Using a brief web-based 5A intervention to improve weight management in primary care: results of a cluster-randomized controlled trial.

BACKGROUND: The primary health care setting is considered a major starting point in successful obesity management. However, research indicates insufficient quality of weight counseling in primary care. Aim of the present study was to implement and evaluate a 5A online tutorial aimed at improving weight management and provider-patient-interaction in primary health care. The online tutorial is a stand-alone low-threshold minimal e-health intervention for general practitioners based on the 5As guidance for obesity management by the Canadian Obesity Network. METHODS: In a cluster-randomized controlled trial, 50 primary care practices included 160 patients aged 18 to 60 years with obesity (BMI ≥ 30). The intervention practices had continuous access to the 5A online tutorial for the general practitioner. Patients of control practices were treated as usual. Primary outcome was the patients' perspective of the doctor-patient-interaction regarding obesity management, assessed with the Patient Assessment of Chronic Illness Care before and after (6/12 months) the training. Treatment effects over time (intention-to-treat) were evaluated using mixed-effects linear regression models. RESULTS: More than half of the physicians (57%) wished for more training offers on obesity counseling. The 5A online tutorial was completed by 76% of the physicians in the intervention practices. Results of the mixed-effects regression analysis showed no treatment effect at 6 months and 12 months' follow-up for the PACIC 5A sum score. Patients with obesity in the intervention group scored lower on self-stigma and readiness for weight management compared to participants in the control group at 6 months' follow-up. However, there were no significant group differences for weight, quality of life, readiness to engage in weight management, self-stigma and depression at 12 months' follow-up. CONCLUSION: To our knowledge, the present study provides the first long-term results for a 5A-based intervention in the context of the German primary care setting. The results suggest that a stand-alone low-threshold minimal e-health intervention for general practitioners does not improve weight management in the long term. To improve weight management in primary care, more comprehensive strategies are needed. However, due to recruitment difficulties the final sample was smaller than intended. This may have contributed to the null results. TRIAL REGISTRATION: The study has been registered at the German Clinical Trials Register (Identifier: DRKS00009241 , Registered 3 February 2016).

Help-seeking for psychological distress and its association with anxiety in the oldest old - results from the AgeQualiDe cohort study.

Objectives: This study aimed to examine aspects of help-seeking for psychological distress and its association with increased anxiety symptoms in the oldest old.Method: Baseline data from AgeQualiDe, a multicenter cohort study of people aged 85 and over recruited in primary care, were analyzed. Help-seeking for psychological distress (items from the Camberwell Assessment of Need for the Elderly) was analyzed using ordinal and logistic regression models as a function of increased anxiety symptoms (Geriatric Anxiety Inventory-Short Form ≥ 3), as well as relevant socio-demographic and health-related covariates.Results:N = 155 (18.1% of the sample) reported having experienced psychological distress recently and were thus included in the analysis. Among those, 26.5% reported experiencing increased anxiety symptoms. On a descriptive level, 76.8% sought informal, 29.0% sought formal, and 18.1% sought no help for psychological distress. In covariate-adjusted regression models, increased anxiety was significantly associated with increased use of informal support (OR: 2.92, 95% CI: 1.31-6.48), but was neither associated with formal (OR: 0.72, 95% CI: 0.26-1.97) nor no help-seeking (OR: 0.28, 95% CI: 0.08-1.05).Conclusion: A large proportion of those experiencing psychological distress sought support from informal sources in this study. Anxiety symptoms in the oldest old were associated with the increased use of informal support, but not formal support or no help-seeking. Training and support for people providing informal help to those with mental health problems should be promoted to reduce a possible burden. However, future research addressing underlying mechanisms is needed.

[E-Mental Health and healthcare apps in Germany]. / E-Mental-Health und digitale Gesundheitsanwendungen in Deutschland.

