Sample preparation for high-throughput sequencing (HTS) includes treatment with various laboratory components, potentially carrying viral nucleic acids, the extent of which has not been thoroughly ...investigated. Our aim was to systematically examine a diverse repertoire of laboratory components used to prepare samples for HTS in order to identify contaminating viral sequences.
A total of 322 samples of mainly human origin were analysed using eight protocols, applying a wide variety of laboratory components. Several samples (60% of human specimens) were processed using different protocols. In total, 712 sequencing libraries were investigated for viral sequence contamination.
Among sequences showing similarity to viruses, 493 were significantly associated with the use of laboratory components. Each of these viral sequences had sporadic appearance, only being identified in a subset of the samples treated with the linked laboratory component, and some were not identified in the non-template control samples. Remarkably, more than 65% of all viral sequences identified were within viral clusters linked to the use of laboratory components.
We show that high prevalence of contaminating viral sequences can be expected in HTS-based virome data and provide an extensive list of novel contaminating viral sequences that can be used for evaluation of viral findings in future virome and metagenome studies. Moreover, we show that detection can be problematic due to stochastic appearance and limited non-template controls. Although the exact origin of these viral sequences requires further research, our results support laboratory-component-linked viral sequence contamination of both biological and synthetic origin.
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Aliment Pharmacol Ther 2012; 35: 154–164
Summary
Background The evolution of gastro‐oesophageal reflux disease (GERD) under current management options remains uncertain.
Aim To examine whether, ...depending on the initial presentation, non‐erosive (NERD) and erosive reflux disease (ERD) without Barrett’s oesophagus will progress to more severe disease under current routine care following the resolution of the initial condition.
Methods Patients with the primary symptom of heartburn were included at baseline, and stratified into non‐erosive (NERD) and erosive reflux disease (ERD), LA grades A–D (Los Angeles classification). After a 2‐ to 8‐week course with esomeprazole therapy to achieve endoscopic healing in ERD and symptom relief in NERD, patients were treated routinely at the discretion of their physician. We report oesophagitis status and the presence of endoscopic and confirmed Barrett’s oesophagus after 5 years.
Results A total of 6215 patients were enrolled in the study of whom 2721 patients completed the 5‐year follow‐up. Progression, regression and stability of GERD severity were followed from baseline to 5 years. Only a few patients with NERD and mild/moderate ERD progressed to severe forms of ERD and even Barrett’s oesophagus. Most patients remained stable or showed improvement in their oesophagitis; 5.9% of the NERD patients, 12.1% of LA grade A/B patients and 19.7% of LA grade C/D patients in whom no Barrett’s oesophagus was recorded at baseline progressed to endoscopic or confirmed Barrett’s oesophagus at 5 years.
Conclusion Most GERD patients remain stable or improve over a 5‐year observation period under current routine clinical care.
A functional serotonin transporter promoter polymorphism, HTTLPR, alters the risk of disease as well as brain morphometry and function. Here, we show that HTTLPR is functionally triallelic. The LG ...allele, which is the L allele with a common G substitution, creates a functional AP2 transcription-factor binding site. Expression assays in 62 lymphoblastoid cell lines representing the six genotypes and in transfected raphe-derived cells showed codominant allele action and low, nearly equivalent expression for the S and LG alleles, accounting for more variation in HTT expression than previously recognized. The gain-of-function LALA genotype was approximately twice as common in 169 whites with obsessive-compulsive disorder (OCD) than in 253 ethnically matched controls. We performed a replication study in 175 trios consisting of probands with OCD and their parents. The LA allele was twofold overtransmitted to the patients with OCD. The HTTLPR LALA genotype exerts a moderate (1.8-fold) effect on risk of OCD, which crystallizes the evidence that the HTT gene has a role in OCD.
The role of the right hemisphere for language processing and successful therapeutic interventions in aphasic patients is a matter of debate. This study explored brain activation in right-hemispheric ...areas and left-hemispheric perilesional areas in response to language tasks in chronic non-fluent aphasic patients before and after constraint-induced aphasia therapy (CIAT). In particular, we analysed the relation between brain responses and therapy outcome. Using functional magnetic resonance imaging (fMRI), brain activation was measured during word-reading (REA) and word-stem completion (COM) in 16 chronic non-fluent aphasic and 8 healthy subjects. Before therapy, activation in right inferior frontal gyrus/insula (IFG/IC) was stronger in aphasics compared to controls during REA and in precentral gyrus (PCG) during COM. Therapeutic intervention per se did not change brain activation for either task across all aphasic subjects. However, therapeutic success correlated with a relative decrease of activation in right-hemispheric areas, including the IFG/IC. Most importantly, initial activation in right IFG/IC and other right-hemispheric areas correlated positively with subsequent therapy success. Thus, right-hemispheric activation prior to aphasia therapy strongly predicts therapeutic success, suggesting that brain activation in chronic aphasia indicates the patients’ potential for further language improvement.
The 2018 ISDE achalasia guidelines Zaninotto, G; Bennett, C; Boeckxstaens, G ...
Diseases of the esophagus,
2018-Sep-01, 2018-09-01, 20180901, Volume:
31, Issue:
9
Journal Article
Peer reviewed
Open access
Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, ...patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.
Both undiagnosed celiac disease and some chronic childhood diseases are associated with lower academic achievement. However, there is little knowledge of achievements in those diagnosed with celiac ...disease. Our aim was to investigate school achievements in upper secondary school among Swedish adolescents with celiac disease.
We performed a retrospective cohort study using register data. We analyzed choice of upper secondary school program, completion of upper secondary school including achievements of basic eligibility for college/university, and final grade in individuals with celiac disease diagnosed before 15 years of age, born 1991-97. We compared with the Swedish population of the same birth years. Analyses were adjusted for sex, year of birth, living region at 17 years of age, and parental education as well as income.
