A rare missense variant in RCL1 segregates with depression in extended families.

Depression is the most prevalent psychiatric disorder with a complex and elusive etiology that is moderately heritable. Identification of genes would greatly facilitate the elucidation of the biological mechanisms underlying depression, however, its complex etiology has proved to be a major bottleneck in the identification of its genetic risk factors, especially in genome-wide association-like studies. In this study, we exploit the properties of a genetic isolate and its family-based structure to explore whether relatively rare exonic variants influence the burden of depressive symptoms in families. Using a multistep approach involving linkage and haplotype analyses followed by exome sequencing in the Erasmus Rucphen Family (ERF) study, we identified a rare (minor allele frequency (MAF)=1%) missense c.1114C>T mutation (rs115482041) in the RCL1 gene segregating with depression across multiple generations. Rs115482041 showed significant association with depressive symptoms (N=2393, ßT-allele=2.33, P-value=1 × 10-4) and explained 2.9% of the estimated genetic variance of depressive symptoms (22%) in ERF. Despite being twice as rare (MAF<0.5%), c.1114C>T showed similar effect and significant association with depressive symptoms in samples from the independent population-based Rotterdam study (N=1604, ßT-allele=3.60, P-value=3 × 10-2). A comparison of RCL1 expression in human and mouse brain revealed a striking co-localization of RCL1 with the layer 1 interlaminar subclass of astrocytes found exclusively in higher-order primates. Our findings identify RCL1 as a novel candidate gene for depression and offer insights into mechanisms through which RCL1 may be relevant for depression.

The new grasper-integrated single use flexible cystoscope for double J stent removal: evaluation of image quality, flow and flexibility.

BACKGROUND: A new single use digital flexible cystoscope (FC) Isiris α from Coloplast® with an incorporated grasper has been developed to perform double J stent removal. There is a lack of data regarding the comparison of image quality, flexibility and flow between classic cystoscopes and the new Isiris α. MATERIALS AND METHODS: Five different FC were used to compare the image quality, the field of view, the loss of flow and the deflection loss. Two standardized grids, three stones of different composition and a ruler's image were filmed in four standardized different scenarios. These videos were shown to thirty subjects that had to evaluate them. Water outflow was measured in ml/sec in all devices with and without the grasper inside, instruments tip deflection was measured using a software. RESULTS: In the subjective analysis of the image quality Isiris α was the second FC best scored. At 3 cm of distance, the field view of Isiris α was the narrowest. Comparing the water flow in the different FCs, we observed a water flow decrease in all cystoscopes when the grasper was loaded in the working channel. Isiris α deflection and flow increase when the grasper is activated. CONCLUSION: In terms of quality of vision and water flow, the FC Isiris α is comparable to the other digital FC tested. Field of view is narrower. The results displayed a valid alternative to the standard procedure for DJ removal.

Self-management in temporomandibular disorders: a systematic review of behavioural components.

The aim of this qualitative systematic review was to identify the behaviour change techniques most frequently employed in published temporomandibular disorder (TMD) self-management (SM) programmes. The reviewers matched the components of SM programmes into the relevant behaviour change technique domains according to the definitions of the behaviour change taxonomy (version 1). Electronic databases were searched for randomised controlled trials assessing an SM programme for TMD. Manual searches were also conducted for potentially important journals. Eligibility criteria for the review included: the type of study, the participants, the intervention utilised and the comparators/control. Fifteen randomised controlled trials with 554 patients were included in this review. The review concludes a minority of the available behaviour change techniques are currently employed in SM programmes. Other behaviour change techniques should be examined to see whether there is a theoretical underpinning that might support their inclusion in self-management programmes in TMD. Further trials are required to conclude that SM programmes are more effective than no treatment at all and or placebo. With more structured SM programmes, greater therapeutic benefits might be achieved, and certainly if SM programmes published in the literature define their components through use of the behaviour change taxonomy, it would be easier for clinicians to replicate efficacious programmes.

Self-management programmes in temporomandibular disorders: results from an international Delphi process.

Self-management (SM) programmes are commonly used for initial treatment of patients with temporomandibular disorders (TMD). The programmes described in the literature, however, vary widely with no consistency in terminology used, components of care or their definitions. The aims of this study were therefore to construct an operationalised definition of self-management appropriate for the treatment of patients with TMD, identify the components of that self-management currently being used and create sufficiently clear and non-overlapping standardised definitions for each of those components. A four-round Delphi process with eleven international experts in the field of TMD was conducted to achieve these aims. In the first round, the participants agreed upon six principal concepts of self-management. In the remaining three rounds, consensus was achieved upon the definition and the six components of self-management. The main components identified and agreed upon by the participants to constitute the core of a SM programme for TMD were as follows: education; jaw exercises; massage; thermal therapy; dietary advice and nutrition; and parafunctional behaviour identification, monitoring and avoidance. This Delphi process has established the principal concepts of self-management, and a standardised definition has been agreed with the following components for use in clinical practice: education; self-exercise; self-massage; thermal therapy; dietary advice and nutrition; and parafunctional behaviour identification, monitoring and avoidance. The consensus-derived concepts, definitions and components of SM offer a starting point for further research to advance the evidence base for, and clinical utility of, TMD SM.

