Δευτέρα, 4 Δεκεμβρίου 2017

Acute effect on ambulatory blood pressure from aerobic exercise: a randomised cross-over study among female cleaners

Abstract

Purpose

High occupational physical activity (OPA) is shown to increase the risk for elevated blood pressure, cardiovascular diseases and mortality. Conversely, aerobic exercise acutely lowers the blood pressure up to 25 h post exercise. However, it is unknown if this beneficial effect also apply for workers exposed to high levels of OPA. Cleaners constitute a relevant occupational group for this investigation because of a high prevalence of OPA and cardiovascular disease. Accordingly, the objective was to investigate the acute effects on ambulatory blood pressure from a single aerobic exercise session among female cleaners.

Methods

Twenty-two female cleaners were randomised to a cross-over study with a reference and an aerobic exercise session. Differences in 24-h, work hours, leisure time, and sleep ambulatory blood pressure (ABP) were evaluated using repeated measure 2 × 2 mixed-models.

Results

After the aerobic exercise session, the 24-h systolic ambulatory blood pressure was significantly lowered by 2.4 mmHg (p < 0.01) compared to the reference session. The 24-h diastolic ABP was unaltered. During work hours, a lowered systolic ABP of 2.2 mmHg (p = 0.02) and a higher diastolic ABP of 1.5 mmHg (p = 0.03) were found after the aerobic exercise session. During leisure time, the systolic ABP was lowered by 1.7 mmHg (p = 0.04) and the diastolic ABP was unaltered. During sleep, the systolic and diastolic ABP was unaltered.

Conclusion

A single aerobic exercise session lowered 24-h systolic ABP of 2.4 mmHg. Thus, an aerobic exercise session seems to be beneficial for lowering the risk of hypertension among cleaners.



from Physiology via xlomafota13 on Inoreader http://ift.tt/2BIIpF3
via IFTTT

Robotic assisted gait as a tool for rehabilitation of individuals with spinal cord injury: a systematic review

Spinal cord injury (SCI) is characterized by a total or partial deficit of sensory and motor pathways. Impairments of this injury compromise muscle recruitment and motor planning, thus reducing functional capa...

from Rehabilitation via xlomafota13 on Inoreader http://ift.tt/2zMy1un
via IFTTT

Ethical Responsibilities of the Authors



from Physiology via xlomafota13 on Inoreader http://ift.tt/2BIjzoy
via IFTTT

Nasotracheal intubation through pharyngeal flap after pharyngeal flap construction.

Nasotracheal intubation through pharyngeal flap after pharyngeal flap construction.

J Clin Anesth. 2017 Nov 29;44:121-122

Authors: Takaishi K, Kawahito S, Fujiwara S, Kitahata H

PMID: 29197265 [PubMed - as supplied by publisher]



from Anaesthesiology via xlomafota13 on Inoreader http://ift.tt/2kkOumT
via IFTTT

Laparoscopic splenopexy for wandering spleen, a video demonstration of technique by encircling the spleen with polyglactin 910 woven mesh

Abstract

Background

Wandering spleen is a rare clinical entity caused by absence of the spleen's peritoneal attachments, allowing the spleen to move freely within the peritoneal cavity [1]. This disease is most commonly seen in children and young women [1, 2]. Affected individuals are predisposed to complications including splenic torsion, splenic infarction, and pancreatic necrosis [3, 4]. Patients may present with constipation, an abdominal mass, swelling, or acute abdominal pain if splenic torsion has occurred [4]. Wandering spleen is difficult to diagnose without imaging, as symptoms are non-specific or may be absent. Imaging studies to confirm the diagnosis may include computed tomography (CT) scan or duplex ultrasonography [5]. Definitive management of a wandering spleen is primarily surgical [2]. Splenectomy is the preferred treatment in patients who present with an acute splenic infarction [2, 6]. Splenopexy, however, is first line treatment for patients with a non-infarcted wandering spleen [2, 7, 8].

Case presentation

In this video, we present a case of an 11 year old male with a symptomatic wandering spleen who was treated at our institution with laparoscopic splenopexy. The patient had a history of arthrogryposis multiplex congenita and presented with recurrent, episodic abdominal pain, nausea, and vomiting. The diagnosis was confirmed by CT scan which demonstrated the spleen in the right lower quadrant. We performed laparoscopic splenopexy by encircling the spleen with polyglactin 910 woven mesh and attaching the mesh to the left lateral abdominal wall with absorbable tacks.

Discussion

Our surgical technique for splenopexy was successful and the patient returned home on postoperative day four. No significant complications occurred. This video demonstrates this technique and highlights the key steps. Splenopexy by encircling the spleen with polyglactin 910 mesh is feasible, preserves splenic function, and can be performed with standard laparoscopic equipment. Tacks or transfascial sutures are a potential option for securing mesh.



from Endoscopy via xlomafota13 on Inoreader http://ift.tt/2ByiZsz
via IFTTT

Endoscopic submucosal dissection for laterally spreading tumors involving the appendiceal orifice

Abstract

Background

Since the endoscopic resection of laterally spreading tumors (LSTs) involving the appendiceal orifice remains technically difficult, such lesions are usually treated by surgical resection. However, with recent advances in endoscopic devices, endoscopic submucosal dissection (ESD) has become feasible and may be safely performed even for lesions involving the appendiceal orifice. Therefore, in order to assess the validity of endoscopic treatment for such lesions, we retrospectively evaluated the safety and efficacy of ESD.

Methods

A total of 30 patients with LSTs extending to within 10 mm of the appendiceal orifice (Group AO) and 122 patients with cecal LSTs located away from the appendiceal orifice (Group C) who were treated between December 2011 and September 2015 were retrospectively enrolled in the present study. The indications for ESD were determined by the preoperative endoscopic diagnosis made on the basis of Kudo's pit pattern classification. Based on these preoperative endoscopic diagnoses, 8 of the 30 enrolled patients underwent surgical resection as the initial treatment, because the tumor showed deep invasion beyond the orifice and/or a VN pit pattern was visible. The treatment outcomes (en bloc R0 resection rates, tumor size, procedure time, and complication rates) were compared between the two groups.

Results

The sensitivity and specificity for the cancer diagnosis were 81.8 and 94.7%, respectively. There was no significant difference in the en bloc R0 resection rate between Group AO and Group C (90.9 vs. 95.9%, P = 0.23). Furthermore, there were also no differences in the mean tumor size (30.0 ± 20.8 vs. 34.9 ± 14.5 mm, P = 0.17) or mean OR time (55.0 ± 39.2 vs. 58.9 ± 48.2 min P = 0.72) between the two groups. One case from Group AO (4.5%) was complicated by a perforation, which was successfully managed endoscopically.

