Παρασκευή, 25 Ιανουαρίου 2019

Analysis of allele-specific expression of seven candidate genes involved in lipid metabolism in pig skeletal muscle and fat tissues reveals allelic imbalance of ACACA , LEP , SCD , and TNF

Abstract

Analysis of allele-specific expression may help to elucidate the genetic architecture of complex traits including fat deposition in pigs. Here, we used pyrosequencing to investigate the allele proportions of candidate genes (ACACA, ADIPOR1, FASN, LEP, ME1, SCD, and TNF) involved in regulation of lipid metabolism in two fat deposits (subcutaneous and visceral fat) and longissimus dorsi muscle of pigs representing Polish Large White, Polish Landrace, Duroc, and Pietrain breeds. We detected differential allelic expression of ACACA, LEP, SCD, and TNF in all tissues analyzed. To search for putative cis-regulatory elements involved in allele-specific expression, we quantified the methylation level within CpG islands located in 5′-flanking regions of ACACA and SCD. Comparison between samples showing markedly disproportionate allelic expression and control groups with similar levels of both alleles did not reveal significant differences. We also assessed the association of rs321308225 (c.*195C>A) an SNP located in the 3′UTR of ACACA with its allelic expression in Polish Landrace pigs, but it was not significant. We conclude that allelic imbalance occurs frequently in regard to genes involved in regulation of lipid deposition in pigs, and further studies are necessary to identify cis-regulatory elements affecting ACACA, LEP, SCD, and TNF expression in porcine fat tissues and skeletal muscle.



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Diversifying selection signatures among divergently selected subpopulations of Polish Red cattle

Abstract

Polish Red cattle is one of the few indigenous breeds of European red cattle which is characterized by several desired features, such as high disease resistance, good health, longevity, good fertility, and high nutritional value of milk. Currently, Polish Red cattle population is a subject of two independent breeding programs: (i) improvement program and (ii) genetic resources conservation program. The aim of the improvement program is the genetic progress in terms of milk production and body conformation traits, while the conservation program mainly focuses on protection of the genetic resources of Polish Red cattle and preservation of the existing, original gene pool. By the analysis of FST genetic distances across genome-wide SNP panel, we detected diversifying selection signatures among these two subpopulations and indicated (among others) the significance of DGAT1 and FGF2 genes for milk production traits in these cattle. We also found that among genes being presumably under selection in terms of milk production, there are genes responsible, for example, for mammary gland development (e.g., SOSTDC1, PYGO2, MED1, and CCND1) and immune system response (e.g., IL10RA, IL12B, and IL21). The most important finding of this study is that the most pronounced genetic differences between the analyzed populations were associated with β-defensin genes (e.g., DEFB1, DEFB4A, DEFB5, DEFB7, DEFB10, DEFB13, EBD, BNBD-6, and LAP) located within so-called bovine cluster D on BTA27. The β-defensins are expressed mainly in the mammary gland and are antimicrobial peptides against the Gram-negative and Gram-positive bacteria, viruses, and other unicellular parasites. This suggests that antimicrobial resistance of mammary gland is of high importance during selection towards increased milk production and that genes responsible for this process are selected together with increasing levels of productivity.



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High Prevalence of Antimicrobial Resistance in Gram-Negative Bacteria Isolated from Clinical Settings in Egypt: Recalling for Judicious Use of Conventional Antimicrobials in Developing Nations

Microbial Drug Resistance, Ahead of Print.


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Albumin-Bilirubin (ALBI) as an accurate and simple prognostic score for chronic hepatitis B-related liver cirrhosis

The Albumin–Bilirubin (ALBI) score was developed to predict the long-term prognosis of hepatocellular carcinoma patients. We aimed to investigate the performance of ALBI for predicting severity and long-term prognosis of chronic hepatitis B-related liver cirrhosis (CHB-LC).

