Tight control of translation is fundamental for eukaryotic cells, and deregulation of proteins implicated contributes to numerous human diseases. The neurodegenerative disorder spinocerebellar ataxia type 2 is caused by a trinucleotide expansion in the SCA2 gene encoding a lengthened polyglutamine stretch in the gene product ataxin-2, which seems to be implicated in cellular RNA-processing pathways and translational regulation. Here, we substantiate a function of ataxin-2 in such pathways by demonstrating that ataxin-2 interacts with the DEAD/H-box RNA helicase DDX6, a component of P-bodies and stress granules, representing cellular structures of mRNA triage. We discovered that altered ataxin-2 levels interfere with the assembly of stress granules and cellular P-body structures. Moreover, ataxin-2 regulates the intracellular concentration of its interaction partner, the poly(A)-binding protein, another stress granule component and a key factor for translational control. Thus, our data imply that the cellular ataxin-2 concentration is important for the assembly of stress granules and P-bodies, which are main compartments for regulating and controlling mRNA degradation, stability, and translation. INTRODUCTIONAn essential step in the control of global gene expression in eukaryotes is the regulation of mRNA translation and degradation. Shortening of the poly(A) tail is the initial step to trigger mRNA for decay in two major mRNA degradation pathways in eukaryotic cells (Bernstein and Ross, 1989;Peltz et al., 1991;Decker and Parker, 1994;Beelman and Parker, 1995). In one pathway, the deadenylated mRNA is degraded by a cytoplasmic protein complex, the exosome, consisting of a number of exonucleases with 3Ј-5Ј activity (Butler, 2002). In the other pathway, shortening of the poly(A) tail leads to the removal of the cap structure of the mRNA by the decapping proteins DCP1 and DCP2 facilitating 5Ј-3Ј degradation of the mRNA through the exoribonuclease XRN1 (Beelman and Parker, 1995;Butler, 2002). These proteins colocalize in discrete cytoplasmic foci in mammalian cells, termed processing bodies or P-bodies (also known as DCP1-or GW182-bodies), indicating that mRNA decay is restricted to distinct cytoplasmic compartments in mammalian cells (van Dijk et al., 2002;Cougot et al., 2004). The human protein CCR4, which is involved in mRNA deadenylation, the decapping stimulating LSm proteins LSm1-7, the DEAD/Hbox RNA helicase DDX6 (also known as RCK/p54), GW182, and Ge-1 are components of P-bodies (Bouveret et al., 2000;Eystathioy et al., 2002;Ingelfinger et al., 2002; LykkeAndersen, 2002;Cougot et al., 2004;Yu et al., 2005). Moreover, the RNA-associated protein 55, hEDC3, Hedls as well as factors of the RISC complex localize to P-bodies in mammalian cells (Fenger-Gron et al., 2005;Liu et al., 2005;Sen and Blau, 2005;Yang et al., 2006). P-bodies represent dynamic structures that are in an equilibrium with polysomes and contain nontranslating mRNA . Remarkably, recent work demonstrated that mRNA molecules entering P-bodies can a...

BackgroundHigh utilization of health care services is a costly phenomenon commonly observed in primary care practices. However, while frequent attendance in primary care has been broadly studied across age groups, aspects of high utilization by elderly patients have not been investigated in detail. The aim of this paper is to provide a systematic review of frequent attendance in primary care among elderly people.MethodsWe searched five databases (PubMed, PsycINFO, Web of Science, PubPsych, and Cochrane Library) for published papers addressing frequent attendance in primary health care among elderly individuals. Quality of studies was assessed using established criteria for evaluating methodological quality.ResultsTen studies met inclusion criteria and were included for detailed analysis. The average number of patients frequently utilizing primary care services varied across studies from 10% to 33% of the elderly samples and subsamples. The definition of frequent attendance across studies differed substantially. The most consistent associations between frequent attendance and old age were found for presence and severity of physical illness. Results on mental disorders and frequent attendance were heterogeneous. Only a few studies have assessed frequent attendance in association with factors such as drug use, social support or sociodemographic aspects; however results were inconsistent.ConclusionsSevere ill health and the need for treatment serve as the main drivers of frequent attendance in older adults. As results were scarce and divergent, future studies are needed to provide more information on this topic. Since prior studies have offered only a snapshot of this service use behaviour, a longitudinal approach would be preferable in the future.Electronic supplementary materialThe online version of this article (10.1186/s12875-017-0700-7) contains supplementary material, which is available to authorized users.