Conclusions

Although proficiency in endoscopic techniques is required, our results indicate that LSTs involving the appendiceal orifice can be successfully treated by ESD.



from Endoscopy via xlomafota13 on Inoreader http://ift.tt/2jdV773
via IFTTT

Liquid antiadhesive agents for intraperitoneal hernia repair procedures: Artiss ® compared to CoSeal ® and Adept ® in an IPOM rat model

Abstract

Background

Adhesion formation remains an important issue in hernia surgery. Liquid agents were developed for easy and versatile application, especially in laparoscopy. The aim of this study was to compare the antiadhesive effect of fibrin sealant (FS, Artiss®), Icodextrin (ID, Adept®) and Polyethylene glycol (PEG, CoSeal®) alone and in combination and to evaluate the resulting effect on tissue integration of the mesh.

Methods

A total of 56 Sprague–Dawley rats were operated in open IPOM technique. A middleweight polypropylene mesh of 2 × 2 cm size was implanted and covered with 1: FS, 2: ID, 3: PEG, 4: FS + ID, 5: FS + PEG, 6: PEG + ID, 7: control group, uncovered mesh (n = 8 per treatment/control). Observation period was 30 days. Macroscopic and histological evaluation was performed.

Results

Severe adhesions were found in group 2 (ID), group 6 (PEG + ID) and the controls. Best results were achieved with FS alone or FS + ID. Mesh integration in the treatment groups was reduced in comparison with the control group. This is a new finding possibly relevant for the outcome of intraperitoneal mesh repair. Group 6 (PEG + ID) showed an impairment of tissue integration with <50 % of the mesh surface in seven samples.

Conclusion

FS alone and in combination with ID yielded excellent adhesion prevention. ID alone did not show significant adhesion prevention after 30 days. Tissue integration of FS-covered meshes was superior to ID or PEG alone or combined. PEG did show adhesion prevention comparable to FS but evoked impaired tissue integration. So Artiss® is among the most potent antiadhesive agents in IPOM repair.



from Endoscopy via xlomafota13 on Inoreader http://ift.tt/2BxEEB7
via IFTTT

Study of self-expandable metallic stent placement intraluminal 125 I seed strands brachytherapy of malignant biliary obstruction

Abstract

Objective

To evaluate the safety and efficacy of self-expandable metallic stent placement combined with or without intraluminal 125I seed strands brachytherapy in patients with malignant biliary obstruction.

Methods

Participants were randomly assigned to receive treatment with a self-expandable metallic stent (SEMS) placement combined with intraluminal 125I seed strands brachytherapy (brachytherapy group) or a SEMS without brachytherapy (control group). The outcomes were measured in terms of technical success, clinical success, stent patency, complications related to the procedure, and patient survival. A P value of less than 0.05 indicated a significant difference.

Results

There were no significant differences in technical and clinical success between brachytherapy and control group (100 vs. 100%–100 vs. 93.3%). During the median 273.4 ± 154.6 days follow-up time, the median stent patency time in the brachytherapy group was longer than those in the control group (368.0 ± 42.4 vs. 220.0 ± 34.8 days), and the duration of survival in the brachytherapy groups was higher than those in the control group (355.0 ± 71.5 vs. 209.0 ± 17.2 days). There were no significant differences in the complications between the two groups.

Conclusions

SEMS placement combined with intraluminal 125I seed strands brachytherapy are feasible and effective for malignant biliary obstruction, and seems to prolong the stent patency and survival time.



from Endoscopy via xlomafota13 on Inoreader http://ift.tt/2jdUXMZ
via IFTTT

Psychopathology and Associated Risk Factors Among Forcibly Displaced Syrian Children and Adolescents

Abstract

More than half of the 2.7 million registered Syrian refugees in Turkey are under 18 years of age. This study investigates prevalence of psychopathology and associated risk factors in refugee children in Turkey. Of a total of 218 children aged 9–15 years, 56.2% lost someone important to them, 55.1% saw dead or wounded people, 70.4% witnessed explosions or gun battles, 42.5% witnessed people being tortured and 25.6% personally experienced cruelty/torture during war. Prevalence of PTSD was 18.3% and that of anxiety-related disorders were as high as 69.0%. Death of an important person (p = .032) and male gender (p = .040) were associated with PTSD; whilst exposure to cruelty or torture (p = .014) and increasing duration of refuge (p = .042) were significantly associated with development of anxiety disorders. Findings of the present study reveals existence of the expected but unspoken mental health needs among the Syrian children in Turkey.



from Health via xlomafota13 on Inoreader http://ift.tt/2je0dQG
via IFTTT

EUS-Guided Pancreatic Duct Puncture for Difficult Cannulation of Stenosed Pancreaticojejunostomy



from Gastroenterology via xlomafota13 on Inoreader http://ift.tt/2AP2cF8
via IFTTT

Made in N o r w a y . . ! Just like Asmund Laerdal !

hqdefault.jpg

What is the future made of ? ( Hint: "Free" Healt-Care from pregnancy - Grave. "Free" Edukation, From pre school to universety. Laerdal medical is a Norwegian company, nothing to do with Sweeden ! ExEMTNor

from EMS via xlomafota13 on Inoreader http://ift.tt/2AoEted
via IFTTT

“Sex Will Make Your Fingers Grow Thin and Then You Die”: The Interplay of Culture, Myths, and Taboos on African Immigrant Mothers’ Perceptions of Reproductive Health Education with Their Daughters Aged 10–14 Years

Abstract

This paper examines the convergence of culture, myths, and taboos surrounding reproductive health issues African immigrant women, living in the United States, learned during childhood in their countries of origin. We also discuss how mothers' perceptions of reproductive health education (RHE) influenced the education of their own daughters aged 10–14 years. This was a qualitative descriptive study. Data were collected via interviews and demographic survey. The sample size was 20 African immigrant mothers living in a mid-sized city in the U.S. Interviews were transcribed verbatim. Qualitative data was analyzed using qualitative content analysis. Myths and taboos related to menstruation, sexual intercourse, pregnancy, and HIV/AIDS were reported by the women interviewed. Discussion of these issues was largely taboo, and most myths the mothers learned growing up pertained to sexual intercourse, pregnancy prevention, and pregnancy termination using non-hormonal ingested substances. Myths and taboos about sexual issues are widespread in Africa and are propagated to control sexual behavior, especially that of unmarried people, particularly women. By examining these myths and taboos, we are able to somewhat contextualize the mothers' immigrant experience regarding RHE. Although myths were reported, the majority of mothers did not appear to believe them. The most significant taboo reported was sexual intercourse. This in turn led to mothers' overemphasis on abstinence for their daughters. It is also noteworthy that this sample contained mainly African women who overall were highly educated, spoke English, and could adequately navigate life in the U.S. It is unclear what the results would be if we were to examine African immigrant women with less achievements in these areas.



from Health via xlomafota13 on Inoreader http://ift.tt/2ij9whr
via IFTTT

Genetic Variation and Gene Expression Levels of Tight Junction Genes Indicates Relationships Between PTEN as well as MAGI1 and Microscopic Colitis

Abstract

Background and Aim

Microscopic colitis (MC) has been associated with increased paracellular permeability. Therefore, we aimed to investigate potential associations between MC and several genes encoding tight junction (TJ) proteins reported to interact with each other.