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A crash course in sequencing for a microbiologist

Abstract

For the last 40 years, "Sanger sequencing" allowed to unveil crucial secrets of life. However, this method of sequencing has been time-consuming, laborious and remains expensive even today. Human Genome Project was a huge impulse to improve sequencing technologies, and unprecedented financial and human effort prompted the development of cheaper high-throughput technologies and strategies called next-generation sequencing (NGS) or whole genome sequencing (WGS). This review will discuss applications of high-throughput methods to study bacteria in a much broader context than simply their genomes. The major goal of next-generation sequencing for a microbiologist is not really resolving another circular genomic sequence. NGS started its infancy from basic structural and functional genomics, to mature into the molecular taxonomy, phylogenetic and advanced comparative genomics. Today, the use of NGS expended capabilities of diagnostic microbiology and epidemiology. The use of RNA sequencing techniques allows studying in detail the complex regulatory processes in the bacterial cells. Finally, NGS is a key technique to study the organization of the bacterial life—from complex communities to single cells. The major challenge in understanding genomic and transcriptomic data lies today in combining it with other sources of global data such as proteome and metabolome, which hopefully will lead to the reconstruction of regulatory networks within bacterial cells that allow communicating with the environment (signalome and interactome) and virtual cell reconstruction.



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The long and the short of it

The long and the short of it

The long and the short of it, Published online: 25 January 2019; doi:10.1038/s41576-019-0098-2

Two studies in Developmental Cell report the generation of mice with longer and shorter than normal tails, respectively, giving insight into developmental programmes and key genes involved in mouse tail development.

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Learning the language of splicing

Learning the language of splicing

Learning the language of splicing, Published online: 25 January 2019; doi:10.1038/s41576-019-0097-3

A new study uses deep learning to predict genetic variants that generate cryptic splice sites and to investigate the role of these non-coding cryptic splice mutations in rare genetic disorders.

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An Operable, Portable, and Disposable Ultrathin Endoscope for Evaluation of the Upper Gastrointestinal Tract

Abstract

Background and Aims

A prototype of a disposable endoscope (DE) with easy viewing of the esophagus has been developed. The aim of this study was to develop a new version of DE with improved functionality and to assess the feasibility of DE as a screening tool for upper gastrointestinal diseases compared with conventional endoscopes.

Methods

Diagnostic accuracy and maneuverability of DE were evaluated by comparing endoscopy using DE with conventional endoscopy. Different examiners performed DE endoscopy and conventional endoscopy in a randomized order, blinded to the results. Examiners were asked to respond to a questionnaire about ease of handling and observation using DE in preformed result sheets. Tolerability of DE was also evaluated. Non-sedated participants were asked to respond to a questionnaire about the convenience and satisfaction with DE endoscopy on a nine-point Likert scale.

Results

The overall ease of insertion and handling of DE was excellent. The new device enabled observation and evaluation of the entire esophagus with a good agreement between DE endoscopy and conventional endoscopy in terms of endoscopic diagnosis (Kappa value; hiatal hernia; 0.910, reflux esophagitis; 0.949, Barrett's esophagus, 1.000). Participants suggested that they were more comfortable with DE endoscopy than with conventional endoscopy with a lower symptom score (p = 0.030).

Conclusion

The new DE enabled easy observation of the entire esophagus owing to its improved maneuverability, and its diagnostic ability of esophageal diseases was comparable to that of conventional endoscopes. Non-sedated esophagoscopy with this disposable device potentially has widespread applications in outpatient clinics and areas without endoscopic facilities.



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Early Postoperative Anti-TNF Therapy Does Not Increase Complications Following Abdominal Surgery in Crohn’s Disease

Abstract

Background

The impact of postoperative anti-TNF therapy on infectious complications following Crohn's disease surgery remains controversial. Use of anti-TNF therapy 2–4 weeks postoperatively appears safe, but safety of use within 2 weeks is unknown.

Aims

We sought to evaluate the effect of anti-TNF therapy initiated within 2 weeks of abdominal surgery in patients with Crohn's disease.

Methods

We conducted a retrospective review of adult Crohn's disease patients undergoing abdominal surgery between 2004 and 2011. Infectious and non-infectious complications were compared between patients exposed to anti-TNF therapy within 2 weeks or between 2 and 4 weeks postoperatively and to those without exposure using chi-squared and regression analysis.

