Δευτέρα, 19 Νοεμβρίου 2018

The Role of Youth Trainee–Trainer Alliance and Involvement in School-Based Prevention: A Moderated-Mediation Model of Student Gatekeeper Suicide Prevention Training

Abstract

This study examined the roles that youth involvement and youth trainee–trainer alliance play in school mental health prevention within the context of youth suicide gatekeeper training. Measures included youth involvement in programming, trainee–trainer alliance, and intentions to refer at-risk youth at pre- and post-training. A moderated-mediation design was used to examine associations among these factors. Results show alliance mediating pre- and post-training referral intentions, and involvement moderating the relationship between alliance and post-training intentions. On average, trainee intentions improved from pre- to post-training, but trainees reporting high alliance endorsed higher post-training referral intentions regardless of involvement level. Low alliance resulted in lower than average post-training referral intentions, even with active involvement in programming, and those with both low alliance and involvement showed the lowest post-training referral intentions. Given these findings, fostering the youth trainee–trainer relationship may be an avenue to optimize prevention program effectiveness.



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An Additional 30-s Observation of the Right-Sided Colon with Narrow Band Imaging Decreases Missed Polyps: A Pilot Study

Abstract

Introduction

Previous narrow-band imaging (NBI) was dark and reported not to be useful for polyp detection. In this study, we analyzed the efficacy of an additional 30-s observation of the right-sided colon with the recent bright high-resolution NBI.

Methods

We enrolled patients undergoing colonoscopy from February 2015 to May 2017 in two institutions. All procedures were performed with the latest system (EVIS LUCERA ELITE, Olympus). The cecum and ascending colon were first observed with white light imaging (WLI) in both the NBI and WLI group. Then, the colonoscope was re-inserted, and the cecum and ascending colon were observed for an additional 30 s. In this second observation, NBI was performed for the first 130 patients in the NBI group and WLI for the next 130 in the WLI group. The number of adenoma and sessile serrated polyps (ASPs) in the second observation were examined in both groups. According to our initial pilot study, the sample size was estimated at 126.

Results

In the first observation, the number of ASPs was 72 in the NBI group and 72 in the WLI group (p = 1.0). In the second observation, the number of ASPs was 23 in the NBI group and 10 in the WLI group (p = 0.02). The polyp and adenoma detection rates in the second observation were 16.2% and 12.3% in the NBI group and 7.7% (p = 0.03) and 6.2% (p = 0.09) in the WLI group.

Conclusions

The additional 30-s observation with recent NBI decreased missed polyps in the right-sided colon.



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Incidence and Prognosis of Subsequent Cholangiocarcinoma in Patients with Hepatic Resection for Bile Duct Stones

Abstract

Background and Aim

Cholangiocarcinoma (CCA) often develops after the hepatic resection for hepatolithiasis as well as indwelling it. We studied the incidence and prognosis of subsequent CCA in patients with hepatolithiasis in South Korea.

Methods

We identified individuals with diagnosed CCA at the time of or after surgery, during 2002–2016, from the Korean National Health Insurance. The incidences and survival rates of subsequent CCA were analyzed and compared with concomitant CCA. The standardized incidence ratios (SIRs) of CCA in this cohort were evaluated in the standard Korean population. All data were stratified by the presence of intrahepatic or extrahepatic CCA, age and sex.

Results

Of the 7852 patients with hepatectomy for BDS, 433 (5.84%) had concomitant CCA. Over the 12-year follow-up, 107 of 7419 (1.98%) patients were diagnosed with subsequent CCA. Patients with hepatic resection for BDS revealed higher SIRs for subsequent CCA (12.89, 95% CI 10.96–15.15) in cases of both intrahepatic CCA (13.40, 10.55–17.02) and extrahepatic CCA (12.42, 9.98–15.46). The median survival time for subsequent CCA was 0.87 years, while that for concomitant CCA was 2.79 years. Having subsequent CCA (HR 2.71, 95% CI 2.17–3.40) and being male (HR 1.28, 1.05–1.57) were related to a shorter survival time. The CCA site and age at CCA diagnosis were not related to prognoses.

Conclusions

Subsequent CCA developed in 2% of the patients with hepatic resection for benign BDS until 10 years and was associated with poorer prognoses than concomitant CCA. Future studies focused on the long-term surveillance for CCA in such patients are needed.



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Evaluation of Biliary Bacterial Resistance in Patients with Frequent Biliary Instrumentation, One Size Does Not Fit All

Abstract

Background

Bacteremia due to cholangitis can occur as a complication of biliary instrumentation. Biliary sepsis can result from frequent endoscopic retrograde cholangiopancreatography (ERCP).

Methods

We hypothesized that routine use of antibiotics in patients who require frequent ERCPs leads to cholangitis resistant to empiric antibiotics used to treat biliary sepsis. We retrospectively reviewed patients with frequent biliary instrumentation and blood stream infection due to cholangitis. Conventional empiric antibiotics were defined as broad-spectrum antibacterial agents predominantly used for community-acquired infections and surgical prophylaxis. Broad-spectrum antibacterial agents used for hospital-onset/multidrug-resistant infections were defined as broad-spectrum MDR antibiotics.

Results

Seventy-eight patients had bacteremia secondary to cholangitis from biliary obstruction. Over 50% of bacteria were not sensitive to conventional empiric antibiotics for biliary sepsis. Thirty-seven patients did not receive post-procedural antibiotics and forty-one patients did. Of the ones who did, 58% later had a bloodstream infection with bacteria resistant to the antibiotic used for prophylaxis, and 26 patients (63%) required a broad-spectrum MDR antibiotic for treatment. The number of ERCPs was not associated with resistance to prophylactic antibiotics (p 0.7103) or needing broad-spectrum MDR antibiotics for treatment of cholangitis-associated bacteremia (p 0.1868). Routine use of antibiotic prophylaxis after ERCP was associated with trend toward need for broad-spectrum MDR antibiotics for cholangitis-associated bacteremia, Chi-square 3.7, 0 0.0540.

Conclusion

Bacterial resistance to conventional empiric antibiotics is an emerging problem. Blood cultures are needed to guide therapy.



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Retinoic Acid Receptor α Knockdown Suppresses the Tumorigenicity of Esophageal Carcinoma via Wnt/β-catenin Pathway

Abstract

Background

Aberrant expression of retinoic acid receptor α (RARα) was correlated with diverse carcinomas such as acute promyelocytic leukemia and colorectal carcinoma. Nevertheless, the function and mechanism of RARα in esophageal carcinoma (EC) remain unclear.

Aim

To investigate the expression of RARα in EC and its effect in the tumorigenesis of EC.

Methods and Results

In immunohistochemistry study, RARα was overexpressed in human EC tissues, and its overexpression was closely related to the pathological differentiation, lymph node metastasis, and clinical stages in EC patients. Functionally, RARα knockdown suppressed the proliferation and metastasis of EC cells through downregulating the expression of PCNA, Ki67, MMP7, and MMP9, as well as enhanced drug susceptibility of EC cells to 5-fluorouracil and cisplatin. Mechanistically, RARα knockdown inhibited the activity of Wnt/β-catenin pathway through reducing the phosphorylation level of GSK3β at Ser-9 and inducing phosphorylation level at Tyr-216, which resulted in downregulation of its downstream targets such as MMP7, MMP9, and P-gP.

Conclusions

Our results demonstrated that RARα knockdown suppressed the tumorigenicity of EC via Wnt/β-catenin pathway. RARα might be a potential molecular target for EC clinical therapy.



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Excess Alcohol Consumption: A Potential Mechanism Behind the Association Between Small Intestinal Bacterial Overgrowth and Coronary Artery Disease



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Winged Partially Covered Self-Expandable Metal Stent to Prevent Distal Migration in Malignant Gastric Outlet Obstruction

Abstract

Background

Through-the-scope implantation of self-expandable metal stents can be used for the palliation of malignant gastric outlet obstruction. Although covered stents were developed to prevent tumor ingrowth, often seen with uncovered stents, migration is still a major problem. Especially, surgical treatment is required for some patients if distal migration occurs.

