Cross-seeding by prion protein inactivates TDP-43.

A common pathological denominator of various neurodegenerative diseases is the accumulation of protein aggregates. Neurotoxic effects are caused by a loss of the physiological activity of the aggregating protein and/or a gain of toxic function of the misfolded protein conformers. In transmissible spongiform encephalopathies or prion diseases, neurodegeneration is caused by aberrantly folded isoforms of the prion protein (PrP). However, it is poorly understood how pathogenic PrP conformers interfere with neuronal viability. Employing in vitro approaches, cell culture, animal models and patients' brain samples, we show that misfolded PrP can induce aggregation and inactivation of TAR DNA-binding protein-43 (TDP-43). Purified PrP aggregates interact with TDP-43 in vitro and in cells and induce the conversion of soluble TDP-43 into non-dynamic protein assemblies. Similarly, mislocalized PrP conformers in the cytosol bind to and sequester TDP-43 in cytosolic aggregates. As a consequence, TDP-43-dependent splicing activity in the nucleus is significantly decreased, leading to altered protein expression in cells with cytosolic PrP aggregates. Finally, we present evidence for cytosolic TDP-43 aggregates in neurons of transgenic flies expressing mammalian PrP and Creutzfeldt-Jakob disease patients. Our study identified a novel mechanism of how aberrant PrP conformers impair physiological pathways by cross-seeding.

The prevalence and impact of sarcopenia in older cardiac patients undergoing inpatient cardiac rehabilitation - results from a prospective, observational cohort pre-study.

BACKGROUND: The prevalence of sarcopenia and its impact in older patients undergoing inpatient cardiac rehabilitation (iCR) after cardiac procedure has been insufficiently studied. The main aim of this study was to evaluate the prevalence of sarcopenia and quantify the functional capacity of older sarcopenic and non-sarcopenic patients participating in iCR. METHODS: Prospective, observational cohort study within the framework of the ongoing multicenter prehabilitation study "PRECOVERY". A sample of 122 patients ≥75 years undergoing iCR after cardiac procedure were recruited in four German iCR facilities and followed up 3 months later by telephone. At iCR (baseline), the Strength, Assistance with walking, Rise from a chair, Climb stairs and Falls (SARC-F) questionnaire was used to identify sarcopenic patients. In addition, Katz-Index, Clinical Frailty Scale (CFS), handgrip strength (HGS), Short Physical Performance Battery (SPPB) and 6-minute walk distance (6MWD) measured functional capacity and frailty at baseline. Outcomes were prevalence of sarcopenia and the correlation of sarcopenia to functional capacity and frailty at baseline as well as the SARC-F score at follow-up. The Wilcoxon test was applied for pre-post-test analysis. Correlation between sarcopenia and 6MWD, SPPB score and HGS was tested with the eta coefficient with one-way ANOVA. RESULTS: Complete assessments were collected from 101 patients (79.9 ± 4.0 years; 63% male). At baseline, the mean SARC-F score was 2.7 ± 2.1; 35% with sarcopenia. Other baseline results were Katz-Index 5.7 ± 0.9, CFS 3.2 ± 1.4, HGS 24.9 ± 9.9 kg, SPPB score 7.5 ± 3.3 and 6MWD 288.8 ± 136.5 m. Compared to baseline, fewer patients were sarcopenic (23% versus 35%) at follow-up. In the subgroup of sarcopenic patients at baseline (n = 35), pre-post comparison resulted in a significant SARC-F improvement (p = 0.017). There was a significant correlation between sarcopenia measured by SARC-F and poor results in the assessments of functional capacity (p < 0.001; r > 0.546). CONCLUSIONS: The prevalence of sarcopenia in older patients at iCR after cardiac procedure is high (35%) and remains high at follow-up (23%). Sarcopenia screening is important since the diagnosis of sarcopenia in these patients correlates significantly with poor functional capacity. The results indicate that these patients may benefit from prehabilitation aimed at improving perioperative outcomes, increasing functional capacity and mitigating adverse effects. TRIAL REGISTRATION: German Clinical Trials Register (DRKS; http://www.drks.de ; DRKS00032256). Retrospectively registered on 13 July 2023.