Results

Three hundred thirty-one abdominal surgeries were included; 241 were without anti-TNF exposure, 46 received postoperative anti-TNF within 2 weeks of surgery, and 44 received anti-TNF therapy 2–4 weeks after surgery. Patients who received anti-TNF therapy within 2 weeks of surgery, those initiated between 2 and 4 weeks of surgery, and those who did not receive anti-TNF therapy within 4 weeks of surgery had no significant difference in rates of infectious complications (22%, 32%, 33%, p = 0.332). Rates of non-infectious complications (4%, 9%, 14%, p = 0.143), mortality (0%, 0%, 3%, p = 0.105), hospital readmission (17%, 16%, 15%, p = 0.940), and reoperation (11%, 11%, 16%, p = 0.563) were also similar between groups.

Conclusions

Use of early anti-TNF therapy within 2 weeks or between 2 and 4 weeks following abdominal surgery did not increase risk of postoperative surgical infections in Crohn's patients.



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Laryngopharyngeal Reflux: Weak Acid and Weaker Correlations



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Safety of Cold Snare Polypectomy in Patients Receiving Treatment with Antithrombotic Agents

Abstract

Background

With the aging of the population and rising incidence of thromboembolic events, the clinical use of antithrombotic agents is also increasing. There are few reports yet on the management of antithrombotic agent use in patients undergoing cold snare polypectomy (CSP).

Aims

The aim of this study was to evaluate whether continued administration of antithrombotic agents in patients undergoing CSP would be associated with an increased rate of delayed post-polypectomy bleeding (DPPB).

Methods

A total of 1177 colorectal polyps in 501 patients were resected at Omori Red Cross Hospital between October 2017 and March 2018. The polyps were divided into two groups depending on whether the patients received antithrombotic agent treatment or not: the antithrombotic group (911 polyps) and the no-antithrombotic group (266 polyps).

Results

Among the 1177 polyp resections, there was no case of DPPB, including in the antithrombotic group. Immediate bleeding occurred in a total of 63 (5.4%) cases. Polyp location in the rectum (OR (95% CI) 2.64 (1.223–5.679); p = 0.013), polyp size ≥ 6 mm (OR (95% CI) 4.64 (2.719–7.933); p < 0.001), polypoid growth pattern (OR (95% CI) 2.78 (1.607–4.793); p < 0.001), and antithrombotic agent use (OR (95% CI) 2.98 (1.715–5.183); p < 0.001) were identified as significant risk factors of immediate bleeding.

Conclusions

Continued use of antithrombotic agents does not increase the risk of DPPB, even in those receiving multiple antithrombotic agents. Thus, it is safe to perform CSP even in multiple agent users. Prospective, randomized studies are necessary to confirm our results.



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Musculoskeletal Injuries Are Commonly Reported Among Gastroenterology Trainees: Results of a National Survey

Abstract

Background

Endoscopy-related musculoskeletal injuries are increasingly recognized among gastroenterologists. While injury rates and risk factors have been studied among practicing gastroenterologists, little is known about rates among trainees during fellowship.

Aims

This study analyzes the prevalence of endoscopy-related overuse injuries and risk factors for injuries among a national sample of gastroenterology (GI) fellows. We also surveyed GI fellowship program directors and fellows about perceptions of overuse injuries during GI training.

Methods

We distributed a 29-item electronic survey to GI fellows at accredited programs in the USA in April 2016. Survey items included demographic information, questions pertaining to injuries, and level of agreement on the importance of ergonomics training in GI fellowship. Additionally, we distributed a 7-item electronic survey to fellowship program directors evaluating perception of overuse injuries and prevention during fellowship training. Fisher's exact test determined factors associated with sustaining an injury.

Results

An estimated 1509 fellows received the survey. Eleven percent (n = 165) of gastroenterology fellows completed the survey. Twenty percent reported having a musculoskeletal injury. Female gender was the only factor associated with a higher rate of reported injury (p < 0.01). The most common injuries reported were thumb and other hand-related pain (n = 28 [64%]).

Conclusions

Musculoskeletal injuries may affect up to 20% of GI fellows. Female fellows more frequently report injuries and may be at particularly high risk which has not been found in previously reported surveys of practicing gastroenterologists. Standardized curricula on ergonomic considerations and injury prevention are needed to enhance GI fellowship training and reduce injury rates.



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Empagliflozin for the Treatment of Nonalcoholic Steatohepatitis in Patients with Type 2 Diabetes Mellitus

Abstract

Background and Aims

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of drugs that lower glucose by inducing renal glycosuria. We aimed to explore whether SGLT2 inhibitor added to the usual care for patients with type 2 diabetes mellitus (T2DM) and biopsy-proven nonalcoholic steatohepatitis (NASH) will benefit NASH histology.