Aims

To evaluate the usefulness of the newly designed winged stent that was developed to prevent distal stent migration.

Methods

This was a single-center, single-arm, retrospective study. A total of 63 inoperable cancer patients with symptomatic gastric outlet obstruction were reviewed to evaluate the safety and efficacy of a newly designed partially covered self-expandable metal stent with star-shaped wing flaps at the proximal end to reduce distal stent migration.

Results

Technical and clinical successes were achieved in 100% and 87.3% of patients, respectively. The gastric outlet obstruction scoring system score significantly improved after stent placement (from median 1 to 2, P < 0.001). The median duration of stent patency was 147 days (interquartile range 76–201), and median duration of overall survival was 176 days (interquartile range 79–325). Stent migration was observed in seven patients (11.1%), and restenosis was developed in 12 patients (19.0%). All cases of migration were proximal, and no distal migration was observed. Endoscopic removal of migrated stents was performed successfully in all cases.

Conclusions

The newly designed winged stent showed feasible efficacy and safety for malignant gastric outlet obstruction. Furthermore, it effectively prevented distal stent migration.



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BH3 Mimetic ABT-199 Enhances the Sensitivity of Gemcitabine in Pancreatic Cancer in vitro and in vivo

Abstract

Background and Aims

Pancreatic cancer is an aggressive malignancy with poor prognosis. Gemcitabine is the standard chemotherapeutic drug used to treat the disease; however, it has a low response rate. Therefore, there is an urgent need to develop new and safe therapies to enhance sensitivity to gemcitabine in treating pancreatic cancer.

Methods

The synergistic effect of gemcitabine combined with specific B cell CLL/lymphoma 2 (Bcl-2) inhibitor ABT-199 against pancreatic cancer was tested using cell viability, cell cycle, and apoptosis assays in vitro and in an MIA Paca-2 xenograft model in vivo. Its underlying mechanism was explored using western blotting analysis of Bcl-2 family proteins.

Results

ABT-199 not only enhanced the effect of gemcitabine on cell growth inhibition but also promoted gemcitabine-induced apoptosis in pancreatic cancer cell lines. Gemcitabine decreased the expression of anti-apoptotic protein Mcl-1 but increased the expression of anti-apoptotic protein Bcl-2. ABT-199 downregulated the gemcitabine-induced production of Bcl-2 and increased the expression of pro-apoptotic protein Bcl-2 interacting protein (BIM). Mouse xenograft experiments also confirmed the synergistic effect of gemcitabine and ABT-199 on tumor growth inhibition and the induction of tumor cell apoptosis.

Conclusion

Our results indicated that ABT-199 improved the anti-tumor effect of gemcitabine on pancreatic cancer by downregulating gemcitabine-induced overexpression of Bcl-2. ABT-199 has already been investigated in phase 3 clinical trials for chronic lymphocytic leukemia; therefore, it may serve as a potential drug to improve the sensitivity of pancreatic cancer to gemcitabine.



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Lack of Patient Compliance in Real-World Practice Negatively Affects Sustained Viral Response Rates to Direct Acting Agent Therapy for Hepatitis C

Abstract

Objective

To assess the true efficacy of direct acting antiviral (DAA) therapy in real-world clinical practice, taking into account those patients that do not complete therapy or the necessary follow-up to establish sustained viral response (SVR).

Methods

Retrospective data collection of 261 genotype 1 HCV-infected patients, treatment naïve or treatment experienced, treated with ledipasvir/sofosbuvir combination therapy at an academic medical center. All patients received individualized teaching and counseling prior to starting therapy stressing importance of compliance with laboratory monitoring and treatment completion. Intention to treat SVR rates (ITT-SVR) and per-protocol SVR rates (PP-SVR) were calculated. Chi-squared test was used to compare the number of subjects lost to follow-up in the treatment-naïve vs. treatment-experienced groups. Characteristics of noncompliant patients were compared to compliant patients.

Results

ITT-SVR rates for the entire cohort were 74%, significantly lower than the 95% PP-SVR rate for the compliant patients (p < 0.001). ITT-SVR was lower in treatment-naïve patients compared to treatment-experienced patients (68% vs. 86%). Among the entire cohort, 22% of patients either discontinued therapy prematurely (7%) or did not return for SVR assessment (15%). Failure to complete therapy or return for SVR assessment was statistically more common among treatment-naïve patients compared to treatment-experienced patients (28% vs. 11%, p = 0.0016).

Conclusions

There is a significant rate of noncompliance among patients treated with DAA in real-world clinical practice despite pre-treatment education efforts. The ITT-SVR rates observed in clinical practice were significantly lower than those reported by clinical trials, and this difference was most pronounced among treatment-naïve patients.



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Colonic Hypermotility in a Rat Model of Irritable Bowel Syndrome Is Associated with Upregulation of TMEM16A in Myenteric Plexus

Abstract

Background

Irritable bowel syndrome (IBS) is a common disease with intestinal dysmotility, whose mechanism remains elusive. TMEM16A is a calcium-activated chloride channel (CaCC) involved in intestinal slow-wave generation.

Aims

To investigate whether TMEM16A is involved in colonic dysmotility in IBS.

Methods

A rat model of IBS was established by chronic water avoidance stress (WAS). Colonic pathological alterations were evaluated histologically, and intestinal motility was assessed by intestinal transit time (ITT) and fecal water content (FWC). Visceral sensitivity was determined by visceromotor response (VMR) to colorectal distension (CRD). TMEM16A expression was evaluated by RT-PCR, Western blot, and immunofluorescence. Colonic muscle strip contractility was measured by isometric transducers, and the effect of niflumic acid (NFA), a CaCC antagonist, on colonic motility was examined.

Results

After 10 days of WAS exposure, ITT was decreased and FWC was elevated. Furthermore, VMR magnitude of WAS rats in response to CRD was significantly enhanced. Protein and mRNA levels of TMEM16A in colon were considerably increased after WAS. The percentage of TMEM16A-positive neurons in myenteric plexus (MP) of WAS rats was significantly higher than controls. Pharmacological blockade of TMEM16A activity by NFA considerably enhanced ITT, with concentration-dependent declines in FWC and VMR magnitude in NFA-treated rats. Further, spontaneous contraction of colonic strips of NFA-treated rats was significantly ameliorated in a concentration-dependent manner in vitro.

Conclusions

Upregulation of TMEM16A in MP neurons may play an important role in chronic stress-induced colonic hypermotility, making CaCC-blocking drugs a putatively effective treatment method for colonic hypermotility in IBS.



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Microbial Biomarkers in Patients with Nonresponsive Celiac Disease

Abstract

Background and Aims

In nonresponsive celiac disease (NRCD), the symptoms and duodenal damage persist despite a gluten-free diet. Celiac disease patients with persistent symptoms are found to have a dysbiotic microbiota. We thus hypothesized that increased seroreactivity to the serum gluten-sensitive microbial antibodies Saccharomyces cerevisiae (ASCA), Pseudomonas fluorescens-associated sequence (I2), and Bacteroides caccae TonB-linked outer membrane protein (OmpW) is associated with NRCD.

Methods

ASCA, I2 and OmpW were measured in 20 seronegative CD patients with persistent villous damage despite strict dietary treatment (NRCD group). Fifty-eight responsive patients served as CD controls (55 on gluten-free treatment) and 80 blood donors as non-CD controls.

Results

At least one microbial marker was positive in 80% of NRCD patients, in 97% of untreated CD and 87% of treated CD patients, and in 44% of controls. NRCD patients had the highest frequency of ASCA positivity (65% vs 52, 20, and 0%, respectively) and also significantly higher ASCA IgA (median 14.5 U/ml) and IgG (32.5 U/ml) titers than treated CD patients (7.0 U/ml, 13.0 U/ml) and non-CD controls (4.5 U/ml, 5.8 U/ml). The frequencies of I2 and OmpW were lower in NRCD than in untreated CD (65% and 45% vs 86% and 59%, respectively), and I2 titers were higher in NRCD (median absorbance 0.76) and untreated (1.0) and treated (0.83) CD than controls (0.32). OmpW was elevated in untreated (1.1) and treated (0.94) CD patients compared with controls (0.79).