Timing interventions in relation to temporomandibular joint closed lock duration: a systematic review of 'locking duration'.

Temporomandibular joint (TMJ) 'closed lock' (CL) is a clinical condition causing TMJ pain and limited mouth opening (painful locking) that is mostly attributed to disc displacement without reduction (DDwoR), or less commonly to anchored disc phenomenon (ADP). Both conditions are described clinically as CL that can be 'acute' or 'chronic' depending on the duration of locking. There is, however, no consensus about the duration of locking that defines the acute state and its effect on the success of interventions. This review paper, therefore, aims to provide: (i) a narrative review of the pathophysiological need for early intervention in DDwoR and the clinical implications of acute/chronic CL stages on the management pathway; (ii) a systematic review investigating the effects of locking duration on the success of interventions for CL management. Electronic and manual searches until mid-August 2013 were conducted for English-language studies of any design investigating the effects of non-surgical and surgical interventions for acute or chronic CL (DDwoR or ADP). A total of 626 records were identified, and 113 studies were included. Data extraction and quality assessment were completed for all included studies. Included studies were, however, heterogeneous and mostly of poor-quality leading to contradictory and inconsistent evidence on the effect of the duration of locking on treatment outcomes. Future high-quality trials investigating the effect of CL duration on treatment outcome are needed. At present, early intervention by 'unlock' mandibular manipulation seems to be the most practical and realistic approach that can be attempted first in every CL patient as an initial diagnostic/therapeutic approach.

Intramural esophageal dissection due to pharyngeal abscess treated by endoscopic esophageal transection: a case report.

Intramural esophageal dissection is a rare disorder characterized by extensive laceration between the mucosal and submucosal layers of the esophageal wall, but without perforation. The etiology of intramural dissection of the esophagus remains uncertain. Conservative management is usually considered adequate. Only one case of circumferential intramural esophageal dissection has been reported previously. We report here on a case due to an infectious cause (paryngeal abscess) that is also an unusual example of circumferential intramural esophageal dissection, which was then treated by endoscopic transection of the true internal esophageal wall and bougienage dilation.

Detoxification of Heterocyclic Aromatic Amines by Probiotic to Inhibit Medical Hazards.

Cancer is the second leading factor of human death in the world. Long-term consumption of cooked red meat brings about various types of cancers like colorectal cancer due to the formation of Heterocyclic Aromatic Amines (HAAs) during the heating process of meat. There are various solutions for the reduction of these toxicants. The aim of this article is to describe probiotic as one of the possible strategies for bioremoval of these carcinogenic and mutagenic substances and change food to functional one as well. The mechanism of biodetoxification is binding by probiotics, which depends on some variables including the probiotic characteristics, kind and content of the mutagens, as well as some properties of media. In this article, after introducing detoxification ability of probiotics and listing of all reported probiotics in this field, the influencing variables are surveyed and finally, opportunities and problems of HAA bioremoval by probiotics are described.

Decision-making in the management of TMJ disc displacement without reduction: A qualitative study.

OBJECTIVE: Patients with disc displacement without reduction (DDwoR) may suffer sudden-onset painful/limited mouth opening and immediately seek care from clinicians at the frontline. Currently, there is a lack of understanding of frontline, and specialist, clinicians' decision-making processes when encounter DDwoR patients. Understanding these processes and what influences them is an essential first-step towards the development of an evidence-informed behavioural intervention to improve first-line care of DDwoR patients. The objective of this study was to examine clinicians' decision-making processes in managing DDwoR and influences upon them. METHODS: A qualitative study informed by the Theoretical behaviour change Domains Framework (TDF) was conducted. The TDF-based topic guide was utilised in semi-structured interviews with a purposive sample of medical and dental frontline and specialist clinicians who might encounter patients with DDwoR. Interviews continued until data saturation across the theoretical domains was achieved (n = 21) and were analysed using the TDF to structure coding alongside framework analysis. RESULTS: The results highlighted the complexity of decision-making process and demonstrated the influences of all the domains on clinicians' decisions. Of the influential factors identified, the frontline clinicians placed most emphasis on their lack of: 'knowledge', 'skills', and 'experience' with DDwoR management. CONCLUSION: The clinicians at the frontline showed high degree of diagnostic and management uncertainty and preferred to refer DDwoR patients early. The frontline clinicians displayed lack of knowledge, experience, and training to diagnose and treat DDwoR. There is a need to enhance the clinicians' knowledge and skills in managing DDwoR at the first-point of contact. CLINICAL SIGNIFICANCE: The frontline clinicians showed unfamiliarity with DDwoR presentation and inability to diagnose and, consequently, treat DDwoR. This indicates that DDwoR patients may, currently, receive sub-optimal first-line care in the UK. Designing a behaviour change intervention informed by the identified theoretical domains can support the clinicians' decisions and improve patients' care.

