived bovine immunoglobulin for the management of irritable bowel syndrome. Older data supports the probiotic VSL#3 and Bifidobacterium species. For functional dyspepsia, positive effects have been observed with the combination of caraway seed oil and peppermint oil as well as with STW-5, a botanical combination preparation, although robust RCTs are lacking.

Summary

With advancing knowledge regarding the pathogenesis of FGIDs, it is likely that the compounds available in the medical food category will increase dramatically, and they could play an important role in the management of several common and bothersome gastrointestinal conditions in the future.



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Correction to: Potential signaling pathways of acute endurance exercise-induced cardiac autophagy and mitophagy and its possible role in cardioprotection

Abstract

The article Potential signaling pathways of acute endurance exercise-induced cardiac autophagy and mitophagy and its possible role in cardioprotection, written by Youngil Lee.



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