Recent advances on the δ opioid receptor: from trafficking to function

Within the opioid family of receptors, δ (DOPrs) and μ opioid receptors (MOPrs) are typical GPCRs that activate canonical second-messenger signalling cascades to influence diverse cellular functions in neuronal and non-neuronal cell types. These receptors activate well-known pathways to influence ion channel function and pathways such as the map kinase cascade, AC and PI3K. In addition new information regarding opioid receptor-interacting proteins, downstream signalling pathways and resultant functional effects has recently come to light. In this review, we will examine these novel findings focusing on the DOPr and, in doing so, will contrast and compare DOPrs with MOPrs in terms of differences and similarities in function, signalling pathways, distribution and interactions. We will also discuss and clarify issues that have recently surfaced regarding the expression and function of DOPrs in different cell types and analgesia.

LINKED ARTICLES

This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2     

Hypertension in women: the Women Take Heart project

Hypertension is an important, modifiable risk for cardiovascular disease. The Women Take Heart study, a prospective, community-based cohort study of risk factors for heart disease, provides an opportunity to examine prevalence, awareness, and control of hypertension specifically in women. In 1992, 5932 women, age 35 and older (mean age, 52.9; 86% white, 9% African American, 5% other) and free of active heart disease symptoms for 3 months, were recruited through Chicago area public announcements, and their baseline examination data analyzed. Overall, 47.6% were hypertensive (systolic blood pressure 140 mm Hg or diastolic blood pressure 90 mm Hg, or self-report). Only 17.3% reported being hypertensive; in 63.2% of all hypertensive women, the hypertension was undetected or unacknowledged. Blood pressure was controlled to <140/90 mm Hg in 24.1% of self-reported hypertensives. Results from this study and national surveys indicate that hypertension detection and control remain major public health challenges in preventing cardiovascular disease in older women.     

Accuracy of computer-aided image analysis in the diagnosis of odontogenic cysts: A systematic review

Background This study aimed to search for scientific evidence concerning the accuracy of computer-assisted analysis for diagnosing odontogenic cysts. Material and Methods A systematic review was conducted according to the PRISMA statements and considering eleven databases, including the grey literature. Protocol was registered in PROSPERO (CRD 42020189349). The PECO strategy was used to define the eligibility criteria and only studies involving diagnostic accuracy were included. Their risk of bias was investigated using the Joanna Briggs Institute Critical Appraisal tool. Results Out of 437 identified citations, five papers, published between 2006 and 2019, fulfilled the criteria and were included in this systematic review. A total of 5,264 images from 508 lesions, classified as radicular cyst, odontogenic keratocyst, lateral periodontal cyst, glandular odontogenic cyst, or dentigerous cyst, were analyzed. All selected articles scored low risk of bias. In three studies, the best performances were achieved when the two subtypes of odontogenic keratocysts (solitary or syndromic) were pooled together, the case-wise analysis showing a success rate of 100% for odontogenic keratocysts and radicular cysts, in one of them. In two studies, the dentigerous cyst was associated with the majority of misclassifications, and its omission from the dataset improved significantly the classification rates. Conclusions The overall evaluation showed all studies presented high accuracy rates of computer-aided systems in classifying odontogenic cysts in digital images of histological tissue sections. However, due to the heterogeneity of the studies, a meta-analysis evaluating the outcomes of interest was not performed and a pragmatic recommendation about their use is not possible. Key words:Computer-assisted diagnosis, computer-assisted image analysis, computer-assisted image processing, odontogenic cysts, keratocysts, radicular cysts.     

Influence of muscle strength to weight ratio on functional task performance

Existing models of muscle deconditioning such as bed rest are expensive and time-consuming. We propose a new model utilizing a weighted suit to manipulate muscle strength, power, or endurance relative to body weight. The aims of the study were to determine as to which muscle measures best predict functional task performance and to determine muscle performance thresholds below which task performance is impaired. Twenty subjects performed seven occupational astronaut tasks (supine and upright seat egress and walk, rise from fall, hatch opening, ladder climb, object carry, and construction board activity), while wearing a suit weighted with 0–120 % of body weight. Models of the relationship between muscle function/body weight and task completion time were developed using fractional polynomial regression and verified with pre- and post-flight astronaut performance data. Spline regression was used to identify muscle function thresholds for each task. Upright seat egress and walk was the most difficult task according to the spline regression analysis thresholds. Thresholds normalized to body weight were 17.8 N/kg for leg press isometric force, 17.6 W/kg for leg press power, 78.8 J/kg for leg press work, 5.9 N/kg isometric knee extension and 1.9 Nm/kg isokinetic knee extension torque. Leg press maximal isometric force/body weight was the most reliable measure for modeling performance of ambulatory tasks. Laboratory-based manipulation of relative strength has promise as an analog for spaceflight-induced loss of muscle function. Muscle performance values normalized to body weight can be used to predict occupational task performance and to establish relevant strength thresholds.     