Methods

The association between MC and single nucleotide polymorphisms (SNP; n = 63) within TJ genes (F11R, MAGI1, MAGI2, MAGI3, PARD3, PTEN, and TJP1) were investigated in a case–control study (n MC patients = 104 and n controls = 423). The genes that exhibited an association with MC were further investigated for gene expression related to genotype, MC phenotype, and gender using colonic biopsies from MC patients (n = 25) and controls (n = 58).

Results

Based on the number of investigated genes and after correction for multiple testing, an association was detected between a SNP marker in PTEN (rs1234224) and both MC overall (OR = 1.70, 95% CI 1.23–2.34, p = 0.001) and collagenous colitis (CC; OR = 1.79, 95% CI 1.22–2.62, p = 0.003). Further, SNP markers in MAGI1 (rs17417230) and F11R (rs790055) were associated with MC overall (OR = 1.58, 95% CI 1.14–2.19, p = 0.006) and with CC (OR = 2.58, 95% CI 1.27–5.25, p = 0.007), respectively. However, none of the associated SNPs contributed markedly to the expression of the respective genes. Nonetheless, decreased MAGI1 (p = 3.47 × 10−4) and PTEN (p = 0.004) expression was associated with lymphocytic colitis (LC) and CC, respectively, compared to controls.

Conclusions

Decreased expression of PTEN and MAGI1 in the colonic mucosa might contribute to the pathogenesis of MC and its sub-phenotypes. Furthermore, our study indicates that genetic variants of TJ components are predisposing factors in the etiology of MC. Finally, F11R, MAGI1, and PTEN are new candidate genes that exhibit an association with MC.



from Gastroenterology via xlomafota13 on Inoreader http://ift.tt/2AuEbAm
via IFTTT

Made in N o r w a y . . ! Just like Asmund Laerdal !

hqdefault.jpg

What is the future made of ? ( Hint: "Free" Healt-Care from pregnancy - Grave. "Free" Edukation, From pre school to universety. Laerdal medical is a Norwegian company, nothing to do with Sweeden ! ExEMTNor

from EMS via xlomafota13 on Inoreader http://ift.tt/2AoEted
via IFTTT

Made in N o r w a y . . ! Just like Asmund Laerdal !

hqdefault.jpg

What is the future made of ? ( Hint: "Free" Healt-Care from pregnancy - Grave. "Free" Edukation, From pre school to universety. Laerdal medical is a Norwegian company, nothing to do with Sweeden ! ExEMTNor

from EMS via xlomafota13 on Inoreader http://ift.tt/2AoEted
via IFTTT

Made in N o r w a y . . ! Just like Asmund Laerdal !

hqdefault.jpg

What is the future made of ? ( Hint: "Free" Healt-Care from pregnancy - Grave. "Free" Edukation, From pre school to universety. Laerdal medical is a Norwegian company, nothing to do with Sweeden ! ExEMTNor

from EMS via xlomafota13 on Inoreader http://ift.tt/2AoEted
via IFTTT

Transcription: Shedding light on alternative promoter selection



from Genetics via xlomafota13 on Inoreader http://ift.tt/2mIKE7Q
via IFTTT

Los Angeles rolls out 911 texting service

The new system is meant to allow people who are hard of hearing, speech-impaired or unable to talk safely on the phone to connect with emergency services

from EMS via xlomafota13 on Inoreader http://ift.tt/2jMtoJW
via IFTTT

Digitized evaluation of speech intelligibility using vowels in maxillectomy patients

Abstract

Background

Among the functional disabilities that patients face following maxillectomy, speech impairment is a major factor influencing quality of life. Proper rehabilitation of speech, which may include prosthodontic and surgical treatment and speech therapy, requires accurate evaluation of speech intelligibility (SI). A simple, less time-consuming yet accurate evaluation is desirable both for maxillectomy patients and the various clinicians providing maxillofacial treatment.

Objective

This study sought to determine the utility of digital acoustic analysis of vowels for the prediction of SI in maxillectomy patients, based on a comprehensive understanding of speech production in the vocal tract of maxillectomy patients and its perception.

Methods

Speech samples were collected from 33 male maxillectomy patients (mean age 57.4 years) in two conditions, without and with a maxillofacial prosthesis, and formant data for the vowels /a/, /e/, /i/, /o/, and /u/ were calculated based on linear predictive coding. The frequency range of formant 2 (F2) was determined by differences between the minimum and maximum frequency. An SI test was also conducted to reveal the relationship between SI score and F2 range. Statistical analyses were applied.

Results

F2 range and SI score were significantly different between the two conditions without and with a prosthesis (both p < 0.0001). F2 range was significantly correlated with SI score in both the conditions (Spearman's r = 0.843, p < 0.0001; r = 0.832, p < 0.0001, respectively).

Conclusion

These findings indicate that calculating the F2 range from 5 vowels has clinical utility for the prediction of SI after maxillectomy.

This article is protected by copyright. All rights reserved.



from Rehabilitation via xlomafota13 on Inoreader http://ift.tt/2jdfHEy
via IFTTT

The relationship between jaw-opening force and the cross-sectional area of the suprahyoid muscles in healthy elderly

Abstract

We conducted a clinical cross-sectional study to examine the relationship between jaw-opening force and the cross-sectional area of the suprahyoid muscles and whole skeletal muscle mass. Subjects were healthy 39 males and 51 females without dysphagia and sarcopenia, aged 65 years and older. Jaw-opening force was measured three times using a jaw-opening sthenometer; the maximal of these three was taken as the measurement value. The cross-sectional area of the geniohyoid and anterior belly of the digastric muscles was evaluated using ultrasonography. The skeletal muscle mass index, gait speed, and grip strength were evaluated according to the diagnostic criteria of the Asian Working Group for Sarcopenia. For each sex, a multiple regression analysis determined the factors that affect jaw-opening force. Jaw-opening force was associated with the cross-sectional area of the geniohyoid muscle in males (regression coefficient [β] = 0.441, 95% confidence interval [CI] = 14.28–56.09) and females (β = 0.28, 95% CI = 3.10–54.57). Furthermore, in females only, jaw-opening force was associated with the skeletal muscle mass index (β = 0.40, 95% CI = 3.67–17.81). In contrast, jaw-opening force was not associated with the cross-sectional area of the anterior belly of the digastric muscle in either sex. In healthy elderly males and females, jaw-opening force was positively associated with the cross-sectional area of the geniohyoid muscle. However, the jaw-opening force was positively associated with the skeletal muscle mass index only in females.