The cohort included 734 074 individuals, whereof 3 257 (62% females) with celiac disease. There was no significant difference in choice of upper secondary school program. No significant difference was found in completion or achieving basic eligibility for college/university in adjusted analyses. The mean final grade in the celiac disease group was 13.34 (standard deviation 4.85) compared to 12.78 (standard deviation 5.01) in the reference population (p < 0.001), out of a maximum of 20. The effect of celiac disease on final grade remained in adjusted analyses (p = 0.012).
We found that diagnosed celiac disease does not negatively affect school achievements in upper secondary school. This finding suggests the diagnosis, treatment and follow-up programs of celiac disease could reverse potential deleterious academic processes.
Easily processed materials with the ability to transport excitons over length scales of more than 100 nanometers are highly desirable for a range of light-harvesting and optoelectronic devices. We ...describe the preparation of organic semiconducting nanofibers comprising a crystalline poly(di-
-hexylfluorene) core and a solvated, segmented corona consisting of polyethylene glycol in the center and polythiophene at the ends. These nanofibers exhibit exciton transfer from the core to the lower-energy polythiophene coronas in the end blocks, which occurs in the direction of the interchain π-π stacking with very long diffusion lengths (>200 nanometers) and a large diffusion coefficient (0.5 square centimeters per second). This is made possible by the uniform exciton energetic landscape created by the well-ordered, crystalline nanofiber core.
•Extract from Terminalia actinophylla (TAE) is not genotoxic in SMART.•Neither MMC nor EMS genotoxicity was modified by the post-exposure to TAE.•Co-treatment with TAE lead to a significant ...protection against the genotoxicity of MMC.•Modulation by TAE could be related to its antioxidative potential.
Terminalia actinophylla has been used for anti-diarrheic and haemostatic purposes in Brazil. The fly spot data obtained after exposure of marker-heterozygous Drosophila melanogaster larvae to T. actinophylla ethanolic extract (TAE) in the standard (ST) and high bioactivation (HB) crosses revealed that TAE did not induce any statistically significant increment in any spot categories. Differences between the two crosses are related to cytochrome P450 (CYPs) levels. In this sense, our data pointed out the absence of TAE-direct and indirect mutagenic and recombinagenic action in the Somatic Mutation and Recombination Test (SMART). When the anti-genotoxicity of TAE was analyzed, neither mitomycin C (MMC) nor ethylmethanesulfonate (EMS) genotoxicity was modified by the post-exposure to TAE, which suggests that TAE has no effect on the mechanisms involved in the processing of the lesions induced by both genotoxins. In the mwh/flr3 genotype, co-treatment with TAE may lead to a significant protection against the genotoxicity of MMC and a weak but significant effect in the toxic genetic action of EMS. The overall findings suggested that the favorable modulations by TAE could be, at least in part, due to its antioxidative potential.
Gender dysphoria (GD) is often accompanied by dissatisfaction with physical appearance and body image problems. The aim of this study was to compare body satisfaction with perceived appearance by ...others in various GD subgroups. Data collection was part of the European Network for the Investigation of Gender Incongruence. Between 2007 and 2012, 660 adults who fulfilled the criteria of the DSM-IV gender identity disorder diagnosis (1.31:1 male-to-female MtF:female-to-male FtM ratio) were included into the study. Data were collected before the start of clinical gender-confirming interventions. Sexual orientation was measured via a semi-structured interview whereas onset age was based on clinician report. Body satisfaction was assessed using the Body Image Scale. Congruence of appearance with the experienced gender was measured by means of a clinician rating. Overall, FtMs had a more positive body image than MtFs. Besides genital dissatisfaction, problem areas for MtFs included posture, face, and hair, whereas FtMs were mainly dissatisfied with hip and chest regions. Clinicians evaluated the physical appearance to be more congruent with the experienced gender in FtMs than in MtFs. Within the MtF group, those with early onset GD and an androphilic sexual orientation had appearances more in line with their gender identity. In conclusion, body image problems in GD go beyond sex characteristics only. An incongruent physical appearance may result in more difficult psychological adaptation and in more exposure to discrimination and stigmatization.
•Cigarette whole smoke solutions (WSSs) were tested for micronucleus induction.•Assays were conducted in L5178YTk+/− and TK6 cells.•Data were analyzed by BMD potency ranking.•BMDs differed by ...cigarette type, number smoked, and smoking protocol used to make the WSS.
Dose-response modeling of in vitro micronucleus test (IVMNT) data was evaluated to determine if the approach has value in discriminating among different tobacco products. Micronucleus responses were generated in L5178Y/Tk+/− mouse lymphoma cells and TK6 human lymphoblastoid cells from a series of whole smoke solutions (WSSs) expected to have different levels of genotoxicity based on differences in their machine-generated smoke constituents. Eight WSSs were prepared by machine smoking different numbers (20 or 60) of two commercial cigarettes (Marlboro Silver or Red) under International Standardization Organization (ISO) or Health Canada Intense (HCI) smoking machine regimens and tested in the two cell lines with and without rat liver S9 activation. The S9-mediated IVMNT dose-response data from the WSSs were evaluated with PROAST software and Benchmark Doses (BMDs) and their upper and lower confidence intervals (CIs) were generated. IVMNT data differed based on the number and type of cigarettes smoked and smoking machine regimen. The IVMNT responses produced in mouse lymphoma cells generally were greater than in TK6 cells, but the ability of the two cell types to differentiate between WSSs was similar. The results indicate that BMD potency ranking was useful for differentiating between IVMNT responses.
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