Digitalization trends are having an impact on mental healthcare. Online interventions can promote mental health and complement existing mental healthcare services. Effective online interventions have been developed for a variety of mental health disorders and, overall, patient and practitioner acceptance of such programs is high. The Digital Healthcare Act provides the legal framework for the use of healthcare apps in German routine care. After approval by the Federal Institute for Drugs and Medical Devices, the costs of certain healthcare apps are now covered by statutory health insurers. However, digital technologies have rarely been used in mental healthcare to date. Reasons include a low level of awareness of such programs as well as a large number of untested applications. Specified quality criteria can provide better orientation for patients and healthcare providers. Further implementation efforts are necessary in order to fully use the potential of digital support options in psychiatric and psychotherapeutic care for the benefit of patients.

[Health-related consequences of social isolation: a qualitative study on psychosocial stress and resources among older adults in the COVID-19 pandemic]. / Gesundheitliche Folgen sozialer Isolation: Qualitative Studie zu psychosozialen Belastungen und Ressourcen älterer Menschen im Zusammenhang mit der COVID-19-Pandemie.

BACKGROUND: The SARS-CoV-2 pandemic led to a general uncertainty about risk and consequences of the disease. Older adults are specifically vulnerable with regard to severe courses of the disease and have been particularly encouraged to self-isolate during the pandemic. Subsequently, expressions of concern have been raised regarding the negative impact of disease risk and quarantine on the mental health of older people. OBJECTIVES: Assessment of psychosocial stress, coping strategies, need for support, and sense of coherence of older people during the COVID-19 pandemic. MATERIALS AND METHODS: The study follows a qualitative research design. Between May and June 2020 N = 11 guided telephone interviews were conducted with older adults (70+ years). Telephone interviews were recorded by audio tape and fully transcribed. A qualitative content analysis was performed according to Mayring and Fenzl (2019) using MAXQDA. RESULTS: Participants were 74.8 years old on average. Participants showed predominantly good psychosocial health and functional coping strategies. Life experience, an optimistic attitude, understanding of the necessity of restrictions, and previous crises that have been mastered were the most important resources during the COVID-19 pandemic for older adults. Offers of support were rarely used. Participants were critical of the closing of centers or meeting points for older people. CONCLUSION: Older adults appear to be able to preserve their mental wellbeing during the COVID-19 pandemic. The relevance of mental resources of older adults for supporting younger generations seems to be unrecognized.

Frequent attendance in primary care in the oldest old: evidence from the AgeCoDe-AgeQualiDe study.

BACKGROUND: There are very few studies examining the determinants of frequent attendance in primary care among the oldest old. AIMS: The purpose of this study was to determine the characteristics of frequent attendance among individuals aged 85 years or older. METHODS: Cross-sectional data stem from the multicenter prospective cohort "Study on needs, health service use, costs and health-related quality of life in a large sample of oldest old primary care patients (85 +)" (AgeQualiDe). This study covers very old primary care patients (n = 861, mean age of 89.0 years ± 2.9; 85-100 years). The number of self-reported GP visits in the preceding 3 months was used to quantify frequent attenders. We defined patients in the top decile as frequent attenders. RESULTS: Multiple logistic regressions showed that frequent attendance was associated with more chronic diseases (adjusted OR 1.12, 95% CI 1.01-1.23), worse functioning (OR 0.97, 95% CI 0.95-0.99), worries about one's financial situation (OR 2.20, 95% CI 1.07-4.53) and it was inversely associated with depression (OR 0.26, 95% CI 0.08-0.80). DISCUSSION: In contrast to studies based on younger samples, different factors were associated with frequent users in our study, showing that it is important to study the determinants of frequent attendance among the oldest old. CONCLUSION: In Germany, among the group of the oldest old, frequent attendance was positively associated with worse physical health status (e.g., number of chronic diseases), but negatively with depression. This might indicate that the German health care system is responsive to the physical, but not psychological needs of the oldest old.

Attitudes and treatment practice of general practitioners towards patients with obesity in primary care.