This article is protected by copyright. All rights reserved.



from Rehabilitation via xlomafota13 on Inoreader http://ift.tt/2BHyQpx
via IFTTT

Validation of the Pain Resilience Scale in Chinese-speaking patients with TMD pain

Abstract

To validate of the Pain Resilience Scale (PRS) for use in Chinese patients with temporomandibular disorders (TMD) pain. According to international guidelines, the original PRS was first translated and cross-culturally adapted to formulate the Chinese version of PRS (PRS-C). A total of 152 patients with TMD pain were recruited to complete series of questionnaires. Reliability of the PRS-C was investigated using internal consistency and test-retest reliability. Validity of the PRS-C was calculated using cross-cultural validity and convergent validity. Cross-cultural validity was evaluated by examining the confirmatory factor analysis (CFA). And convergent validity was examined through correlating the PRS-C scores with scores of two commonly used pain-related measures (the Connor-Davidson Resilience Scale (CD-RISC) and the Tampa Scale for Kinesiophobia for Temporomandibular Disorders (TSK-TMD)). The PRS-C had a high internal consistency (Cronbach's alpha = 0.92) and good test-retest reliability ((intraclass correlation coefficient (ICC) = 0.81). The CFA supported a two-factor model for the PRS-C with acceptable fit to the data. The fit indices were Chi-Square/DF=2.21, GFI=0.91, TLI=0.97, CFI=0.98, RMSEA= 0.08. As regards convergent validity, the PRS-C evidenced moderate-to-good relationships with the CD-RISC and the TSK-TMD. The PRS-C shows good psychometric properties and could be considered as a reliable and valid measure to evaluate pain-related resilience in patients with TMD pain.

This article is protected by copyright. All rights reserved.



from Rehabilitation via xlomafota13 on Inoreader http://ift.tt/2kiXoRM
via IFTTT

Influence of removable prostheses on mastication in elderly subjects with rheumatoid arthritis Mastication in elders with rheumatoid arthritis

Abstract

Background

Rheumatoid arthritis (RA) is a prevalent disease in the elderly population, and it may affect the temporomandibular joint (TMJ) and the stomatognathic system

Objective

This study evaluated masticatory function in elderly patients with RA before and after oral rehabilitation with removable prostheses

Methods

Forty-five elders with partial or total edentulism who were using unsatisfactory removable prostheses were selected and assigned to three groups: RA with TMJ involvement, RA without TMJ involvement, and healthy controls. Masticatory function was assessed in terms of masticatory performance (MP) and maximum bite force (MBF). The former was determined by the sieving method and the latter was measured by pressure sensors placed in the bilateral molar regions. The variables were first evaluated in elderly subjects wearing unsatisfactory prostheses, and re-assessed after participants had received new removable prostheses. Comparisons between groups and among time points were performed with analysis of variance for repeated measures and the Tukey–Kramer test (P < 0.05).

Results

Comparison among groups showed decreased MP in elders with RA before new prosthesis insertion (P < 0.05). Irrespective of TMJ involvement, MP improved after treatment in subjects with RA. RA groups also showed decreased MBF (P < 0.05), which improved after new prosthesis insertion.

Conclusion

RA might impair masticatory function, and well-fitted removable prosthesis insertion might be very beneficial in elders with RA.

This article is protected by copyright. All rights reserved.



from Rehabilitation via xlomafota13 on Inoreader http://ift.tt/2BHYCdg
via IFTTT

G3 Reviewer Index 2017



from Genetics via xlomafota13 on Inoreader http://ift.tt/2AVdwQx
via IFTTT

APC/CFZR-1 Controls SAS-5 Levels To Regulate Centrosome Duplication in Caenorhabditis elegans

As the primary microtubule-organizing center, centrosomes play a key role in establishing mitotic bipolar spindles that secure correct transmission of genomic content. For the fidelity of cell division, centrosome number must be strictly controlled by duplicating only once per cell cycle. Proper levels of centrosome proteins are shown to be critical for normal centrosome number and function. Overexpressing core centrosome factors leads to extra centrosomes, while depleting these factors results in centrosome duplication failure. In this regard, protein turnover by the ubiquitin-proteasome system provides a vital mechanism for the regulation of centrosome protein levels. Here, we report that FZR-1, the Caenorhabditis elegans homolog of Cdh1/Hct1/Fzr, a coactivator of the anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase, functions as a negative regulator of centrosome duplication in the C. elegans embryo. During mitotic cell division in the early embryo, FZR-1 is associated with centrosomes and enriched at nuclei. Loss of fzr-1 function restores centrosome duplication and embryonic viability to the hypomorphic zyg-1(it25) mutant, in part, through elevated levels of SAS-5 at centrosomes. Our data suggest that the APC/CFZR-1 regulates SAS-5 levels by directly recognizing the conserved KEN-box motif, contributing to proper centrosome duplication. Together, our work shows that FZR-1 plays a conserved role in regulating centrosome duplication in C. elegans.



from Genetics via xlomafota13 on Inoreader http://ift.tt/2A28lOE
via IFTTT

Repression of Middle Sporulation Genes in Saccharomyces cerevisiae by the Sum1-Rfm1-Hst1 Complex Is Maintained by Set1 and H3K4 Methylation

The conserved yeast histone methyltransferase Set1 targets H3 lysine 4 (H3K4) for mono, di, and trimethylation and is linked to active transcription due to the euchromatic distribution of these methyl marks and the recruitment of Set1 during transcription. However, loss of Set1 results in increased expression of multiple classes of genes, including genes adjacent to telomeres and middle sporulation genes, which are repressed under normal growth conditions because they function in meiotic progression and spore formation. The mechanisms underlying Set1-mediated gene repression are varied, and still unclear in some cases, although repression has been linked to both direct and indirect action of Set1, associated with noncoding transcription, and is often dependent on the H3K4me2 mark. We show that Set1, and particularly the H3K4me2 mark, are implicated in repression of a subset of middle sporulation genes during vegetative growth. In the absence of Set1, there is loss of the DNA-binding transcriptional regulator Sum1 and the associated histone deacetylase Hst1 from chromatin in a locus-specific manner. This is linked to increased H4K5ac at these loci and aberrant middle gene expression. These data indicate that, in addition to DNA sequence, histone modification status also contributes to proper localization of Sum1. Our results also show that the role for Set1 in middle gene expression control diverges as cells receive signals to undergo meiosis. Overall, this work dissects an unexplored role for Set1 in gene-specific repression, and provides important insights into a new mechanism associated with the control of gene expression linked to meiotic differentiation.