Methods

In this investigator-initiated, single-arm, open-label, pilot study, nine biopsy-proven NASH patients with T2DM were given empagliflozin 25 mg daily for 24 weeks. Liver biopsy was repeated at the end of treatment. The histological outcomes were compared with the placebo group of a previous 48-week clinical trial.

Results

There was a significant reduction in body mass index (median change, Δ = −0.7 kg per m2, p = 0.011), waist circumference (Δ = −3 cm, p = 0.033), systolic blood pressure (Δ = −9 mmHg, p = 0.024), diastolic blood pressure (Δ = −6 mmHg, p = 0.033), fasting blood glucose (Δ = −1.7 mmol/L, p = 0.008), total cholesterol (Δ = −0.5 mmol/L, p = 0.011), gamma glutamyl transpeptidase (Δ = −19 U/L, p = 0.013), volumetric liver fat fraction (Δ = −7.8%, p = 0.017), steatosis (Δ = −1, p = 0.014), ballooning (Δ = −1, p = 0.034), and fibrosis (Δ = 0, p = 0.046). All histological components either remained unchanged or improved, except in one patient who had worsening ballooning. Empagliflozin resulted in significantly greater improvements in steatosis (67% vs. 26%, p = 0.025), ballooning (78% vs. 34%, p = 0.024), and fibrosis (44% vs. 6%, p = 0.008) compared with historical placebo.

Conclusion

This pilot study provides primary histological evidence that empagliflozin may be useful for the treatment of NASH. This preliminary finding should prompt larger clinical trials to assess the effectiveness of empagliflozin and other SGLT2 inhibitors for the treatment of NASH in T2DM patients.

Trial registry number ClincialTrials.gov number, NCT02964715.



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Recommendations on the Diagnosis and Initial Management of Acute Variceal Bleeding and Hepatorenal Syndrome in Patients with Cirrhosis

Abstract

Cirrhosis is a serious and life-threatening condition which imposes a significant socioeconomic burden on affected individuals and healthcare systems. Cirrhosis can result in portal hypertension, which may lead to major complications, including acute variceal bleeding and hepatorenal syndrome. Without prompt treatment, these complications may be life-threatening. Over the past 2 decades, new treatment modalities and treatment strategies have been introduced, which have improved patients' prognosis, but the initial management of these severe complications continues to present a challenge. The present recommendations aim to increase clinicians' knowledge on the importance of early diagnosis and treatment, and to provide evidence-based management strategies to potentially, further improve patient outcomes. Special attention was given to the role of terlipressin. A comprehensive non-systematic literature search was undertaken to evaluate the evidence for the diagnosis and initial management of acute variceal bleeding and hepatorenal syndrome in patients with cirrhosis. Recommendations on the diagnosis and initial management of acute variceal bleeding and hepatorenal syndrome in patients with cirrhosis have been developed based on the best available evidence and the expert opinion of the consensus panel following a comprehensive review of the available clinical data. Prompt identification and timely treatment of acute variceal bleeding and hepatorenal syndrome are essential to reduce the burden.



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Work Stress and Satisfaction with Leadership Among Nurses Encountering Patient Aggression in Psychiatric Care: A Cross-Sectional Survey Study

Abstract

We examined the associations between work stress (job strain, effort-reward imbalance), perceived job insecurity, workplace social capital, satisfaction with leadership and working hours in relation to the likelihood of encountering patient aggression (overall exposure, assaults on ward property, mental abuse, physical assaults). We conducted a cross-sectional survey for nurses (N = 923) in 84 psychiatric units. Both work stress indicators were associated higher odds for different types of patient aggression. Poorer satisfaction with leadership was associated with higher odds for overall exposure to patient aggression. These findings were robust to adjustment for several nurse and work characteristics, and unit size.