Conclusions

Seropositivity and high titers of ASCA are associated with NRCD and might serve as an additional follow-up tool in CD.



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Epidermal Growth Factor Receptor Mutation Detection in Cerebrospinal Fluid of Lung Adenocarcinoma Patients with Leptomeningeal Metastasis

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


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Bridge-to-surgery versus emergency surgery in the management of left-sided acute malignant colorectal obstruction — efficacy, safety and long-term outcomes

Compare efficacy, safety and long-term outcomes of bridge-to-surgery and emergency surgery in acute malignant colorectal obstruction.

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Presence of hepatitis B virus markers in umbilical cord blood: exposure to or infection with the virus?

We aimed to clarify whether presence of hepatitis B virus (HBV) markers in cord blood indicates exposure to or infection with HBV.

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Blood Magazines

Are you wondering what the title of this editorial means? If yes, then good. I've got your attention. For this, my first editorial as the Editor in Chief of The Spine Journal (I still can't believe it!), my goal is to not be boring. There are, in fact, many not boring changes, modifications, and updates to tell you about. I'll leave those for another issue, after the initial shock of seeing my name at the top of the masthead page.

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Prediction of Subgenome Additive and Interaction Effects in Allohexaploid Wheat

Whole genome duplications have played an important role in the evolution of angiosperms. These events often occur through hybridization between closely related species, resulting in an allopolyploid with multiple subgenomes. With the availability of affordable genotyping and a reference genome to locate markers, breeders of allopolyploids now have the opportunity to manipulate subgenomes independently. This also presents a unique opportunity to investigate epistatic interactions between homeologous orthologs across subgenomes. We present a statistical framework for partitioning genetic variance to the subgenomes of an allopolyploid, predicting breeding values for each subgenome, and determining the importance of intergenomic epistasis. We demonstrate using an allohexaploid wheat breeding population evaluated in Ithaca, NY and an important wheat dataset from CIMMYT previously shown to demonstrate non-additive genetic variance. Subgenome covariance matrices were constructed and used to calculate subgenome interaction covariance matrices for variance component estimation and genomic prediction. We propose a method to extract population structure from all subgenomes at once before covariances are calculated to reduce collinearity between subgenome estimates. Variance parameter estimation was shown to be reliable for additive subgenome effects, but was less reliable for subgenome interaction components. Predictive ability was equivalent to current genomic prediction methods. Including only inter-genomic interactions resulted in the same increase in accuracy as modeling all pairwise marker interactions. Thus, we provide a new tool for breeders of allopolyploid crops to characterize the genetic architecture of existing populations, determine breeding goals, and develop new strategies for selection of additive effects and fixation of inter-genomic epistasis.



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A Low Resolution Epistasis Mapping Approach To Identify Chromosome Arm Interactions in Allohexaploid Wheat

Epistasis is an important contributor to genetic variance. In inbred populations, pairwise epistasis is present as additive by additive interactions. Testing for epistasis presents a multiple testing problem as the pairwise search space for modest numbers of markers is large. Single markers do not necessarily track functional units of interacting chromatin as well as haplotype based methods do. To harness the power of multiple markers while minimizing the number of tests conducted, we present a low resolution test for epistatic interactions across whole chromosome arms. Epistasis covariance matrices were constructed from the additive covariances of individual chromosome arms. These covariances were subsequently used to estimate an epistatic variance parameter while correcting for background additive and epistatic effects. We find significant epistasis for 2% of the interactions tested for four agronomic traits in a winter wheat breeding population. Interactions across homeologous chromosome arms were identified, but were less abundant than other chromosome arm pair interactions. The homeologous chromosome arm pair 4BL/4DL showed a strong negative relationship between additive and interaction effects that may be indicative of functional redundancy. Several chromosome arms appeared to act as hubs in an interaction network, suggesting that they may contain important regulatory factors. The differential patterns of epistasis across different traits demonstrates that detection of epistatic interactions is robust when correcting for background additive and epistatic effects in the population. The low resolution epistasis mapping method presented here identifies important epistatic interactions with a limited number of statistical tests at the cost of low precision.



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Trends in robot-assisted and virtual reality-assisted neuromuscular therapy: a systematic review of health-related multiplayer games

Multiplayer games have emerged as a promising approach to increase the motivation of patients involved in rehabilitation therapy. In this systematic review, we evaluated recent publications in health-related m...

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The Future of Maternal and Child Health

Abstract

Introduction

The purpose of this commentary is to start a national conversation about the future of maternal and child health (MCH). In the coming decades, we will have unprecedented opportunities to improve MCH, but will also face unprecedented threats.

Methods

This paper examines emerging opportunities and threats to MCH, and discusses strategies for leading the future of MCH.

Results

Scientific advancements will continue to drive improvements in MCH, but to unleash its full potential for improving population health future MCH research must become more transdisciplinary, translational, and precise. Technological innovations could dramatically transform our work in MCH while big data could enhance predictive analytics and precision health; our challenge will be to assure equitable access. The greatest gains in MCH will continue to come from improving social conditions, which will require advancing MCH in all policies. Climate change, infectious outbreaks and antimicrobial resistance pose increasing threats to MCH, which can be averted by reducing global warming, implementing global early warning systems, and instituting responsible antimicrobial stewardship. The growing burden of chronic diseases in children and adults need to be addressed from an ecological and life course perspective. The water crisis in Flint shined a spotlight on the growing health threats from America's decaying infrastructure.

Discussion

We can lead the future of MCH by starting a national conversation, improving MCH research, and preparing future MCH workforce, but the future of MCH will depend on our effectiveness in bringing about social and political change in the coming decades.



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A case of gossypiboma diagnosed with transanal double-balloon enteroscopy

Abstract

Gossypiboma is an iatrogenic granuloma caused by retained surgical gauze. A 48-year-old woman with a history of cesarean section was incidentally found to have a pelvic mass on preoperative computed tomography examination for pectus excavatum. Abdominal enhanced computed tomography showed a 40-mm mass containing air in the pelvis. The mass was suspected to be continuous with the ileum. Transanal double-balloon enteroscopy showed a small fistula that was likely caused by penetration of the ileum dozens of centimeters from the ileocecal valve. A yellow–brown, movable, and fibrous body was found in the fistula. A part of the fibrous body was extracted with forceps. Pathological examination revealed that it was gauze. This is the first reported case of an asymptomatic gossypiboma penetrating the ileum that was diagnosed with double-balloon enteroscopy. Our results suggest that double-balloon enteroscopy is useful for early diagnosis of pelvic mass penetrating intestine, including gossypiboma.



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Electrohydraulic Lithotripsy for Pancreatic Duct Stones Under Digital Single-Operator Pancreatoscopy (with Video)

Abstract

Background

Recently, a digital single-operator cholangiopancreatoscope (DSOC) has become available. This system allows the performance of electrohydraulic lithotripsy (EHL) even within the main pancreatic duct (MPD). However, there are only few reports of EHL for MPD stones using SPY-DS.

Aims

The aim of this study was to evaluate the technical feasibility and efficacy of EHL for MPD stones under DSOC guidance.

Methods

Between October 2016 and August 2017, patients with MPD stones were retrospectively enrolled in this study. The presence of MPD stones was diagnosed by endoscopic ultrasound and MRCP. The patients' baseline characteristics and those of the stones, including their size, number, and site in the MPD, number of EHL procedures, and adverse events, were reviewed.

Results

A total of 21 patients were retrospectively enrolled. The etiologies of chronic pancreatitis were idiopathic (n = 4) and alcohol induced (n = 17). The pancreatic stone was variously located in the head (n = 6), body (n = 11), tail (n = 1), head and body (n = 2), and body and tail (n = 1) of the pancreas. Median pancreatic stone size was 12 mm, and the mean number of ERCP sessions was 1.29 (range 1–3). EHL was successfully performed in 15 patients (85.7%, 18/21), and the rate of complete stone clearance was 88.2% (18/21). Severe adverse events were not seen in any of the patients, although one patient developed mild acute pancreatitis.

Conclusions

In conclusion, although additional case reports and prospective studies are needed, EHL under DSOC may be an option to treat MPD stones.