from Genetics via xlomafota13 on Inoreader http://ift.tt/2A3Al4k
via IFTTT

rSalvador: An R Package for the Fluctuation Experiment

The past few years have seen a surge of novel applications of the Luria-Delbrück fluctuation assay protocol in bacterial research. Appropriate analysis of fluctuation assay data often requires computational methods that are unavailable in the popular web tool FALCOR. This paper introduces an R package named rSalvador to bring improvements to the field. The paper focuses on rSalvador's capabilities to alleviate three kinds of problems found in recent investigations: (i) resorting to partial plating without properly accounting for the effects of partial plating; (ii) conducting attendant fitness assays without incorporating mutants' relative fitness in subsequent data analysis; and (iii) comparing mutation rates using methods that are in general inapplicable to fluctuation assay data. In addition, the paper touches on rSalvador's capabilities to estimate sample size and the difficulties related to parameter nonidentifiability.



from Genetics via xlomafota13 on Inoreader http://ift.tt/2A294iR
via IFTTT

Dissecting Nucleosome Function with a Comprehensive Histone H2A and H2B Mutant Library

Using a comprehensive library of histone H2A and H2B mutants, we assessed the biological function of each amino acid residue involved in various stress conditions including exposure to different DNA damage-inducing reagents, different growth temperatures, and other chemicals. H2B N- and H2A C-termini were critical for maintaining nucleosome function and mutations in these regions led to pleiotropic phenotypes. Additionally, two screens were performed using this library, monitoring heterochromatin gene silencing and genome stability, to identify residues that could compromise normal function when mutated. Many distinctive regions within the nucleosome were revealed. Furthermore, we used the barcode sequencing (bar-seq) method to profile the mutant composition of many libraries in one high-throughput sequencing experiment, greatly reducing the labor and increasing the capacity. This study not only demonstrates the applications of the versatile histone library, but also reveals many previously unknown functions of histone H2A and H2B.



from Genetics via xlomafota13 on Inoreader http://ift.tt/2ATX4A2
via IFTTT

Modulation of Global Transcriptional Regulatory Networks as a Strategy for Increasing Kanamycin Resistance of the Translational Elongation Factor-G Mutants in Escherichia coli

Evolve and resequence experiments have provided us a tool to understand bacterial adaptation to antibiotics. In our previous work, we used short-term evolution to isolate mutants resistant to the ribosome targeting antibiotic kanamycin, and reported that Escherichia coli develops low cost resistance to kanamycin via different point mutations in the translation Elongation Factor-G (EF-G). Furthermore, we had shown that the resistance of EF-G mutants could be increased by second site mutations in the genes rpoD/cpxA/topA/cyaA. Mutations in three of these genes had been discovered in earlier screens for aminoglycoside resistance. In this work, we expand our understanding of these second site mutations, the goal being to understand how these mutations affect the activities of the mutated gene products to confer resistance. We show that the mutation in cpxA most likely results in an active Cpx stress response. Further evolution of an EF-G mutant in a higher concentration of kanamycin than what was used in our previous experiments identified the cpxA locus as a primary target for a significant increase in resistance. The mutation in cyaA results in a loss of catalytic activity and probably results in resistance via altered CRP function. Despite a reduction in cAMP levels, the CyaAN600Y mutant has a transcriptome indicative of increased CRP activity, pointing to an unknown role for CyaA and / or cAMP in gene expression. From the transcriptomes of double and single mutants, we describe the epistasis between the mutation in EF-G and these second site mutations. We show that the large scale transcriptomic changes in the topoisomerase I (FusAA608E-TopAS180L) mutant likely result from increased negative supercoiling in the cell. Finally, genes with known roles in aminoglycoside resistance were present among the misregulated genes in the mutants.



from Genetics via xlomafota13 on Inoreader http://ift.tt/2A3Ad4Q
via IFTTT

Transcriptomic Analysis of Octanoic Acid Response in Drosophila sechellia Using RNA-Sequencing

The dietary specialist fruit fly Drosophila sechellia has evolved to specialize on the toxic fruit of its host plant Morinda citrifolia. Toxicity of Morinda fruit is primarily due to high levels of octanoic acid (OA). Using RNA interference (RNAi), prior work found that knockdown of Osiris family genes Osiris 6 (Osi6), Osi7, and Osi8 led to increased susceptibility to OA in adult D. melanogaster flies, likely representing genes underlying a Quantitative Trait Locus (QTL) for OA resistance in D. sechellia. While genes in this major effect locus are beginning to be revealed, prior work has shown at least five regions of the genome contribute to OA resistance. Here, we identify new candidate OA resistance genes by performing differential gene expression analysis using RNA-sequencing (RNA-seq) on control and OA-exposed D. sechellia flies. We found 104 significantly differentially expressed genes with annotated orthologs in D. melanogaster, including six Osiris gene family members, consistent with previous functional studies and gene expression analyses. Gene ontology (GO) term enrichment showed significant enrichment for cuticle development in upregulated genes and significant enrichment of immune and defense responses in downregulated genes, suggesting important aspects of the physiology of D. sechellia that may play a role in OA resistance. In addition, we identified five candidate OA resistance genes that potentially underlie QTL peaks outside of the major effect region, representing promising new candidate genes for future functional studies.



from Genetics via xlomafota13 on Inoreader http://ift.tt/2AUf0KP
via IFTTT

Understanding microRNA Regulation Involved in the Metamorphosis of the Veined Rapa Whelk (Rapana venosa)

The veined rapa whelk (Rapana venosa) is widely consumed in China. Nevertheless, it preys on oceanic bivalves, thereby reducing this resource worldwide. Its larval metamorphosis comprises a transition from pelagic to benthic form, which involves considerable physiological and structural changes and has vital roles in its natural populations and commercial breeding. Thus, understanding the endogenous microRNAs (miRNAs) that drive metamorphosis is of great interest. This is the first study to use high-throughput sequencing to examine the alterations in miRNA expression that occur during metamorphosis in a marine gastropod. A total of 195 differentially expressed miRNAs were obtained. Sixty-five of these were expressed during the transition from precompetent to competent larvae. Thirty-three of these were upregulated and the others were downregulated. Another 123 miRNAs were expressed during the transition from competent to postlarvae. Ninety-six of these were upregulated and the remaining 27 were downregulated. The expression of miR-276-y, miR-100-x, miR-183-x, and miR-263-x showed a >100-fold change during development, while the miR-242-x and novel-m0052-3p expression levels changed over 3000-fold. Putative target gene coexpression, gene ontology, and pathway analyses suggest that these miRNAs play important parts in cell proliferation, migration, apoptosis, metabolic regulation, and energy absorption. Twenty miRNAs and their target genes involved in ingestion, digestion, cytoskeleton, cell adhesion, and apoptosis were identified. Nine of them were analyzed with real-time polymerase chain reaction (PCR), which showed an inverse correlation between the miRNAs and their relative expression levels. Our data elucidate the role of miRNAs in R. venosa metamorphic transition and serve as a solid basis for further investigations into regulatory mechanisms of gastropod metamorphosis.