BACKGROUND: Obesity is one of the most common and relevant health problems in need of urgent action in Germany. General practitioners (GPs) are the initial contact and thus one of the most important starting points for the successful treatment of overweight and obesity. The aim of the study was to assess the treatment practice and attitudes towards patients with obesity in primary health care in Germany. METHODS: Analyses were based on baseline data of the INTERACT trial of 47 GPs in central Germany. Stigmatizing attitudes were identified using the Fat Phobia Scale (FPS). In addition, questionnaires including sociodemographic information, attribution of causes of obesity, referral behavior and clinical activities were completed. Statistical investigations include descriptive analysis, principal component analysis, inference statistics and linear regression models. RESULTS: GPs rated the quality of medical care for patients with obesity in Germany as below average. The FPS score revealed a value of 3.70, showing that GPs' attitudes towards patients with obesity are stigmatizing. Younger GP age, male gender and a lower number of referrals to specialists were associated with higher levels of stigmatizing attitudes. CONCLUSION: Weight-related stigmatization has an impact on medical treatment. Obesity management guides would help to increase knowledge and reduce weight-related stigmatization in primary care, thereby improving medical care for obese and overweight patients.

The bromodomain protein BRD4 regulates splicing during heat shock.

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.

Psychometric properties of the Patient Assessment of Chronic Illness Care measure (PACIC-5A) among patients with obesity.

BACKGROUND: The Patient Assessment of Chronic Illness Care (PACIC-5A) was developed to assess the satisfaction with patient-provider interaction based on the Chronic Care Model. The additional 5A approach (assess, advise, agree, assist, arrange) allows to score behavioral counseling. The aim of the study was to assess the psychometric properties of the German adaptation of the PACIC-5A questionnaire in a sample of general practitioners (GP) patients with obesity. METHODS: Analyses were based on data from the study "Five A's counseling in weight management of obese patients in primary care: a cluster randomized controlled trial (INTERACT)". Data were collected via standardized questionnaires containing the 26-item version of the PACIC-5A questionnaire. A total of 117 patients with obesity were included in the analyses. Statistical procedures comprised descriptive analyses, the calculation of Cronbach's alpha, test-retest analyses and factor analyses in order to assess the psychometric properties including reliability and validity of the PACIC-5A. RESULTS: The patient's mean age was 43.4 years and the sample was mostly female (59%). Middle educational level was found for the majority (78%) and the mean Body Mass Index was 38.9 kg/m2. Descriptive analyses revealed a mean PACIC score of 2.33 and 5A sum score of 2.29. Notable floor effects were found. PACIC-5A showed high level of internal consistency (Cronbach's alphas > 0.9) and exploratory factor analyses resulted in a unidimensional structure. CONCLUSION: The results of this study provide evidence regarding the psychometric properties of the German version of the PACIC-5A used in a sample of GP patients with obesity and make an important contribution to the reliable and valid assessment of the patient-GP interaction with regard to obesity counseling in primary care.

Five A's counseling in weight management of obese patients in primary care: a cluster-randomized controlled trial (INTERACT).

BACKGROUND: Obesity 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). METHODS: The 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. DISCUSSION: The 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 REGISTRATION: The study has been registered at the German Clinical Trials Register ( DRKS00009241 ; date of registration: 03.02.2016).

Frequent attenders in late life in primary care: a systematic review of European studies.

BACKGROUND: High 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. METHODS: We 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. RESULTS: Ten 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. CONCLUSIONS: Severe 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.

Loss and bereavement in late life (60+): Study protocol for a randomized controlled trial regarding an internet-based self-help intervention.

BACKGROUND: The death of a close person is a highly stressful, yet common life event in later life. While most individuals seem to cope well with bereavement, a substantial proportion of older individuals suffer from prolonged grief symptoms. E-mental health interventions have been shown to be efficient for a variety of psychological illnesses. Yet, there is a large research gap of studies with a special focus on older adults. This study protocol describes a randomized controlled trial for an internet-based self-help intervention addressing bereavement and loss in adults aged 60 years and over. The self-management intervention is based on techniques of cognitive behavioral therapy and consists of 8 modules. The objective of the AgE-health study is to evaluate the effectiveness and acceptability of this intervention in comparison to a bibliotherapy control group. METHODS: The AgE-health study aims at implementing a randomized controlled trial. Eligible participants aged 60+ years will be randomly allocated to an intervention group (access to the intervention) or to an active control group (access to bibliotherapy). Primary outcome is the reduction in grief symptoms (13-item Prolonged Grief Inventory); secondary outcomes are depression, social activity and network, quality of life, self-efficacy, satisfaction with the intervention/bibliotherapy, loneliness, acceptability, up-take and adherence. Assessments will take place before the intervention (baseline) as well as 4 months (follow-up 1) after the intervention. DISCUSSION: This study addresses an under-recognized and understudied mental health burden in later life and may add valuable insight into our knowledge about the effectiveness of eHealth interventions for loss and bereavement in late life. To our knowledge, the AgE-health study will be the first randomized controlled trial to evaluate the effectiveness of an internet-based intervention targeting prolonged grief in adults aged 60 years and over. TRIAL REGISTRATION: The study has been registered at the German Clinical Trials Register (Identifier: DRKS00020595, Registered 30th July 2020, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00020595).