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TaF: a web platform for taxonomic profile-based fungal gene prediction

Abstract

Introduction

The accurate prediction and annotation of gene structures from the genome sequence of an organism enable genome-wide functional analyses to obtain insight into the biological properties of an organism.

Objectives

We recently developed a highly accurate filamentous fungal gene prediction pipeline and web platform called TaF. TaF is a homology-based gene predictor employing large-scale taxonomic profiling to search for close relatives in genome queries.

Methods

TaF pipeline consists of four processing steps; (1) taxonomic profiling to search for close relatives to query, (2) generation of hints for determining exon–intron boundaries from orthologous protein sequence data of the profiled species, (3) gene prediction by combination of ab inito and evidence-based prediction methods, and (4) homology search for gene models.

Results

TaF generates extrinsic evidence that suggests possible exon–intron boundaries based on orthologous protein sequence data, thus reducing false-positive predictions of gene structure based on distantly related orthologs data. In particular, the gene prediction method using taxonomic profiling shows very high accuracy, including high sensitivity and specificity for gene models, suggesting a new approach for homology-based gene prediction from newly sequenced or uncharacterized fungal genomes, with the potential to improve the quality of gene prediction.

Conclusion

TaF will be a useful tool for fungal genome-wide analyses, including the identification of targeted genes associated with a trait, transcriptome profiling, comparative genomics, and evolutionary analysis.



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Prediction of Y haplogroup by polymerase chain reaction-reverse blot hybridization assay

Abstract

Background

The analysis of Y-SNPs from crime scene samples is helpful for investigators in narrowing down suspects by predicting biogeographical ancestry.

Objective

In this study, a PCR-reverse blot hybridization assay (REBA) for predicting Y-chromosome haplogroups was employed to determine the major haplogroups worldwide, including AB, DE, C, C3, F, K, NO, O, O2, and O3 and evaluated.

Methods

The REBA detects nine biallelic Y chromosome markers (M9, M89, M122, M145, M175, M214, M217, P31, and RPS4Y711) simultaneously using multiple probes.

Results

The REBA for Y-single nucleotide polymorphisms (SNP) genotyping was performed using 40 DNA samples from Asians—14 Koreans, 10 Indonesians, six Chineses, six Thais, and four Mongolians. 40 Asian samples were identified as haplogroup O2 (40%), O3 (32.5%), C3 (17.5%), O (7.5%) and K (2.5%). These cases were confirmed by DNA sequence analysis (κ = 1.00; P < 0.001).

Conclusion

PCR-REBA is a rapid and reliable method that complements other SNP detection methods. Therefore, implementing REBA for Y-SNP testing may be a useful tool in predicting Y-chromosome haplogroups.



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Genome-wide identification of the HKT genes in five Rosaceae species and expression analysis of HKT genes in response to salt-stress in Fragaria vesca

Abstract

Introduction

The high-affinity potassium transporter (HKT) gene family is implicated in the regulation of response to salt stress in different plants. Yet, knowledge remains very limited for them in the Rosaceae species. The whole genome sequences of the five Rosaceae species, including Fragaria vesca (woodland strawberry), Malus domestica (apple), Pyrus communis (pear), Prunus mume (mei) and Prunus persica (peach), give the opportunity to uncover the evolutionary pattern of the HKT genes among Rosaceae genomes.

Objectives

The primary objective of this study was to identify the HKT genes in five Rosaceae species and understand the potential biological functions of the HKT genes in response to salt stress in Fragaria vesca.

Methods

In this study, the HKT genes in five Rosaceae species were identified by bioinformatics. The phylogenetic tree was constructed and Ka and Ks values were calculated by MEGA 5.0. Genetic mapping of these genes were processed by MapInspect software. In addition, the physico-chemical properties, the cis-acting elements, the intron/exon structures, and the conserved domain motifs of these genes were analyzed and predicted by the websites of ProtParam, Pfam, PlantCARE, GSDS, MEME, and Motif Scan.

Results

In the present study, a total of 12 HKT genes were identified from five Rosaceae species. In the phylogenetic tree, orthologous genes were clustering together rather than paralogous genes and PcHKTs underwent two species-specific duplications before the divergence of pear and apple.. Furthermore, various expression levels of FvHKT genes revealed that woodland strawberry HKT genes are associated in responding to the salt stress. The activities of ROS-scavenging enzymes, superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) were also measured in different treatments of salt-stressed woodland strawberry leaves, which suggested that the three enzymes may also take part in response to salt stress.

Conclusion

The Ka/Ks ratio demonstrated that purifying selection played a major role in the evolutionary processes of HKT genes among the Rosaceae species, and FvHKT genes are involved in response to salt stress.



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Characterization of chloroplast genomes of Alnus rubra and Betula cordifolia , and their use in phylogenetic analyses in Betulaceae

Abstract

Objective

Betulaceae is a relatively small birch family that comprises about 160 deciduous trees and shrubs. Chloroplast (cp) genome sequencing of Alnus rubra and Betula cordifolia was carried out to elucidate their molecular features and phylogenetic relationship among species in Betulaceae family.

Methods

Chloroplast genome sequencing was carried out using next generation sequencing method. Molecular and genomic features of the two cp genomes were characterized with other cp genomes in Betulaceae. Also, molecular phylogenetic analysis was performed using the whole cp genome sequences.

Results

The average cp genome length was 160,136 bp among the Betulaceae species. Base compositions of the cp genomes were skewed toward a high AT ratio, with an average of 63.4%. We identified 117 different genes 83 with protein coding, 4 with ribosomal RNA, and 30 with tRNA. Eighteen genes contained introns which were conserved among the cp genomes of all Betulaceae. We mined 82 SSRs from the cp genomes of A. rubra, A. cordifolia, and A. nana. The SSRs were variable in motif repeat numbers and presence/absence among the cp genomes.

Conclusion

Chloroplast genome-wide sequence comparison from 11 Betulaceae species and one cp genome of evergreen oak revealed that the patterns of sequence variations were congruent with two subfamily classification Betuloideae (Alnus and Betula) and Corylaceae (Corylus, Ostrya, and Carpinus). Subsequent phylogenetic analysis also supports the sub-classifications of these species.



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The structural and functional roles of CTCF in the regulation of cell type-specific and human disease-associated super-enhancers

Abstract

Background

Super-enhancers play critical roles in cell-type specific gene controls and human disease progression. CCCTC-binding factor (CTCF), a transcriptional repressor that insulates the expression of neighboring genes and is involved in chromatin interactions, is frequently present in the boundary regions of or within super-enhancers. However, the structural and functional roles of CTCF in regulating super-enhancers remain elusive.

Objective

To provide a comprehensive review describing the distinct chromatin features and functional roles of CTCF within super-enhancers.

Methods

This review compares the various tools used to study the three-dimensional (3D) chromatin architecture of super-enhancers; summarizes the chromatin features of CTCF within cell-type specific super-enhancers and their in vivo biological activities, as determined by CRISPR/Cas9 genome editing; and describes the structural and functional activities of CTCF within human disease-associated super-enhancers.

Conclusion

This review provides fundamental insights into the regulatory mechanisms of super-enhancers and facilitates studies of tissue-specific developmental processes and human disease progression.



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Identifying natural genotypes of grain number per panicle in rice ( Oryza sativa L.) by association mapping

Abstract

Introduction

As one of the main yield components, grain number per panicle (GNP) played critical role in the rice yield improvement. The identification of natural advantageous variations under different situations will promote the sustainable genetic improvement in rice yield.

Objectives

This study was designed to identify natural genotypes in a rice mini-core collection, to examine the genotypic effects across the indica and japonica genetic background in different environments, and excavating the superior genotypes that had drove the modern genetic improvement.

Methods

The association mapping of GNP was carried out using a mini-core collection including 154 indica and 119 japonica accessions in seven different environments. Genotypic effects of each genotype for each QTL were calculated and genotype frequency distortion between the commercial rice cultivars and landraces was screened by χ2-test.