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A new analysis workflow for discrimination of nuclear grade graphite using laser-induced breakdown spectroscopy

Publication date: April 2019

Source: Journal of Environmental Radioactivity, Volumes 199–200

Author(s): John P.O. Horsfall, Divyesh Trivedi, Nick T. Smith, Philip A. Martin, Paul Coffey, Stella Tournier, Anthony Banford, Lin Li, David Whitehead, Adam Lang, Gareth T.W. Law

Abstract

Stand-off, in-situ, laser induced breakdown spectroscopy (LIBS) offers a rapid, safe, and cost-effective method for discrimination of radioactive waste materials arising during the operation of nuclear plants and from decommissioning activities. Characterisation of waste materials is a critical activity in understanding the nature of the waste, ensuring hazardous material is managed safely and that waste can be segregated for reuse, recycle or sentenced for appropriate disposal. Characterisation of materials, often in hostile environments, requires the ability to remotely differentiate between materials in terms of their chemical composition and radioactivity.

This proposition was tested using a case study on nuclear grade graphite. Graphite has been used extensively as a moderator material in many nuclear reactors. Internationally, over 250,000 tons of various nuclear-grade graphite, and graphite-bearing, materials exist. These are a major issue for nuclear decommissioning and radioactive waste management, due to the long half-lives of the associated 14C and 36Cl isotopes. LIBS offers a method for discrimination of nuclear grade graphites and other carbon and non-carbon-bearing wastes. This paper describes the development of a workflow method, including LIBS measurement analysis, for the discrimination of pre-irradiated nuclear 'Pile Grade A' (PGA) graphite moderator rod and domestic lumpwood charcoal, which act as surrogates for nuclear grade graphite and other carbon-bearing wastes. A new analysis workflow comprising the examination of spectral characteristics, multivariate analysis and molecular isotopic spectroscopy is proposed to enable rapid segregation of graphite from a heterogeneous waste stream. Enhanced characterisation techniques have the potential to significantly reduce the cost of decommissioning large parts of legacy nuclear generation plants.



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Radon removal trap design and coefficient testing for the development of an effective radioxenon sampling, separation and measurement system

Publication date: April 2019

Source: Journal of Environmental Radioactivity, Volumes 199–200

Author(s): Chongyang Zhou, Guoqing Zhou, Shujuan Feng, Xinhua Zhao, Dingwei Huang, Zining Tian, Xiaolong Yu, Ziwei Cheng

Abstract

To monitor low-level radioxenon isotopes activity concentrations in the bulk gases, a radioxenon sampling, separation and measurement system has been developed. The xenon enrichment factor of this system is more than 105 after the separation of impurities, including N2, O2, CO2and H2O, as well as radon and its progenies, such as 214Pb and 214Bi. Since radon and its progenies interfere with radioxenon measurement, they have to be removed before radioxenon counting. To separate radon from xenon, different dynamic adsorption coefficients of xenon and radon are used to design small radon removal trap to retain radon after eluting xenon, and the ratio between radon and xenon dynamic adsorption coefficient gives the adsorbent weight relationship between the xenon adsorption trap and its related radon removal trap. To test the effectiveness of radon removal, the relative measuring method is used by measuring γ-rays energies of radon progenies in canister filling with either the measuring sample prepared by the system or the original gas. The results show that the radon removal coefficient and the stable xenon recovery, which are two important parameters in the radioxenon system, are at the order of 10−6 and >70% respectively. These meet the specifications proposed by the Comprehensive Nuclear-Test-Ban Treaty Organization.



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Learning the language of splicing



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The long and the short of it



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Involuntary sensory enhancement of gain- and loss-associated tones: A general relevance principle

Publication date: Available online 25 January 2019

Source: International Journal of Psychophysiology

Author(s): Timea Folyi, Dirk Wentura

Abstract

In a recent event-related potential (ERP) study (Folyi et al., 2016), we have demonstrated that sensory processing of task-irrelevant tones is enhanced when they were previously associated with positive or negative (by the means of monetary gains and losses, respectively) affective meaning relative to tones with neutral meaning, as indexed by the enhancement of the auditory N1-amplitude. In the present study, (1) in line with the hypothesis of affective counter-regulation, we investigated whether positive versus negative tones can receive differential attentional enhancement, depending on motivational context (Experiment 1); and (2) whether the early facilitation of positive and negative tones can operate strictly outside of the focus of voluntary attention (Experiment 2). In Experiment 1, we replicated the basic N1 valence effect, but found no moderation by motivational context. In Experiment 2, we found a small valence effect on the N1. By combining data from the three experiments (i.e., our previous experiment and the present ones; N = 72), we found a clear enhancement of N1-amplitudes for valenced tones without moderation by experiment. This pattern of results suggests comparable early attentional enhancement of valenced tones in general: (a) despite different level of concurrent task-relevant attentional and motivational demands in these experiments; and (b) without prioritizing one valence category over another, supporting our claim that the general relevance of the tones with high motivational value that governs early attentional facilitation.