[Reference evaluations for estimating prevalence, incidence, and mortality of public health relevant diseases based on routine data]. / Referenzauswertungen für die Schätzung von Prävalenz, Inzidenz und Mortalität Public-Health-relevanter Erkrankungen auf Basis von Routinedaten.

The routine data of all statutorily insured persons according to the Data Transparency Regulation (DaTraV data) represent a promising data source for the recurrent and timely surveillance of non-communicable diseases (NCDs) in Germany. Thereby, it has become apparent that there is a high demand for reference evaluations that enable quick and regularly repeatable analyses on important NCDs. Against this background, ReFern-01 was initiated, a joint project of the Robert Koch Institute (RKI) and the Federal Institute for Drugs and Medical Devices (BfArM). In collaboration with experts from the field of secondary data analysis and healthcare research, reference evaluations for estimating prevalence, incidence, and mortality for important public health-relevant diseases were developed. First, 11 central NCDs were selected by means of an online survey, and initial case definitions were created in conjunction with a literature review. These were then discussed and agreed upon in a virtual workshop. The created reference evaluations (analysis scripts) allow a standardized estimation of the mentioned epidemiological figures, which are comparable over time and regionally. In addition to providing the results, the scripts will be available at the BfArM for further analysis. Provided that remote access to the analysis of the DaTraV data is available in the future, the results of the ReFern project can strengthen the surveillance of NCDs and support public health actors, for example, in the planning and implementation of health promotion and prevention measures at the federal, state, county, and local levels.

Chewing ability and associated factors in older adults in Germany. Results from GEDA 2019/2020-EHIS.

BACKGROUND: Oral well-being is an important component of general well-being and quality of life, as it is greatly influenced by the ability to chew and speak, and thus by central factors of social interaction. Because quality of life and participation are important factors for health in older age, the aim of this article was to examine the chewing ability, including associated factors, for the older population in Germany on the basis of a nationally representative sample. METHODS: Database is the German Health Update (GEDA 2019/2020-EHIS), a population based cross-sectional survey of the Robert Koch Institute. In the telephone interview, participants aged 55 years and older were asked: "Do you have difficulty biting and chewing on hard foods such as a firm apple? Would you say 'no difficulty', 'some difficulty', 'a lot of difficulty' or 'cannot do at all/ unable to do'?" Prevalences and multivariate prevalence ratios (PR) were calculated with 95% confidence intervals (95% CI) from log-Poisson regressions. Sociodemographic, health-, behavioral- and care-related characteristics were investigated as associated factors. RESULTS: The analyses were based on data from 12,944 participants (7,079 women, 5,865 men). The proportion of people with reduced chewing ability was 20.0%; 14.5% had minor difficulty, 5.5% had major difficulty. There were no differences between women and men. The most important associated factors for reduced chewing ability were old age (PR 1.8, 95% CI 1.5-2.1), low socioeconomic status (PR 2.0, 95% CI 1.7-2.5), limitations to usual activities due to health problems (PR 1.9, 1.6-2.2), depressive symptoms (PR 1.7, 1.5-2.1), daily smoking (PR 1.6, 95% CI 1.3-1.8), low dental utilization (PR 1.6, 95% CI 1.4-1.9), and perceived unmet needs for dental care (PR 1.7, 95% CI 1.5-2.1). CONCLUSIONS: One fifth of adults from 55 years of age reported reduced chewing ability. Thus, this is a very common functional limitation in older age. Reduced chewing ability was associated with almost all investigated characteristics. Therefore, its prevention requires a holistic view in the living environment and health care context of older people. Given that chewing ability influences quality of life and social participation, maintaining or improving chewing ability is important for healthy aging.