from Genetics via xlomafota13 on Inoreader http://ift.tt/2A0Z7C6
via IFTTT

Caenorhabditis elegans BUB-3 and SAN-1/MAD3 Spindle Assembly Checkpoint Components Are Required for Genome Stability in Response to Treatment with Ionizing Radiation

Relatively little is known about the cross-talk between the spindle assembly checkpoint and the DNA damage response, especially in multicellular organisms. We performed a Caenorhabditis elegans forward genetic screen to uncover new genes involved in the repair of DNA damage induced by ionizing radiation. We isolated a mutation, gt2000, which confers hypersensitivity to ionizing radiation and showed that gt2000 introduces a premature stop in bub-3. BUB-3 is a key component of the spindle assembly checkpoint. We provide evidence that BUB-3 acts during development and in the germline; irradiated bub-3(gt2000) larvae are developmentally retarded and form abnormal vulvae. Moreover, bub-3(gt2000) embryos sired from irradiated worms show increased levels of lethality. Both bub-3 and san-1 (the C. elegans homolog of MAD3) deletion alleles confer hypersensitivity to ionizing radiation, consistent with the notion that the spindle assembly checkpoint pathway is required for the DNA damage response. bub-3(gt2000) is moderately sensitive to the cross-linking drug cisplatin but not to ultraviolet light or methyl methanesulfonate. This is consistent with a role in dealing with DNA double-strand breaks and not with base damage. Double mutant analysis revealed that bub-3 does not act within any of the three major pathways involved in the repair of double-strand breaks. Finally, the cdc-20 gain-of-function mutant cdc-20/fzy-1(av15), which is refractory to the cell cycle delay conferred by the spindle checkpoint, showed phenotypes similar to bub-3 and san-1 mutants. We speculate that BUB-3 is involved in the DNA damage response through regulation of cell cycle timing.



from Genetics via xlomafota13 on Inoreader http://ift.tt/2ATWTVo
via IFTTT

SID-1 Domains Important for dsRNA Import in Caenorhabditis elegans

In the nematode Caenorhabditis elegans, RNA interference (RNAi) triggered by double-stranded RNA (dsRNA) spreads systemically to cause gene silencing throughout the organism and its progeny. We confirm that Caenorhabditis nematode SID-1 orthologs have dsRNA transport activity and demonstrate that the SID-1 paralog CHUP-1 does not transport dsRNA. Sequence comparison of these similar proteins, in conjunction with analysis of loss-of-function missense alleles, identifies several conserved 2–7 amino acid microdomains within the extracellular domain (ECD) that are important for dsRNA transport. Among these missense alleles, we identify and characterize a sid-1 allele, qt95, which causes tissue-specific silencing defects most easily explained as a systemic RNAi export defect. However, we conclude from genetic and biochemical analyses that sid-1(qt95) disrupts only import, and speculate that the apparent export defect is caused by the cumulative effect of sequentially impaired dsRNA import steps. Thus, consistent with previous studies, we fail to detect a requirement for sid-1 in dsRNA export, but demonstrate for the first time that SID-1 functions in the intestine to support environmental RNAi (eRNAi).



from Genetics via xlomafota13 on Inoreader http://ift.tt/2AUhuJ2
via IFTTT

Molecular Basis of Overdominance at a Flower Color Locus

Single-gene overdominance is one of the major mechanisms proposed to explain heterosis (i.e., hybrid vigor), the phenomenon that hybrid offspring between two inbred lines or varieties show superior phenotypes to both parents. Although sporadic examples of single-gene overdominance have been reported over the decades, the molecular nature of this phenomenon remains poorly understood and it is unclear whether any generalizable principle underlies the various cases. Through bulk segregant analysis, chemical profiling, and transgenic experiments, we show that loss-of-function alleles of the FLAVONE SYNTHASE (FNS) gene cause overdominance in anthocyanin-based flower color intensity in the monkeyflower species Mimulus lewisii. FNS negatively affects flower color intensity by competing with the anthocyanin biosynthetic enzymes for the same substrates, yet positively affects flower color intensity by producing flavones, the colorless copigments required for anthocyanin stabilization, leading to enhanced pigmentation in the heterozyote (FNS/fns) relative to both homozygotes (FNS/FNS and fns/fns). We suggest that this type of antagonistic pleiotropy (i.e., alleles with opposing effects on different components of the phenotypic output) might be a general principle underlying single-gene overdominance.



from Genetics via xlomafota13 on Inoreader http://ift.tt/2ATWMsW
via IFTTT

A Predictive Model for Time-to-Flowering in the Common Bean Based on QTL and Environmental Variables

The common bean is a tropical facultative short-day legume that is now grown in tropical and temperate zones. This observation underscores how domestication and modern breeding can change the adaptive phenology of a species. A key adaptive trait is the optimal timing of the transition from the vegetative to the reproductive stage. This trait is responsive to genetically controlled signal transduction pathways and local climatic cues. A comprehensive characterization of this trait can be started by assessing the quantitative contribution of the genetic and environmental factors, and their interactions. This study aimed to locate significant QTL (G) and environmental (E) factors controlling time-to-flower in the common bean, and to identify and measure G E interactions. Phenotypic data were collected from a biparental [Andean x Mesoamerican] recombinant inbred population (F11:14, 188 genotypes) grown at five environmentally distinct sites. QTL analysis using a dense linkage map revealed 12 QTL, five of which showed significant interactions with the environment. Dissection of G E interactions using a linear mixed-effect model revealed that temperature, solar radiation, and photoperiod play major roles in controlling common bean flowering time directly, and indirectly by modifying the effect of certain QTL. The model predicts flowering time across five sites with an adjusted r-square of 0.89 and root-mean square error of 2.52 d. The model provides the means to disentangle the environmental dependencies of complex traits, and presents an opportunity to identify in silico QTL allele combinations that could yield desired phenotypes under different climatic conditions.



from Genetics via xlomafota13 on Inoreader http://ift.tt/2A3zXCU
via IFTTT

Noncanonical GA and GG 5' Intron Donor Splice Sites Are Common in the Copepod Eurytemora affinis