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Personalizing Neuromodulation

Publication date: Available online 24 January 2019

Source: International Journal of Psychophysiology

Author(s): John D. Medaglia, Brian Erickson, Jared Zimmerman, Apoorva Kelkar

Abstract

In the era of "big data", we are gaining rich person-specific information about neuroanatomy, neural function, and cognitive functions. However, the optimal ways to create precise approaches to optimize individual function in healthy and disease are unclear. Multimodal analysis and modeling approaches that combine anatomical networks, functional signals, and cognitive neuroscience in single subjects can guide neuromodulation. Our progress could be improved by progressing from statistical fits to mechanistic models. Using transcranial magnetic stimulation as an example, we discuss how integrating methods with a focus on mechanisms could improve our predictions TMS effects within individuals, refine our models of health and disease, and improve our treatments.



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A case of early‐onset epileptic encephalopathy with a homozygous TBC1D24 variant caused by uniparental isodisomy

TBC1D24‐related disorders are rare neurodevelopmental disorders that show a broad range of neuropsychiatric deficits and are mostly inherited in an autosomal recessive manner. Here we describe a case with early‐onset epileptic encephalopathy, in whom exome sequencing detected a novel pathogenic homozygous c.442G>A, p.(Glu148Lys) variant in TBC1D24. She showed severe developmental delay, congenital sensorineural hearing loss and seizures, but the combination of a high dose phenobarbital and potassium bromide was very effective for the seizures. Sanger sequencing revealed that her mother was a heterozygous carrier of the TBC1D24 variant, but her father showed only wild‐type alleles. Homozygosity mapping analysis using exome data showed loss of the heterozygosity region at 16p13.3–p13.13 encompassing TBC1D24. Genotyping analysis using rare variants within loss of the heterozygosity region indicated that the patient has a homozygous haplotype inherited from her mother, indicating maternal segmental uniparental isodisomy (UPiD). These data clearly show that exome sequencing is a powerful tool to perform comprehensive genetic analysis.



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Preteratment with β‐glucan attenuates isoproterenol‐ induced myocardial injury in rats

New Findings

What is the central question of this study?

The present study has been designed to assess whether pretreatment with β glucan could exert any protective action against ISO‐induced myocardial injury in rats.

What is the main finding and its importance?

β‐glucan pretreatment could reduce myocardial injury by restoring cardiac biomarkers, antioxidant status, apoptosis and histopathological changes. Therefore, β‐glucan may have the potential to be used in the prevention and/or treatment of myocardial infarction.

Abstract

This study was designed to investigate the cardioprotective effect of pretreatment with β‐glucan, the glucose polymer derived from the yeast Saccharomyces cerevisiae, against isoproterenol (ISO)‐induced myocardial injury in rats by studying the biochemical cardiac markers, antioxidant parameters, apoptosis, electrocardiographic and histopathological changes. Male Sprague Dawley rats were randomly divided into four groups, namely control, β‐glucan, isoproterenol and β‐glucan + isoproterenol treated group. β‐glucan treatment group received β‐glucan (50 mg kg−1/day, orally) for 10 days. Myocardial injury was induced by ISO administration (100 mg kg−1, s.c.) twice at an interval of 24 h on 9th and 10th day. ISO administration resulted in a marked increase in heart rate, ST segment elevation, myocardial malondialdehyde content, cardiac marker levels (lactate dehydrogenase, creatine kinase‐MB and high‐sensitivity cardiac troponin T) and apoptotic index, and a significant decrease in R wave amplitude and myocardial superoxide dismutase, catalase and glutathione peroxidase activities. In addition, apoptosis, congestion, necrosis, inflammatory cells infiltration and myofibrillar disorganization were histologically observed in myocardial tissue sections. The oral pretreatment of β‐glucan prevented almost all the parameters of isoproterenol induced myocardial injury in rats. The above finding was confirmed by the histopathological analysis. These findings provided an evidence that β‐glucan could protect rat myocardium against ISO‐induced myocardial injury that was attributed to its antioxidant and anti‐apoptotic properties.