The cellular response to heat stress is an ancient and evolutionarily highly conserved defence mechanism characterised by the transcriptional up-regulation of cyto-protective genes and a partial inhibition of splicing. These features closely resemble the proteotoxic stress response during tumor development. The bromodomain protein BRD4 has been identified as an integral member of the oxidative stress as well as of the inflammatory response, mainly due to its role in the transcriptional regulation process. In addition, there are also several lines of evidence implicating BRD4 in the splicing process. Using RNA-sequencing we found a significant increase in splicing inhibition, in particular intron retentions (IR), following heat treatment in BRD4-depleted cells. This leads to a decrease of mRNA abundancy of the affected transcripts, most likely due to premature termination codons. Subsequent experiments revealed that BRD4 interacts with the heat shock factor 1 (HSF1) such that under heat stress BRD4 is recruited to nuclear stress bodies and non-coding SatIII RNA transcripts are up-regulated. These findings implicate BRD4 as an important regulator of splicing during heat stress. Our data which links BRD4 to the stress induced splicing process may provide novel mechanisms of BRD4 inhibitors in regard to anti-cancer therapies.

BackgroundObesity is one of the most prevalent health problems in western societies. However, it seems not effectively managed in the healthcare system at present. Originating from smoking cessation a tool called the 5As for obesity management has been drafted and adapted by the Canadian Obesity Network (CON) to improve weight counseling and provider-patient-interaction. This paper describes the rationale and design of the INTERACT study. The objective of the INTERACT study is to evaluate the effectiveness and intervention costs of a 5As eLearning program for obesity management aimed specifically at general practitioners (GPs).MethodsThe INTERACT study is a cluster randomized controlled trial aimed at implementing and evaluating an online-tutorial for obesity management based on the 5As approach in cooperating primary health care practices. Effectiveness of the 5As intervention will be evaluated by assessing patients and doctors perspectives on obesity management in primary care before and after the training. GPs in the intervention group will get access to the 5As obesity management online-tutorial while GPs in the control group will be assigned to a waiting list. Outcome measures for patients and GPs will be compared between the intervention group (treatment as usual + training of the GP) and the control group (treatment as usual). Hierarchical regression models will be used to analyze effects over time pre- and post-intervention.DiscussionThe 5As present physicians with a simple mnemonic for patient counseling in the primary care context. While the use of the 5As in weight counseling seems to be associated with improved doctor-patient interaction and motivation to lose weight, intervention studies assessing the effectiveness of a short 5A eLearning tutorial for physicians on secondary outcomes, such as weight development, are lacking.Trial registrationThe study has been registered at the German Clinical Trials Register (DRKS00009241; date of registration: 03.02.2016).

Background: Anxiety in adults is a common mental health problem. However, studies on anxiety in the oldest-old are lacking. We sought to identify the age- and gender-specific prevalence of anxiety symptoms in a large sample of general practice patients. Furthermore, we investigated relevant associations of anxiety specifically with respect to recent experience of loss. Methods: Based on the German Study on Ageing, Cognition and Dementia in general practice patients, a sample of 897 patients aged 82 years and older was assessed. Anxiety was assessed using the short form of the Geriatric Anxiety Inventory (GAI-SF). For the assessment of loss, patients were asked whether there were cases of death in their closer social environment since the last assessment. Descriptive and logistic regression analyses were run. Results: Of the oldest-old individuals (aged 82+ years, mean age: 86.8), 14.5% (95% CI 12.4–16.8) suffered from anxiety symptoms. Highest prevalence rates were found for 82- to 85-year-old women (17.2%, 95% CI 12.6–22.1) and for 86- to 90-year-old patients (both sexes) in general (15.9%, 95% CI 12.6–19.2). Older individuals who experienced cases of death in their close social environment within the last 18 months had almost twice the odds [odds ratio (OR) 1.91, 95% confidence interval (CI) 1.15–3.17] of reporting anxiety compared to those without a recent loss. As expected, depression and impaired cognitive status were associated with the presence of anxiety symptoms. No relation was found between social network, gender, age, frailty, or physical illness and anxiety in regression analysis. Conclusions: This study provides for the first time age- and gender-specific prevalence rates of anxiety symptoms and associated risk factors among a large population-based sample of oldest-old primary care attenders. Anxiety is highly prevalent in individuals aged 82 years and older. Depression, impaired cognitive status, and recent experience of loss are associated with late-life anxiety. Our findings support the idea that recent experience of loss should be taken seriously in the context of clinical practice with respect to diagnosing and treating anxiety in old age.