The citrullinated/native index of autoantibodies against hnRNP-DL predicts an individual "window of treatment success" in RA patients.

BACKGROUND: There is a need for biomarker to identify patients "at risk" for rheumatoid arthritis (risk-RA) and to better predict the therapeutic response and in this study we tested the hypothesis that novel native and citrullinated heterogeneous nuclear ribonucleoprotein (hnRNP)-DL autoantibodies could be possible biomarkers. METHODS: Using protein macroarray and ELISA, epitope recognition against hnRNP-DL was analysed in sera from different developed RA disease and diagnosed SLE patients. Toll-like receptor (TLR) 7/9 and myeloid differentiation primary response gene 88 (MyD88)-dependency were studied in sera from murine disease models. HnRNP-DL expression in cultivated cells and synovial tissue was analysed by indirect immunofluorescence, immunoblot and immunohistochemistry. RESULTS: HnRNP-DL was highly expressed in stress granules, citrullinated in the rheumatoid joint and targeted by autoantibodies either as native or citrullinated proteins in patient subsets with different developed RA disease. Structural citrullination dependent epitopes (SCEs) of hnRNP-DL were detected in 58% of the SLE patients although 98% of these sera were α-CCP-2-negative. To obtain a specific citrullinated signal value, we subtracted the native antibody value from the citrullinated signal. The citrullinated/native index of autoantibodies against hnRNP-DL (CNDL-Index) was identified as a new value for an "individual window of treatment success" in early RA and for the detection of RF IgM/α-CCP-2 seronegative RA patients (24-46%). Negative CNDL-index was found in SLE patients, risk-RA and early RA cohorts such as EIRA where the majority of these patients are DAS28-responders to methotrexate (MTX) treatment (87%). High positive CNDL-values were associated with more severe RA, shared epitope and parenchymal changes in the lung. Specifically, native α-hnRNP-DL is TLR7/9-dependent, associated with pain and ROC analysis revealed an association to initial MTX or etanercept treatment response, especially in seronegative RA patients. CONCLUSION: CNDL-index defines people at risk to develop RA and the "window of treatment success" thereby closing the sensitivity gap in RA.

Incidence of Anxiety in Latest Life and Risk Factors. Results of the AgeCoDe/AgeQualiDe Study.

Research on anxiety in oldest-old individuals is scarce. Specifically, incidence studies based on large community samples are lacking. The objective of this study is to assess age- and gender-specific incidence rates in a large sample of oldest-old individuals and to identify potential risk factors. The study included data from N = 702 adults aged 81 to 97 years. Anxiety symptoms were identified using the short form of the Geriatric Anxiety Inventory (GAI-SF). Associations of potential risk factors with anxiety incidence were analyzed using Cox proportional hazard models. Out of the N = 702 older adults, N = 77 individuals developed anxiety symptoms during the follow-up period. The incidence rate was 51.3 (95% CI: 41.2-64.1) per 1000 person-years in the overall sample, compared to 58.5 (95% CI: 43.2-72.4) in women and 37.3 (95% CI: 23.6-58.3) in men. Multivariable analysis showed an association of subjective memory complaints (HR: 2.03, 95% CI: 1.16-3.57) and depressive symptoms (HR: 3.20, 95% CI: 1.46-7.01) with incident anxiety in the follow-up. Incident anxiety is highly common in late life. Depressive symptoms and subjective memory complaints are major risk factors of new episodes. Incident anxiety appears to be a response to subjective memory complaints independent of depressive symptoms.