Results

In total, 74 QTLs containing stable and sensitive QTLs in various environments were detected. Within them, 20 positive and 24 negative genotypes in indica, and 24 positive and 16 negative genotypes in japonica were identified. When checking the accumulation of positive genotypes identified in indica across cultivars in each of the two subspecies, it indicated that increased number of positive genotypes identified in indica results in the substantially increased GNP in both indica and japonica across all of the environments, while this trend was not obvious for the positive genotypes identified in japonica especially in short day environments. Moreover, the positive and negative genotype frequency distortion between the landraces and commercial rice cultivars indicated that both positive selection of positive genotypes and negative selection of negative genotypes had driven the genetic improvement on GNP.

Conclusion

Our findings suggested that the accumulation of positive genotypes and purifying negative genotypes played equivalently important roles in the improvement of rice yield, but the efficient use for some QTLs or genotypes depends on the comprehensive evaluation of their effect under diverse genetic backgrounds and environments.



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Perioperative management of tracheocutaneous fistula closure in children: A review of 96 cases

Summary

Background

A tracheocutaneous fistula is a known complication following tracheostomy decannulation. Although surgical techniques for its repair are well described, there is no consensus about perioperative management and this procedure may generate significant airway and respiratory complications intraoperatively, and in the early postoperative period. We aimed to describe variations in perioperative management in tracheocutaneous fistula closure, estimate the incidence of early airway and respiratory complications, and identify any predisposing factors.

Methods

The otorhinolaryngology surgical database identified 118 tracheocutaneous fistula closures from August 1994 to September 2015. Ninety‐seven case notes were located generating 96 procedures for retrospective review. The data collected included demographics, comorbidities, anesthetic, and surgical technique, and complications up to 24 hours postoperatively.

Results

The median age at surgery was 5 years 10 months (range 1 year 8 months to 19 years 6 months). Preoperatively, 72% of patients had a "mini" sleep study (where the tracheocutaneous fistula is covered and saturations measured overnight). Ninety percent had an inhalational induction and 96% a tracheal intubation. Intraoperatively, laryngospasm occurred in 2% and there was difficulty ventilating in another 2%. A "leak test" to check fistula repair airtightness was recorded in 35%. Postoperatively 24% had one or more episodes of oxygen desaturation. Major complications occurred in five patients (incidence 5%, 95% CI 0.8‐9.7); four patients had pneumothoraxes with two needing postoperative mechanical ventilation and one patient developed life‐threatening subcutaneous emphysema.

Conclusion

Perioperative care for children undergoing tracheocutaneous fistula closure was not standardized. Advocated tests such as preoperative "mini" sleep studies and "leak test" intraoperatively were not consistently performed. Intraoperative anesthetic complications were uncommon; however, major postoperative respiratory complications were 5%.



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Sedation effects of intranasal dexmedetomidine combined with ketamine and risk factors for sedation failure in young children during transthoracic echocardiography

Summary

Background

Sedation is often required for young children during transthoracic echocardiography. Dexmedetomidine and ketamine are two sedatives that are commonly used in children for procedural sedation, but they have some disadvantages when they are used alone.

Aims

The aim of this retrospective study was to analyze the effects and safety of intranasal sedation with a combination of dexmedetomidine and ketamine during transthoracic echocardiography in young children and to analyze risk factors for sedation failure.

Methods

After IRB approval, we retrospectively evaluated data on patients who underwent echocardiography between May 2016 and August 2017 utilizing a combination of dexmedetomidine 2 μg/kg and ketamine 1 mg/kg. We collected information including heart rate, pulse oxygen saturation, sedation onset time, exam time, recovery time, and adverse reactions. Stepwise logistic regression analyses were performed to analyze the risk factors for sedation failure.

Results

Sedation was successful in 2212 patients (96%) and took effect in 15.7 (IQR: 10‐23) min, while sedation failed in 92 patients. Cyanotic heart disease, history of sedation failure, history of congenital heart disease surgery, and fever were independent risk factors for sedation failure. Most of the patients in this study had an American Society of Anesthesiologists (ASA) grade of II to III, but no severe adverse reactions were observed.

Conclusion

Intranasal sedation with a combination of dexmedetomidine and ketamine is effective and appears to have an acceptable safety profile for young children during transthoracic echocardiography.



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Increasing Stroke Knowledge and Decreasing Stroke Risk in a Latino Immigrant Population

Abstract

Stroke knowledge is poor and stroke risk is growing for the U.S. Latino immigrant population. We present results of an evaluation of a tailored, community-based intervention in Durham, North Carolina. The intervention included integration of stroke knowledge into classes and workshops at a community-based organization. Knowledge surveys were administered to participants immediately before and after stroke education, and at multiple points over the following year. For both low-risk participants receiving classroom-based education and individually care managed participants with risk factors, stroke knowledge improved dramatically and remained high among those who could be reached for follow-up. Evidence of behavior change and change in clinical status was weak. These findings from an observational study conducted in a real-world context complement the results of previously reported efficacy studies, indicating potential gains from health education for Latino immigrants, even from classroom-based education for low-risk individuals.



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The Role of Physician Recommendation in Colorectal Cancer Screening Receipt Among Immigrant Chinese Americans

Abstract

Chinese Americans have low colorectal cancer (CRC) screening rates. It is unclear whether physicians should offer all CRC screening modalities (fecal occult blood test [FOBT], sigmoidoscopy, colonoscopy) to Chinese Americans to increase screening. Seven hundred and twenty-five Chinese Americans were asked in a survey if their physician had ever recommended CRC screening and to self-report receipt and type of CRC screening. Participants whose physician had recommended all CRC screening modalities were significantly more likely to report ever having screening (adjusted odds ratio 4.29, 95% CI 1.26–14.68) and being up-to-date (4.06, 95% CI 2.13–7.74) than those who reported that their physician only recommended FOBT. Participants who received a recommendation of only one type of screening did not report a significant difference in ever having or being up-to-date for screening. A potential strategy to increase CRC screening among Chinese Americans is for clinicians to recommend all available CRC screening modalities to each patient.



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Socioeconomic Status and Glycemic Index Among Punjabis in Kuala Lumpur, Malaysia: Possible Association with Metabolic Syndrome

Abstract

There are only limited reports on Punjabi's health status in Malaysia. This cross-sectional study assessed the prevalence of metabolic syndrome (Mets) and its risk factors among 277 subjects recruited from the Malaysian Punjabi community. Overall prevalence of Mets was 43%, but 61% among females. Subjects classified with Mets had significantly (p < 0.05) higher body mass index, visceral fat and percentage of body fat. Daily carbohydrate and glycemic index (GI) were also higher among Mets subjects (p < 0.05). Logistics regression analysis showed that primary level of education (OR 5.57, CI 1.29–23.97, p = 0.021) was a factor associated with Mets, followed by middle household income (OR 2.30, CI 1.01–5.20, p = 0.046), GI (OR 1.03, CI 1.00–1.06, p = 0.026), and age (OR 1.03, CI 1.00–1.05, p = 0.023). Mets shows high prevalence among the studied Punjabi population, prompting the consideration of adequate preventive measures, primarily among lower socioeconomic groups.



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Migration Background Influences Consumption Patterns Based on Dietary Recommendations of Food Bank Users in Germany

Abstract

People with low income tend to eat less balanced than people with higher income. This seems to be particularly the case for people with migration background. This cross-sectional study examined the relation of consumption patterns of 597 food bank users with different migration background in Germany. Questionnaires were distributed assessing sociodemographic information and consumption patterns. Analyses were conducted using binary logistic regressions. Models were controlled for age, gender, type of household and education. The group of German food bank users consumed fewer fruits and vegetables and less fish compared to all other groups with migration background (former USSR, Balkan region, Middle East). A significant predictor for fruit and vegetable consumption was migration status. Participants from the former USSR consumed less often SSBs compared to the other groups. Dietary recommendations for low income populations should take into consideration other aspects besides income such as migration status.