The noncanonical 5' intron donor splice sites GA and GG are exceedingly rare in described eukaryotic genomes; however, they are present in ~12% of introns in the genome of the copepod Eurytemora affinis. Failure to recognize the high frequency of these donor sites compromised the modeling of genes in this newly sequenced genome, including 10 conserved ionotropic glutamate receptor (GluR) family genes curated herein. These introns appear to have been acquired recently, along with many additional idiosyncratic introns. Their high frequency implies the evolution of modified intron donor splice site recognition in this copepod.



from Genetics via xlomafota13 on Inoreader http://ift.tt/2AUhlFu
via IFTTT

H+ and Pi Byproducts of Glycosylation Affect Ca2+ Homeostasis and Are Retrieved from the Golgi Complex by Homologs of TMEM165 and XPR1

Glycosylation reactions in the Golgi complex and the endoplasmic reticulum utilize nucleotide sugars as donors and produce inorganic phosphate (Pi) and acid (H+) as byproducts. Here we show that homologs of mammalian XPR1 and TMEM165 (termed Erd1 and Gdt1) recycle luminal Pi and exchange luminal H+ for cytoplasmic Ca2+, respectively, thereby promoting growth of yeast cells in low Pi and low Ca2+ environments. As expected for reversible H+/Ca2+ exchangers, Gdt1 also promoted growth in high Ca2+ environments when the Golgi-localized V-ATPase was operational but had the opposite effect when the V-ATPase was eliminated. Gdt1 activities were negatively regulated by calcineurin signaling and by Erd1, which recycled the Pi byproduct of glycosylation reactions and prevented the loss of this nutrient to the environment via exocytosis. Thus, Erd1 transports Pi in the opposite direction from XPR1 and other EXS family proteins and facilitates byproduct removal from the Golgi complex together with Gdt1.



from Genetics via xlomafota13 on Inoreader http://ift.tt/2A1RJGK
via IFTTT

Heterogeneous Patterns of Genetic Diversity and Differentiation in European and Siberian Chiffchaff (Phylloscopus collybita abietinus/P. tristis)

Identification of candidate genes for trait variation in diverging lineages and characterization of mechanistic underpinnings of genome differentiation are key steps toward understanding the processes underlying the formation of new species. Hybrid zones provide a valuable resource for such investigations, since they allow us to study how genomes evolve as species exchange genetic material and to associate particular genetic regions with phenotypic traits of interest. Here, we use whole-genome resequencing of both allopatric and hybridizing populations of the European (Phylloscopus collybita abietinus) and the Siberian chiffchaff (P. tristis)—two recently diverged species which differ in morphology, plumage, song, habitat, and migration—to quantify the regional variation in genome-wide genetic diversity and differentiation, and to identify candidate regions for trait variation. We find that the levels of diversity, differentiation, and divergence are highly heterogeneous, with significantly reduced global differentiation, and more pronounced differentiation peaks in sympatry than in allopatry. This pattern is consistent with regional differences in effective population size and recurrent background selection or selective sweeps reducing the genetic diversity in specific regions prior to lineage divergence, but the data also suggest that postdivergence selection has resulted in increased differentiation and fixed differences in specific regions. We find that hybridization and backcrossing is common in sympatry, and that phenotype is a poor predictor of the genomic composition of sympatric birds. The combination of a differentiation scan approach with identification of fixed differences pinpoint a handful of candidate regions that might be important for trait variation between the two species.



from Genetics via xlomafota13 on Inoreader http://ift.tt/2AUhdG0
via IFTTT

ARSDA: A New Approach for Storing, Transmitting and Analyzing Transcriptomic Data

Two major stumbling blocks exist in high-throughput sequencing (HTS) data analysis. The first is the sheer file size, typically in gigabytes when uncompressed, causing problems in storage, transmission, and analysis. However, these files do not need to be so large, and can be reduced without loss of information. Each HTS file, either in compressed .SRA or plain text .fastq format, contains numerous identical reads stored as separate entries. For example, among 44,603,541 forward reads in the SRR4011234.sra file (from a Bacillus subtilis transcriptomic study) deposited at NCBI's SRA database, one read has 497,027 identical copies. Instead of storing them as separate entries, one can and should store them as a single entry with the SeqID_NumCopy format (which I dub as FASTA+ format). The second is the proper allocation of reads that map equally well to paralogous genes. I illustrate in detail a new method for such allocation. I have developed ARSDA software that implement these new approaches. A number of HTS files for model species are in the process of being processed and deposited at http://ift.tt/2mcG65G to demonstrate that this approach not only saves a huge amount of storage space and transmission bandwidth, but also dramatically reduces time in downstream data analysis. Instead of matching the 497,027 identical reads separately against the B. subtilis genome, one only needs to match it once. ARSDA includes functions to take advantage of HTS data in the new sequence format for downstream data analysis such as gene expression characterization. I contrasted gene expression results between ARSDA and Cufflinks so readers can better appreciate the strength of ARSDA. ARSDA is freely available for Windows, Linux. and Macintosh computers at http://ift.tt/2mcMbPE.



from Genetics via xlomafota13 on Inoreader http://ift.tt/2A3zKj6
via IFTTT

Long-Term Impact of Optimum Contribution Selection Strategies on Local Livestock Breeds with Historical Introgression Using the Example of German Angler Cattle

The long-term performance of different selection strategies was evaluated via simulation using the example of a local cattle breed, German Angler cattle. Different optimum contribution selection (OCS) approaches to maximize genetic gain were compared to a reference scenario without selection and truncation selection. The kinships and migrant contribution (MC) were estimated from genomic data. Truncation selection achieved the highest genetic gain but decreased diversity considerably at native alleles. It also caused the highest increase in MCs. Traditional OCS, which only constrains kinship, achieved almost the same genetic gain but also caused a small increase of MC and remarkably reduced the diversity of native alleles. When MC was required not to increase and the increase of kinship at native alleles was restricted, the MC levels and the diversity at native alleles were well managed, and the genetic gain was only slightly reduced. However, genetic progress was substantially lower in the scenario that aimed to recover the original genetic background. Truncation selection and traditional OCS selection both reduce the genetic originality of breeds with historical introgression. The inclusion of MC and kinship at native alleles as additional constraints in OCS showed great potential for conservation. Recovery of the original genetic background is possible but requires many generations of selection and reduces the genetic progress in performance traits. Hence, constraining MCs at their current values can be recommended to avoid further reduction of genetic originality.



from Genetics via xlomafota13 on Inoreader http://ift.tt/2AUh4SY
via IFTTT

A Horizontally Transferred Autonomous Helitron Became a Full Polydnavirus Segment in Cotesia vestalis