Predictors of early, intermediate and late biochemical recurrence after minimally invasive radical prostatectomy in a single-centre cohort with a mean follow-up of 8 years. / Factores predictivos de recidiva bioquímica temprana, intermedia y tardía tras prostatectomía radical mínimamente invasiva en una cohorte unicéntrica con seguimiento medio de 8 años.

OBJECTIVE: To determine the predictors of early, intermediate and late biochemical recurrence (BR) following minimally invasive radical prostatectomy in patients with localised prostate cancer (PC). MATERIAL AND METHODS: We included 6195 patients with cT1-3N0M0 prostate cancer treated using radical laparoscopic prostatectomy (RLP) and radical robot-assisted prostatectomy at our institution between 2000 and 2016. None of the patients underwent adjuvant therapy. BR is defined as PSA levels ≥0.2 ng/dL. The time to BR is divided into terciles to identify the variables associated with early (<12 months), intermediate (12-36 months) and late (>36 months) recurrence. We employed logistic regression models to determine the risk factors associated with each interval. RESULTS: We identified 1148 (18.3%) patients with BR. The median time to BR was 24 months (IQR, 0.98-53.18). The multivariate analysis showed that preoperative PSA levels, lymph node invasion, positive margins and RLP are associated with early recurrence (P≤.029 for all). Laparoscopic surgery was the only predictor of intermediate recurrence (P=.001). The predictors of late recurrence included a pathological Gleason score ≥7, stage ≥pT3, positive margins and RLP (P≤.02 for all). CONCLUSIONS: The patients with high-risk prostate cancer can develop late recurrence and require long-term follow-up. Identifying patients with higher PSA levels and lymph node invasion has an important predictive role in the first year after surgery. The association between RLP and BR warrants further assessment.

Higher number of transrectal ultrasound guided prostate biopsy cores is associated with higher blood loss and perioperative complications in robot assisted radical prostatectomy. / Un mayor número de cilindros de biopsia transrectal de próstata guiada por ultrasonido se asocia con una mayor pérdida de sangre y complicaciones perioperatorias en la prostatectomía radical asistida por robot.

INTRODUCTION: The local inflammatory process after prostate biopsies can have a negative impact on functional outcomes of radical prostatectomy. There is no evidence in literature demonstrating its impact on radical prostatectomy. OBJECTIVES: To evaluate the impact of the number of TRUS core biopsies in the surgical morbidity and rate of positive margin on robot assisted radical prostatectomy (RARP). MATERIAL AND METHODS: A prospectively maintained database of 2,054 RARPs in a single institution. Patients were further grouped into 2 groups based on the number of TRUS biopsy cores (G1≤12 cores; G2>12 cores). Multivariable logistic regression model was applied to analyze the impact of number of cores on complications. RESULTS: A total number of 1,042 patients in the group 1 (≤12 cores) and 1,012 patients in the group 2 (>12 cores) were included. The rate of perioperative complications increased with higher number of biopsies (G1 6.4 vs. G2 8.5%; P=.03), but high grade complication (Clavien 3-4) were similar (G1 1.4 vs. G2 2.2%; P=.16). Positive surgical margin rates were similar in both groups (G1 11.8 vs. 9.98%; P=.2). At the multivariable logistic regression analysis shown that G2 had a 39% (OR 0.645) higher rate to experience perioperative complications during RARP. CONCLUSION: Higher number of TRUS biopsy cores (>12) is associated to higher blood loss and perioperative complications during RARP. Careful preoperative evaluation for those patients underwent multiple biopsies or saturation protocols is mandatory. Application of longer intervals (>6 weeks) between biopsy and surgery may be advisable to minimize potential risks of surgical complications in patients may benefit from RARP. Further studies are still necessary to confirm these results.

TMJ Disc Displacement without Reduction Management: A Systematic Review.

Various interventions have been used for the management of patients with temporomandibular joint (TMJ) disc displacement without reduction (DDwoR), but their clinical effectiveness remains unclear. This systematic review investigated the effects of these interventions and is reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic and manual searches up to November 1, 2013, were conducted for English-language, peer-reviewed, publications of randomized clinical trials comparing any form of conservative or surgical interventions for patients with clinical and/or radiologic diagnosis of acute or chronic DDwoR. Two primary outcomes (TMJ pain intensity and maximum mouth opening) and a number of secondary outcomes were examined. Two reviewers performed data extraction and risk of bias assessment. Data collection and analysis were performed according to Cochrane recommendations. Twenty studies involving 1,305 patients were included. Data analysis involved 21 comparisons between a variety of interventions, either between interventions, or between intervention and placebo or no intervention. Meta-analysis on homogenous groups was conducted in 4 comparisons. In most comparisons made, there were no statistically significant differences between interventions relative to primary outcomes at short- or long-term follow-up (p > .05). In a separate analysis, however, the majority of reviewed interventions reported significantly improved primary outcome measures from their baseline levels over time (p < .05). Evidence levels, however, are currently insufficient for definitive conclusions, because the included studies were too heterogeneous and at an unclear to high risk of bias. In view of the comparable therapeutic effects, paucity of high-quality evidence, and the greater risks and costs associated with more complex interventions, patients with symptomatic DDwoR should be initially treated by the simplest and least invasive intervention.