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The Association Between the Intersection of Immigrant Status and Insurance with Adverse Birth Outcomes Among Mexican Women Residing in the San Joaquin Valley: A Mediation Analysis of Late Initiation or No Prenatal Care

Abstract

Latinos are the largest growing population and have the highest fertility rates in the US. In response, this study assessed if late initiation of or no prenatal care (PNC) mediated the relationship among adverse birth outcomes and interactions between immigrant and insurance status. This study used cross-sectional data (2002–2004) limited to 109,399 women of Mexican ethnicity who had singleton births in the San Joaquin Valley, California. We conducted hierarchical mediation analyses. US-born Mexican women who used private or public insurance for PNC were more likely to have infants born at low-birth weight and premature compared to Mexican first generation immigrant women. Nonetheless, initiation of late or no PNC positively mediated the relationship between infants born premature to Mexican first generation immigrant women who used public insurance (ab/se(ab) = 2.123, p = .034). Findings from this study support acculturation theory and the need for multilevel approaches to address PNC among women of Mexican ethnicity.



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Depressive and Anxiety Symptoms in Dutch Immigrant and Native Dialysis Patients

Abstract

Due to continuing migration there is more interest in the mental health status of immigrants. The aim of this study is to determine the prevalence of depressive/anxiety symptoms in immigrant and native dialysis patients, and to explore if patient characteristics can explain differences. The Beck depression inventory and the beck anxiety inventory were used. Differences between native and immigrant patients were explored using logistic regression models adjusted for patient characteristics. The prevalence of depressive symptoms was 35% for 245 native patients and 50% for 249 immigrant patients. The prevalence of anxiety symptoms was 35% for native patients and 50% for immigrant patients. In addition, the prevalence for co-morbid depressive and anxiety symptoms was 20% for native patients and 32% for immigrant patients. Crude ORs for depressive/anxiety symptoms for immigrant patients versus native patients were 1.8 (1.2–2.5) and 1.7 (1.2–2.5), respectively. After adjustment for patient characteristics ORs remained the same. Clinicians should be aware that immigrant dialysis patients are more prone to develop depressive and anxiety symptoms. Cultural factors might play a role and should therefore be assessed in future research.



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Access to and Use of Psychiatric Services by Migrants Resettled in Northern Italy

Abstract

The present study was conducted to describe access to and use of psychiatric services by migrants resettled in a large and well-defined catchment area. The study was conducted in a catchment area of 459,536 inhabitants in Verona, a city located in the Northeast of Italy. Using a psychiatric case register, all native and migrant individuals with a first ever psychiatric contact from 2000 to 2015 were identified. Service use data during the 12 months following first contact were collected. During the study period a total of 2610 migrants and 28,860 natives had at least one psychiatric contact. A progressive rise in the proportion of migrants seeking psychiatric care was observed, from 2.5% in 2000 to more than 14% in 2015. During the 12 months following first contact, the proportion of patients with a single consultation did not differ between resettled migrants and natives. However, migrants were more often marked users or heavy users of psychiatric services. Multivariate linear regression analyses showed that younger male individuals with psychotic disorders experienced higher psychiatric services use regardless their native or migrant condition. In a large catchment area with a well-developed community-based system of mental health care a progressive rise in the number of migrants seeking psychiatric care was observed. The pattern of service use during the 12 months after first contact was not related to nationality, suggesting the capacity of community psychiatric services to retain people in care. These findings call for the development of culturally and linguistically appropriate community psychiatric services.



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Prevalence and Types of Anemia in a Large Refugee Cohort in Western Europe in 2015

Abstract

Currently, vast numbers of migrants with largely unknown health statuses have been entering Europe. To improve care taking strategies, prevalence, severity and types of anemia in a large refugee cohort were assessed. Blood counts were performed in n = 787 inhabitants from six German refugee centers. Most included migrants were young, male adults. Anemia was present in 22.5% of subjects with an age-dependent prevalence increase (7.9% > 18 years vs. 30.8% > 50 years). More females than males were anemic (27.1% vs. 20.4%). The majority of affected migrants had mild anemia (86.2%) of either normocytic/normochromic (55.9%) or microcytic/hypochromic (20.9%) type. Observed anemia frequencies are in accordance with global anemia prevalence recently estimated by the WHO. However, the observed high rates of anemia particularly in female and older refugees emphasize the need for adapted care taking strategies in refugee medicine. Further evaluation of causes of anemia in the migrating population is needed.



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Prevalence and Risk Factors Associated with Self-Rated Morbidities Among South Asian Migrant Gas Station Workers in Kuwait

Abstract

Gas station workers (GSWs) are at elevated risk of morbidities associated with exposure to petrochemical substances. This cross-sectional study assessed the prevalence and examined demographics and occupation-related risk factors associated with self-rated ill-health among GSWs in Kuwait. Structured questionnaire was used to record self-rated ill-health from 460 selected GSWs of South-Asian origin. Prevalence of self-rated ill-health conditions was computed. Random-intercept multivariable logistic regression model was used to identify the demographics and/or work-place related potential risk factors associated with one or more morbidities. Prevalent morbidities were eye(s) complaint (45.2%), asthma/shortness of breath (7.6%), frequent sneezing and allergic rhinitis (44.3%), recurrent headache (48.3%), dizziness (9.8%), tremors (42%), and eczema/skin complaint (44.1%). Furthermore, GSWs were significantly more likely to report one or more ill-health conditions (vs. none), if they were overweight/obese (aOR 1.8; 95% CI 1.1–2.9), married (aOR 2.6; 95% CI 1.5–4.5) or on current job for more than one year (aOR 6.4; 95% CI 2.9–15.4). In conclusion, GSWs suffer from ailments of multiple organ systems and need education and facilitation for self-protection.



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Measuring Nutrition Literacy in Spanish-Speaking Latinos: An Exploratory Validation Study

Abstract

Nutrition is important for preventing and treating chronic diseases highly prevalent among Latinos, yet no tool exists for measuring nutrition literacy among Spanish speakers. This study aimed to adapt the validated Nutrition Literacy Assessment Instrument for Spanish-speaking Latinos. This study was developed in two phases: adaptation and validity testing. Adaptation included translation, expert item content review, and interviews with Spanish speakers. For validity testing, 51 participants completed the Short Assessment of Health Literacy-Spanish (SAHL-S), the Nutrition Literacy Assessment Instrument in Spanish (NLit-S), and socio-demographic questionnaire. Validity and reliability statistics were analyzed. Content validity was confirmed with a Scale Content Validity Index of 0.96. Validity testing demonstrated NLit-S scores were strongly correlated with SAHL-S scores (r = 0.52, p < 0.001). Entire reliability was substantial at 0.994 (CI 0.992–0.996) and internal consistency was excellent (Cronbach's α = 0.92). The NLit-S demonstrates validity and reliability for measuring nutrition literacy among Spanish-speakers.



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Socioeconomic and Health Profile of Haitian Immigrants in a Brazilian Amazon State

Abstract

We analyzed the sociodemographic profile, migration journey, health conditions, and health care access and utilization among recent Haitian immigrants to the Brazilian Amazon state of Mato Grosso. We conducted a cross-sectional study with a probabilistic sample of 452 Haitians. We administered a bilingual questionnaire from December 2014 to February 2015. Data were analyzed using chi square tests to evaluate differences among groups. The majority of participants were married men younger than 35 years old. They mostly came from the Haiti's Artibonite Department, living in Brazil for less than a year. Half of the participants were employed at the time of the interviews, and 81.8% relied exclusively on the Brazilian Unified Healthcare System for medical care. The overall health profile and health care access were good. Haitian migration to Brasil is a case of South–South migration driven by economic needs. Our population had good health status despite socioeconomic challenges.



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Primary health care 40 years after Alma Ata 1978: addressing new challenges in a changing society

In the 40 years since the Alma Ata Declaration the world has changed enormously. On the one hand, the world is much richer and healthier. On the other hand, those advances are unevenly spread, with growing numbers of people living precarious existences, many displaced from their homes. Health care has also changed. Advances in technology, including the advent of Big Data, coupled with adoption of evidence-based models of care have been transformational, especially for primary health care.