Concurrent partnerships in Cape Town,South Africa: race and sex differences in prevalence and duration of overlap

Introduction

Concurrent partnerships (CPs) have been suggested as a risk factor for transmitting HIV, but their impact on the epidemic depends upon how prevalent they are in populations, the average number of CPs an individual has and the length of time they overlap. However, estimates of prevalence of CPs in Southern Africa vary widely, and the duration of overlap in these relationships is poorly documented. We aim to characterize concurrency in a more accurate and complete manner, using data from three disadvantaged communities of Cape Town, South Africa.

Methods

We conducted a sexual behaviour survey (n=878) from June 2011 to February 2012 in Cape Town, using Audio Computer-Assisted Self-Interviewing to collect sexual relationship histories on partners in the past year. Using the beginning and end dates for the partnerships, we calculated the point prevalence, the cumulative prevalence and the incidence rate of CPs, as well as the duration of overlap for relationships begun in the previous year. Linear and binomial regression models were used to quantify race (black vs. coloured) and sex differences in the duration of overlap and relative risk of having CPs in the past year.

Results

The overall point prevalence of CPs six months before the survey was 8.4%: 13.4% for black men, 1.9% for coloured men, 7.8% black women and 5.6% for coloured women. The median duration of overlap in CPs was 7.5 weeks. Women had less risk of CPs in the previous year than men (RR 0.43; 95% CI: 0.32–0.57) and black participants were more at risk than coloured participants (RR 1.86; 95% CI: 1.17–2.97).

Conclusions

Our results indicate that in this population the prevalence of CPs is relatively high and is characterized by overlaps of long duration, implying there may be opportunities for HIV to be transmitted to concurrent partners.     

Naturalistic outcomes for a day‐hospital programme in a mixed diagnostic sample of adolescents with eating disorders

Despite initial data suggesting positive treatment outcomes for adolescent eating disorder day‐hospital programmes (DHPs), existing studies have included limited follow‐up, small samples, and a focus on restricting‐type eating disorders. To address these gaps, we explored naturalistic outcomes for an adolescent eating disorders DHP. Adolescent participants (N = 265) completed measurements at treatment admission, discharge (n = 170), and various lengths of follow‐up (n = 126; M_{follow up} = 278.87 days). Results from multilevel models indicated significant increases in body weight for the anorexia nervosa group throughout treatment and maintenance of increased body weight from discharge to follow‐up. In bulimic spectrum disorders, binge eating and purging significantly decreased from intake to discharge and did not change from discharge to follow‐up. Across the entire sample, eating disorder symptoms decreased from intake to discharge and did not change from discharge to follow‐up. Further, anxiety and depression decreased over the course of treatment and continued to decrease over the follow‐up period. The current investigation represents the first study to explore longitudinal DHP outcomes within adolescent bulimic spectrum eating disorders. Our findings also highlight many challenges inherent in conducting naturalistic research; it is critical that the field continue to develop solutions to the barriers inherent in conducting longitudinal research on eating disorder treatment.     

Aggregation-prone c9FTD/ALS poly(GA) RAN-translated proteins cause neurotoxicity by inducing ER stress

The occurrence of repeat-associated non-ATG (RAN) translation, an atypical form of translation of expanded repeats that results in the synthesis of homopolymeric expansion proteins, is becoming more widely appreciated among microsatellite expansion disorders. Such disorders include amyotrophic lateral sclerosis and frontotemporal dementia caused by a hexanucleotide repeat expansion in the C9ORF72 gene (c9FTD/ALS). We and others have recently shown that this bidirectionally transcribed repeat is RAN translated, and the “c9RAN proteins” thusly produced form neuronal inclusions throughout the central nervous system of c9FTD/ALS patients. Nonetheless, the potential contribution of c9RAN proteins to disease pathogenesis remains poorly understood. In the present study, we demonstrate that poly(GA) c9RAN proteins are neurotoxic and may be implicated in the neurodegenerative processes of c9FTD/ALS. Specifically, we show that expression of poly(GA) proteins in cultured cells and primary neurons leads to the formation of soluble and insoluble high molecular weight species, as well as inclusions composed of filaments similar to those observed in c9FTD/ALS brain tissues. The expression of poly(GA) proteins is accompanied by caspase-3 activation, impaired neurite outgrowth, inhibition of proteasome activity, and evidence of endoplasmic reticulum (ER) stress. Of importance, ER stress inhibitors, salubrinal and TUDCA, provide protection against poly(GA)-induced toxicity. Taken together, our data provide compelling evidence towards establishing RAN translation as a pathogenic mechanism of c9FTD/ALS, and suggest that targeting the ER using small molecules may be a promising therapeutic approach for these devastating diseases.