This article is protected by copyright. All rights reserved



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Meta-analyzability concerns in meta-analyses.

Publication date: Available online 25 January 2019

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Chih-Yang Hsu, Yen-Nung Lin

Abstract

Many studies to date have conducted a meta-analysis on a mix of effectiveness and superiority studies. This methodological flaw will lead to difficulties in interpreting the results. We addressed this issue in this article, illustrated our point with a simulated experiment, and re-analyzed a recent meta-analysis study based on the effectiveness-superiority dichotomy to provide a real-world correlate of our point of view.

The number of meta-analyses has increased astonishingly over the past few decades. (Figure 1) In 2016 alone, approximately 13 thousand new meta-analysis studies were indexed in PubMed, more than 200 of which are rehabilitation-related. The sophistication and availability of statistical software may have partially contributed to the prosperity. Here we would like to address an important issue which has usually been neglected—the meta-analyzability.

Meta-analyzability refers to the rationale to pool a bundle of trials with heterogeneity in a meta-analysis. The heterogeneity can exist in the participants, interventions, comparisons, or outcomes (PICO). Among them, the heterogeneity in comparison seems to have received less, and perhaps inadequate attention. The majority of trials exploring the beneficial effects of an experimental intervention (EI) can be classified into two kinds of study: effectiveness studies or superiority studies. The former compare the outcomes between the group receiving an EI and the group not receiving an EI, while the latter compare the outcomes between the group receiving an EI and the group receiving the standard or competing intervention (CI). The comparison formulas can be expressed as below:



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Diagnosis and Management in Pitt‐Hopkins Syndrome: First International Consensus Statement

Clinical Genetics Diagnosis and Management in Pitt‐Hopkins Syndrome: First International Consensus Statement

Pitt‐Hopkins syndrome (PTHS) is a neurodevelopmental disorder characterized by intellectual disability, specific facial features, and marked autonomic nervous system dysfunction, especially with disturbances of regulating respiration and intestinal mobility. It is caused by variants in the transcription factor TCF4. Heterogeneity in the clinical and molecular diagnostic criteria and care practices have prompted a group of international experts to establish guidelines for diagnostics and care. For issues, for which there was limited information available in international literature, we collaborated with national support groups and the participants of a syndrome specific international conference to obtain further information. Here, we discuss the resultant consensus, including the clinical definition of PTHS and a molecular diagnostic pathway. Recommendations for managing particular health problems such as dysregulated respiration are provided. We emphasize the need for integration of care for physical and behavioral issues. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimization of diagnostics and care.

This article is protected by copyright. All rights reserved.



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Putting Implementation Science into Practice: Lessons from the Creation of the National Maternal and Child Health Workforce Development Center

Abstract

Purpose This article describes how implementation science informed the design of a national training and technical assistance (TA) center, and how implementation best practices have been used to improve the quality of training and technical assistance services offered to states/jurisdictions. Description An existing tool, based on the Implementation Drivers Framework (in: Fixsen et al., Implementation research: a synthesis of the literature, University of South Florida, The National Implementation Research Network, Tampa, 2005), was adapted to assess efforts of the National MCH Workforce Development Center (the Center) against known implementation best practices. Staff identified specific examples of effective practice and gaps for inclusion in this article. Assessment Using implementation science to establish, assess and improve Center practice was both feasible and practical, requiring intentionality, dedicated time, and staff committed to deepening their understanding of implementation science. The Implementation Drivers framework proved useful for creating a shared approach to analysis and identification of opportunities for improvement of Center practice. Conclusion Policymakers and funding agencies should consider how training and technical assistance programs demonstrate knowledge and use of implementation science best practices among other evidence based practices in their work. Increasing attention to the use of implementation science can contribute to a higher quality of service among technical assistance centers, with the long term goal of improving outcomes for training and assistance recipients and the communities they serve. Establishing the link between customer satisfaction and quality of technical assistance, on the one hand, and long term outcomes, on the other, remains a challenge and an area of focus and learning for the Center.



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