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The neglect of migrant oral health: setting a research agenda for Europe

Oral diseases are among the most prevalent diseases worldwide and they disproportionately affect populations from lower socioeconomic position (SEP).1 In response to this challenge, the Global Oral Health Inequalities Research Network2 and the International Centre for Oral Health Inequalities Research and Policy1 were formed to set out priorities for action and research to reduce inequalities in oral health. These initiatives, however, tend to concentrate on 'socioeconomic differences'. There is limited focus and scientific data on oral health inequalities among ethnic minority and migrant groups (henceforth migrants), especially in Europe. With 53.1 million foreign-born residents in Europe, migrants currently make up 10% of the EU's total population.3 Migrants are more likely to experience poverty and social exclusion, and studies showed poorer health outcomes of migrants compared to the host European population–even when SEP is taken into account.4

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European Public Health News

In this last European public health news of 2018, our contributors present some wise lessons to be taken in 2019. Azzopardi-Muscat points out that public health is in need of political and social marketing, using vaccination as an example. She refers to the recently published EJPH supplement on the Political analysis in public health. Jakab presents the men's health and well-being report which includes strong recommendations to create gender-responsive health systems and involve civil society wherever possible. Andriukaitis recognizes that animal health can have impact on human health stressing that the One health approach is a top priority. With the example of AMR, he presents the One health approach. Charpak and Zeegers are looking at 2019. Whilst Zeegers is introducing the European public health week, to be piloted by EUPHA in 2019, Charpak is presenting the Marseille 2019 conference, with the main theme of Building bridges of solidarity and public health. 2019 is going to be an exciting, productive and collaborative year!

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A systematic review of the indirect costs of schizophrenia in Europe

Abstract
Background
Schizophrenia is a chronic disease associated with significant and long-lasting effects on health, and it is also a social and financial burden, not only for patients but also for families, other caregivers, and the wider society. It is essential to conduct the assessment of indirect costs, to understand all the effects of the disease on society. Our aim is to gain a better understanding of the indirect costs of schizophrenia in Europe.
Methods
We conducted a comprehensive systematic literature review covering EMBASE, Medline, and PsycINFO as well as reviewing Health Technology Assessment databases from different countries. We used a qualitative research synthesis for presenting information, as most of the studies were methodologically diverse, a quantitative analysis would have been impractical.
Results
Indirect cost adjusted to inflation ranged vastly between studies included in the review from 119 Euros to 62, 034 Euros annually. The average proportion of indirect costs of total costs was 44%. Studies highlighted important cost drivers as age, gender, and disease severity, explaining the variation in costs between treatment and patient groups.
Conclusions
Regardless of the methodological heterogeneity of the reviewed studies, there was an agreement about the significance of indirect costs of schizophrenia on the society. Considering the relatively high prevalence of schizophrenia in Europe, a need for more cost of illness studies especially from Central Eastern and Southern Europe is suggested.

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Short report: persistent social inequality in poor self-rated health among adolescents in Denmark 1991–2014

Abstract
The aim was to examine trends in social inequality in poor self-rated health (SRH) among adolescents in Denmark 1991–2014. The analysis included 18 996 11–15-year-old school children from the cross-sectional Health Behaviour in School-aged Children studies in 1991, 2002, 2006, 2010 and 2014. Across the five surveys, the prevalence of poor SRH was 14.2%, remaining almost unchanged from 1991 to 2014. The proportion with poor SRH was 12.2% in high, 14.3% in middle and 17.6% in low occupational social class. This social inequality in poor SRH was persistent during the entire study period, both in terms of absolute and relative social inequality.

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Autosomal recessive Stickler syndrome resulting from a COL9A3 mutation

Stickler syndrome is a connective tissue disorder characterized by hearing loss, ocular anomalies, palatal defects, and skeletal abnormalities. The autosomal dominant form is the most common, but autosomal recessive forms have also been described. We report the second case of autosomal recessive Stickler syndrome due to homozygosity for a loss of function mutation in COL9A3, which encodes the α3 chain of type IX procollagen. The clinical features were similar to the previously described COL9A3 Stickler syndrome family, including moderate to severe sensorineural hearing loss, high myopia, and both tibial and femoral bowing at birth. Radiographs demonstrated abnormal capital femoral epiphyses and mild irregularities of the vertebral endplates. This case further establishes the phenotype associated with mutations in this gene. We suggest that loss of the α3 chain of type IX collagen results in a Stickler syndrome phenotype similar to that of the other autosomal recessive forms caused by mutations in genes encoding the α1 and α2 chains of type IX collagen.



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Next generation sequencing‐based molecular diagnosis in familial congenital cataract expands the mutational spectrum in known congenital cataract genes

Congenital cataract (CC) is a significant cause of childhood blindness worldwide. CC is a genetically heterogeneous disease because mutations in over 40 genes have been demonstrated to cause the disorder and up to 40% of cases arise from single‐gene mutations. Hence, next generation sequencing (NGS) of deoxyribonucleic acid is a suitable approach for CC molecular diagnosis. In this study, we used commercially available inherited disease NGS panels including 50 CC genes for the genetic diagnosis of 11 probands with hereditary CC. Causal variants were recognized in six families. A novel CRYGC variant, p.(Phe6Ser), was identified in two apparently unrelated families. Two additional novel variants in the crystallin genes CRYBB2 (p.[Gly149Asp]) and CRYGA (p.[Arg48Cys]) were also identified. One family carried the novel p.[Gly8_Leu11del] variant in GJA8, while another family exhibited the previously reported c.2826‐9G>A pathogenic change in EPHA2. Our results illustrate the utility of NGS for diagnosing CC in our population, and our results contribute to expand the mutational spectrum with four novel pathogenic variants in known CC genes.



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Microphthalmia is not a mandatory finding in X‐linked recessive syndromic microphthalmia caused by the recurrent BCOR variant p.Pro85Leu

Mutations in BCOR cause X‐linked dominant and X‐linked recessive forms of syndromic microphthalmia. By exome sequencing, we identified the recurrent BCOR mutation p.Pro85Leu in two brothers and their unaffected mother. While the older brother's phenotype completely fits the described phenotypic spectrum of X‐linked recessive BCOR‐associated Lenz microphthalmia syndrome, the younger brother showed developmental delay, microcephaly, and skeletal anomalies, but not the key feature of microphthalmia. In contrast to the previously published families, our findings demonstrate a large variability of BCOR‐associated, syndromic phenotypes, indicating incomplete penetrance of p.Pro85Leu with regards to microphthalmia in males.



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An additional case of Hennekam lymphangiectasia–lymphedema syndrome caused by loss‐of‐function mutation in ADAMTS3

Hennekam lymphangiectasia–lymphedema syndrome (HKLLS) is a genetically heterogeneous lymphatic dysplasia with characteristic of facial dysmorphism, neurocognitive impairments, and abnormalities of the pericardium, intestinal tract, and extremities. It is an autosomal recessive condition caused by biallelic mutations in CCBE1 (collagen‐ and calcium‐binding epidermal growth factor domain‐containing protein 1) (HKLLS1; OMIM 235510) or FAT4 (HKLLS2; OMIM 616006). CCBE1 acts via ADAMTS3 (a disintegrin and metalloprotease with thrombospondin motifs‐3 protease) to enhance vascular endothelial growth factor C signaling. There is report of one family supporting mutations in ADAMTS3 as causative for the phenotype labeled as HKLLS3. Here, we report an additional case of HKLLS that appears to be associated with homozygous nonsense mutation of ADAMTS3.



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Infant male with TARP syndrome: Review of clinical features, prognosis, and commonalities with previously reported patients

TARP syndrome (talipes equinovarus, atrial septal defect, Robin sequence, and persistent left superior vena cava) is a rare X‐linked condition. As more patients are identified through genetic testing, it is increasingly clear that the original TARP acronym does not fully describe the complete phenotypic spectrum of this syndrome. The presented patient had genetically confirmed TARP syndrome and demonstrated new findings of hydronephrosis and hemodynamically significant hypertrophic obstructive cardiomyopathy. The patient also had physical findings common with previously reported individuals with TARP syndrome in the literature but not described by the TARP acronym. These features include central nervous system dysfunction, renal abnormalities, cardiac lesions other than atrial septal defect or persistent left superior vena cava, and distal limb defects other than talipes equinovarus. By adding to the known spectrum of the TARP phenotype, this report will aid clinicians as they care for patients with this rare condition.