Bracoviruses associate symbiotically with thousands of parasitoid wasp species in the family Braconidae, working as virulence gene vectors, and allowing the development of wasp larvae within hosts. These viruses are composed of multiple DNA circles that are packaged into infective particles, and injected together with wasp's eggs during parasitization. One of the viral segments of Cotesia vestalis bracovirus contains a gene that has been previously described as a helicase of unknown origin. Here, we demonstrate that this gene is a Rep/Helicase from an intact Helitron transposable element that covers the viral segment almost entirely. We also provide evidence that this element underwent at least two horizontal transfers, which appear to have occurred consecutively: first from a Drosophila host ancestor to the genome of the parasitoid wasp C. vestalis and its bracovirus, and then from C. vestalis to a lepidopteran host (Bombyx mori). Our results reinforce the idea of parasitoid wasps as frequent agents of horizontal transfers in eukaryotes. Additionally, this Helitron-bracovirus segment is the first example of a transposable element that effectively became a whole viral circle.



from Genetics via xlomafota13 on Inoreader http://ift.tt/2A1Rw6q
via IFTTT

Human intestinal spirochetosis mimicking ulcerative colitis

Abstract

Human intestinal spirochetosis (HIS) is a colorectal infection caused by the Brachyspira species of intestinal spirochetes, whose pathogenicity in humans remains unclear owing to the lack of or mild symptoms. We monitored the 5-year clinical course of a woman diagnosed with HIS in whom ulcerative colitis (UC) had been suspected. Following a positive fecal occult blood test, she underwent a colonoscopic examination at a local clinic where she was diagnosed with "right-sided" UC concomitant with incidentally detected HIS, and was referred to our hospital. Colonoscopic, histopathological, and cytological examination revealed localized erosive colitis in the ascending and the right transverse colon concomitant with HIS resembling skip lesions of UC. Initially, we chose the wait-and-watch approach; however, she gradually developed bloody diarrhea. Metronidazole improved her abdominal symptoms, as well as her colonoscopic and histopathological findings, suggesting that HIS was responsible for her colorectal inflammation. This case reveals (1) a possible pro-inflammatory role of HIS, (2) difficulties in diagnosing HIS in chronic proctocolitis, and (3) a possible inclusion of some HIS cases in "UC". HIS could mimic UC and might be included in differential diagnoses for UC. Antibiotic administration is necessary following the detection of HIS, particularly in patients demonstrating an atypical presentation of UC.



from Gastroenterology via xlomafota13 on Inoreader http://ift.tt/2noLYgp
via IFTTT

Development and Validation of a Japanese Fidelity Scale for Supported Employment

Abstract

The Individual Placement and Support (IPS) model of supported employment is an evidence based practice. Although several agencies have been trying to implement the IPS-model since 2005 in Japan, there was no tool to assess the quality. This study developed a Japanese version of the 25-item Individualized Supported Employment Fidelity Scale (J-ISEF), a new Japanese fidelity tool for supported employment based on the IPS model. A working group consisting of researchers and practitioners was formed to develop J-ISEF based on IPS-25. Some experts of the group visited the community agencies in Vermont before the development process. Twenty-six eligible agencies were identified using snowball sampling, and 14 agencies of them agreed and participated at T1. We conducted three cross-sectional surveys (T1, T2 and T3), using the new scale. The first evaluation period (T1) was between September 2013 and February 2014, the second (T2) between September 2014 and February 2015, and the third (T3) between October 2015 and February 2016. High inter-rater reliability (ICC = 0.98 for the entire scale) was confirmed from T1 data. The total score and the service subscale total were positively correlated with employment rate (P < 0.05). A new fidelity scale, J-ISEF, is developed as a quality assessment tool for evidence-based supported employment programs in Japan. The evidence for its inter-rater reliability and criterion-related validity is promising.



from Health via xlomafota13 on Inoreader http://ift.tt/2jdjB01
via IFTTT

Authorization of tissues from deceased patients for genetic research

Abstract

Tissues from deceased donors provide important data for genomic research and Organ Procurement Organizations (OPOs) play a significant role. To understand the decisions of families who donated for transplantation and made decisions about donation to the Genotype-Tissue Expression Project (GTEx), we examined donation decisions of family decision makers (FDMs). 413 families were interviewed by telephone. The OPO staff who made the transplant and research requests completed self-administered surveys; a total of 309 matching surveys from 99 OPO staff were obtained. 76.8% of families donated to the GTEx project. Logistic regression analysis found that FDM consent to GTEx donation was associated with endorsement of policies to promote biobanking (OR = 1.35), positive attitudes about medical research (OR = 1.1), lack of concern regarding a breach of confidentiality (OR = 1.54), comfort with tissue donation (OR = 1.24), and prior authorization to solid organ donation (OR = 3.17). OPO staff characteristics associated with GTEx donation included being female (OR = 3.57), White (OR = 4.97), comfort with hospital staff role in donation (OR = 1.61), and number of topics discussed with families (OR = 57.9). Donor type, FDM attitudes, OPO staff sociodemographics, OPO comfort with the GTEx authorization process, and intensity of discussing research-specific issues were significantly associated with GTEx donation decisions.



from Genetics via xlomafota13 on Inoreader http://ift.tt/2BvwOYO
via IFTTT

A targeted sequencing panel identifies rare damaging variants in multiple genes in the cranial neural tube defect, anencephaly

ABSTRACT

Neural tube defects (NTDs) affecting the brain (anencephaly) are lethal before or at birth, whereas lower spinal defects (spina bifida) may lead to life-long neurological handicap. Collectively NTDs rank among the most common birth defects worldwide. This study focuses on anencephaly, which despite having a similar frequency to spina bifida and being the most common type of NTD observed in mouse models, has had more limited inclusion in genetic studies. A genetic influence is strongly implicated in determining risk of NTDs and a molecular diagnosis is of fundamental importance to families both in terms of understanding the origin of the condition and for managing future pregnancies. Here we used a custom panel of 191 NTD candidate genes to screen 90 patients with cranial NTDs (n=85 anencephaly and n=5 craniorachischisis) with a targeted exome sequencing platform. After filtering and comparing to our in-house control exome database (N=509), we identified 397 rare variants (MAF<1%), 21 of which were previously unreported and predicted damaging. This included 1 frameshift (PDGFRA), 2 stop-gained (MAT1A; NOS2) and 18 missense variations. Together with evidence for oligogenic inheritance, this study provides new information on the possible genetic causation of anencephaly.

Thumbnail image of graphical abstract

from Genetics via xlomafota13 on Inoreader http://ift.tt/2iLP9gv
via IFTTT