Ataxin-2 interacts with the DEAD/H-box RNA helicase DDX6 and interferes with P-bodies and stress granules.

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.

[Grief and loss in elderly people: A qualitative study regarding the user acceptance of an internet-based self-help program from user and expert perspective]. / Trauer und Verlust bei älteren Menschen: Eine qualitative Studie zur Nutzungsakzeptanz eines internetbasierten Selbsthilfeprogramms aus Betroffenen - und Expertenperspektive.

INTRODUCTION: The loss of a significant other is a stressful life event, especially for older people. The aim of this study was to investigate user acceptance of an internet-based self-help program for mourners aged 60 years and above. Potential access paths as well as barriers of use were to be identified from both users' and experts' perspectives. METHODS: This study is following a qualitative design. Two focus groups were formed consisting of elderly people (60+) with loss experience (N=12) and of experts from the medical care system (N=8). The focus groups were conducted using a discussion guide related to the model of the Unified Theory of Acceptance and Use of Technology (UTAUT). Focus group data were recorded by audio tape and fully transcribed. Qualitative content analysis according to Mayring (2015) was applied using MAXQDA. RESULTS: The mean age of elderly participants with loss experience was 64.5 years, 50 % were women. From the user's perspective, an internet-based self-help program should comprise information regarding grieving, suggestions and motivation for behavioral activation, strengthening self-esteem, and suggestions for dealing with other feelings related to grief (such as guilt). Directions for relatives of mourners as well as faith and spirituality were important topics for users. Elderly participants felt confident to be able to use an internet-based self-help program. Processing time and topic selection should be flexible for the user. Potential access paths included general practitioners and specialists, mourning cafés, or local media. A potential barrier was seen for people who prefer a personal relationship. The average age of participants in the expert focus group was 40.1 years, 87.5 % were female. There was a high user acceptance from the perspective of health care experts with regard to the target group of elderly people (60+). Access paths were seen across all specialist groups working with elderly people (e.g., physicians, occupational therapists, nursing facilities). Lack of guidance was discussed as a potential barrier. DISCUSSION: A key aspect and prerequisite for the use and effectiveness of an internet-based self-help intervention for mourners is user acceptance. Judgments from potential users and experts showed a high user acceptance, but also the need to address age group-specific topics for coping with grief. CONCLUSION: Internet-based self-help interventions can be a promising add-on treatment option for elderly bereaved people. The implementation of such programs should take the access paths mentioned into account in order to inform users and experts about the intervention.

Prevalence of Anxiety Symptoms and Their Association With Loss Experience in a Large Cohort Sample of the Oldest-Old. Results of the AgeCoDe/AgeQualiDe Study.

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.

FOX-2 dependent splicing of ataxin-2 transcript is affected by ataxin-1 overexpression.

Alternative splicing is a fundamental posttranscriptional mechanism for controlling gene expression, and splicing defects have been linked to various human disorders. The splicing factor FOX-2 is part of a main protein interaction hub in a network related to human inherited ataxias, however, its impact remains to be elucidated. Here, we focused on the reported interaction between FOX-2 and ataxin-1, the disease-causing protein in spinocerebellar ataxia type 1. In this line, we further evaluated this interaction by yeast-2-hybrid analyses and co-immunoprecipitation experiments in mammalian cells. Interestingly, we discovered that FOX-2 localization and splicing activity is affected in the presence of nuclear ataxin-1 inclusions. Moreover, we observed that FOX-2 directly interacts with ataxin-2, a protein modulating spinocerebellar ataxia type 1 pathogenesis. Finally, we provide evidence that splicing of pre-mRNA of ataxin-2 depends on FOX-2 activity, since reduction of FOX-2 levels led to increased skipping of exon 18 in ataxin-2 transcripts. Most striking, we observed that ataxin-1 overexpression has an effect on this splicing event as well. Thus, our results demonstrate that FOX-2 is involved in splicing of ataxin-2 transcripts and that this splicing event is altered by overexpression of ataxin-1.