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Ablepharon and craniosynostosis in a patient with a localized TWIST1 basic domain substitution

The TWIST family is a group of highly conserved basic helix–loop–helix transcription factors. In humans, TWIST1 haploinsufficiency causes Saethre–Chotzen syndrome, which is characterized by craniosynostosis. Heterozygous localized TWIST1 and TWIST2 basic domain substitutions exert antimorphic effects to cause Sweeney–Cox syndrome, Barber–Say syndrome, and ablepharon‐macrostomia syndrome, respectively. Sweeney–Cox syndrome, Barber–Say syndrome, and ablepharon‐macrostomia syndrome share the facial features of ablepharon, hypertelorism, underdevelopment of the eyelids, and cheek pads adjacent to the corners of the mouth. Existence of phenotypic overlap between Saethre–Chotzen syndrome and Sweeney–Cox syndrome remains unknown. Herein, we document a male infant with the distinctive facial features of ablepharon, hypertelorism, cheek pads adjacent to the corners of the mouth, and bilateral coronal suture craniosynostosis who had a de novo heterozygous mutation in the basic domain of TWIST1, that is, c.351C>G p.Glu117Asp. The pathogenicity of this variant was supported by in silico and in vivo evidence. Our review showed that Sweeney–Cox syndrome appears to share many characteristics with Barber–Say syndrome and ablepharon‐macrostomia syndrome except for craniosynostosis, which is a cardinal feature of Saethre–Chotzen syndrome. An amino acid substitution from Glu117 to Asp, both of which are the sole members of negatively charged amino acids, resulted in a prototypic Sweeney–Cox syndrome phenotype. This suggests that any amino acid substitutions at Glu117 would likely lead to the Sweeney–Cox syndrome phenotype or lethality. The present observation suggests that a localized TWIST1 basic domain substitution, that is, p.Glu117Asp, in TWIST1 may exert a mild antimorphic effect similar to that of haploinsufficiency, leading to craniosynostosis and ablepharon.



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Extension of the mutational and clinical spectrum of SOX2 related disorders: Description of six new cases and a novel association with suprasellar teratoma

SOX2 is a transcription factor that is essential for maintenance of pluripotency and has several conserved roles in early embryonic development. Heterozygous loss‐of‐function variants in SOX2 are identified in approximately 40% of all cases of bilateral anophthalmia/micropthalmia (A/M). Increasingly SOX2 mutation‐positive patients without major eye findings, but with a range of other developmental disorders including autism, mild to moderate intellectual disability with or without structural brain changes, esophageal atresia, urogenital anomalies, and endocrinopathy are being reported, suggesting that the clinical phenotype associated with SOX2 loss is much broader than previously appreciated. In this report we describe six new cases, four of which carry novel pathogenic SOX2 variants. Four cases presented with bilateral anophthalmia in addition to extraocular involvement. Another individual presented with only unilateral anophthalmia. One individual did not have any eye findings but presented with a suprasellar teratoma in infancy and was found to have the recurrent c.70del20 mutation in SOX2 (c.70_89del, p.Asn24Argfs*65). This is this first time this tumor type has been reported in the context of a de novo SOX2 mutation. Notably, individuals with hypothalamic hamartomas and slow‐growing hypothalamo‐pituitary tumors have been reported previously, but it is still unclear how SOX2 loss contributes to their formation.



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Two unrelated individuals carrying rare mosaic deletions in TCF4 gene



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A retrospective study on sleep‐disordered breathing in Morquio‐A syndrome

Respiratory problems are common in Morquio‐A syndrome (MPS IVA) but objective data on sleep‐disordered breathing are scarce. The aim of our study was to review polygraphic (PG) findings and the need for noninvasive continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) in children with MPS IVA. A retrospective review of the clinical charts and PG of 16 consecutive children (7 boys, mean age 10.5 ± 4.2 years) with MPS IVA seen over a period of 3 years was performed. The prevalence of obstructive sleep apnea (OSA) was 69% with only five patients, all younger than 10 years old, having a normal PG. Four patients had mild OSA (apnea‐hypopnea index [AHI] ≥1.5 and <5 events/hr), three patients had moderate OSA (AHI ≥5 and <10 events/hr), and three patients had severe OSA (AHI ≥ 10 events/hr). Among the 10 patients with OSA, 3 had prior adenoidectomy ± tonsillectomy and 6 were on enzyme replacement therapy. Only one patient had a central apnea index >5 events/hr despite prior cervico‐occipital decompression. Six patients, all older than 11 years old, were started on CPAP or NIV because of severe OSA (n = 4), nocturnal hypoventilation (n = 1), or impossibility to be weaned from NIV after an acute respiratory failure (n = 1). Prevalence of OSA is high in patients with MPS IVA, underlying the importance of a systematic screening for sleep‐disordered breathing. CPAP and NIV are efficient and well accepted for treating sleep‐disordered breathing.



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First report on global fallout 236U and uranium atom ratios in soils from Hunan Province, China

Publication date: February 2019

Source: Journal of Environmental Radioactivity, Volume 197

Author(s): Yang Shao, Guosheng Yang, Diandou Xu, Masatoshi Yamada, Hirofumi Tazoe, Min Luo, Hangxin Cheng, Ke Yang, Lingling Ma

Abstract

More nuclear power plants continue to be built in China. Due to its long half-life, radiotoxicity and potential application as an environmental tracer, 236U is one of the most important artificial radionuclides deserving more study since activity data are important for risk assessment. However, the ultra-trace activity of 236U and its dilution by natural uranium isotopes make it difficult to distinguish its sources and there are only limited global fallout 236U data for present in Chinese environmental samples. In order to understand the background levels for uranium isotopes, especially 236U, and clarify their sources, inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) was applied to analyze uranium isotopes in 48 soil samples from Hunan Province, China. The 234U, 235U, 238U and 236U concentrations were measured as 9.91–33.7, 0.312–1.43, 6.63–28.7 Bq kg−1 and (1.61–21.3) × 107 atoms g−1, while, the 236U/238U, 234U/238U and 235U/238U atom ratios were (0.470–4.91) × 10−8, (5.10–9.31) × 10−5, and (7.11–7.82) × 10−3, respectively. The uranium isotopic fractionation may be due to irrigation of the agricultural lands where the samples were collected. Considering the facts that neither previous nuclear tests nor nuclear accidents had occurred in Hunan Province and the present 236U/238U atom ratios were included in the range of global fallout values in other areas, it may be concluded that 236U in soils from Hunan Province is mainly from global fallout. To the best of the authors' knowledge, the presence of global fallout 236U in soil samples from China has been confirmed for the first time, and these values may be useful as background data for risk assessment in the future.



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Acculturation and Postpartum Depression Among Immigrant Women of Arabic Descent

Abstract

Acculturation has been related to risk of postpartum depression (PPD) among immigrant women globally. The purpose of this study was to examine the relationship between acculturation and PPD symptoms among U.S. immigrant women of Arabic descent. A cross-sectional study was conducted with 115 postpartum immigrant women of Arabic descent. Women completed questionnaires including measures of acculturation [attraction to Arabic culture (AArC), attraction to American culture (AAmC), marginalization] and PPD symptoms (Edinburgh Postnatal Depression Scale—EPDS) between 1 and 12 months postpartum. Twenty-five percent of women (n = 29) had EPDS scores ≥ 10 that represent PPD symptoms. Women with higher marginalization reported more PPD symptoms (r = .25, p = .008). None of the acculturation factors correlated with PPD symptoms after adjustment for maternal sociodemographic and health characteristics. Higher education (p = .001), lower gestational age at birth (p < .05), and antenatal anxiety (p < .05) were correlated with PPD symptoms in multivariate analyses. Health care providers should identify and assess immigrant women of Arabic descent for antenatal anxiety as this may identify women at risk for development of PPD symptoms. Future studies need to examine acculturation in relation to mental health among immigrant women of Arabic descent.



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Hepatocellular carcinoma screening is associated with increased survival of patients with cirrhosis

Clinical Gastroenterology and Hepatology

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Increased mortality among patients with vs without cirrhosis and autoimmune hepatitis

Clinical Gastroenterology and Hepatology

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