[Utilization of dental care by adults with and without impairments and disabilities-results of the GEDA 2014/2015-EHIS study]. / Inanspruchnahme zahnmedizinischer Versorgung von Erwachsenen mit und ohne Beeinträchtigungen und Behinderungen ­ Ergebnisse der Studie GEDA 2014/2015-EHIS.

BACKGROUND: Impairments and disabilities can have a negative impact on oral health. However, studies on the oral health of people with impairments and disabilities are rare. This article examines the 12-month prevalence of dental utilization among adults with and without impairments and disabilities in Germany. METHODS: Analyses are based on data from 23,372 persons aged 18 years and older with permanent residency in Germany from the GEDA 2014/2015-EHIS study. Participants were asked when they last visited a dentist or orthodontist on their own behalf - "less than 6 months ago," "6 to less than 12 months ago," "12 months ago or longer," or "never." For the analyses, the first two and the last two response options were combined, giving the 12-month prevalence of dental utilization. RESULTS: Adults with impairments and disabilities were slightly more likely not to have visited a dental practice in the year prior to the survey than adults without impairments and disabilities (21.5% and 18.4%, respectively; p = 0.002). However, the association between the presence of impairments and disabilities and lower dental utilization did not persist after controlling for age, gender, partnership, and socioeconomic status. DISCUSSION: There are hardly any differences in the dental utilization between persons with and without impairments and disabilities. However, due to their poorer oral health on average, it is necessary to consider how the dental care of this very heterogeneous group can be further improved. The analyses point to the need for care and prevention potentials.

[Self-perceived oral health and associated factors among adults in Germany. Results from GEDA 2019/2020-EHIS]. / Selbstwahrgenommene Mundgesundheit und assoziierte Faktoren bei Erwachsenen in Deutschland. Ergebnisse aus GEDA 2019/2020-EHIS.

BACKGROUND AND AIM OF THE WORK: Information on the oral health of the population is important for the assessment of (preventable) disease burden, for the estimation and planning of health resources and costs, and for the evaluation of health inequalities. The aim of this work is to investigate for the first time self-perceived oral health, including associated factors, based on data from a nationally representative sample for the adult population in Germany. MATERIAL AND METHODS: The data basis is the nationwide German Health Update study (GEDA 2019/2020-EHIS, n = 22,708 aged 18 years and older). In the telephone interview, the participants were asked how they would describe the state of their teeth and gums - "very good," "good," "fair," "bad," or "very bad." Sociodemographic, behavioral, and dental characteristics are examined as associated factors. Prevalences and results of multivariate binary logistic regressions (odds ratios, OR) are reported. RESULTS AND DISCUSSION: Of the participants, 71.4% perceived their oral health as very good or good, 28.6% as fair to very bad. Difficulty in chewing and biting on hard foods (OR 4.0), unmet dental care needs (OR 2.3), male gender (OR 1.5), and not consuming fruits and vegetables daily (OR 1.2) were the most important associated factors for fair to very bad self-perceived oral health; for men, low education (OR 2,1), daily smoking (OR 1.6) and not receiving dental care annually (OR 1.4) were also important. From the results, starting points for promoting oral health can be derived.

Unintentional effects of cleaning a crime scene-when the sponge becomes an accomplice in DNA transfer.

DNA transfer in aqueous solutions as well as the persistence of DNA on washed items has become a major subject of research in recent years and is often a significant problem in court. Despite these approaches, the question about the "mobility" of DNA especially in capital offenses cannot be answered in every case, since a variety of scenarios for DNA transfer are possible. The aim of this study was to investigate whether DNA traces could be distributed by cleaning an object. For this purpose, a large table surface and fabric piece were artificially provided with skin contact traces and body fluids (saliva and blood) in two series of experiments and then wiped off with water or with soap water (218 samples in total). These experiments resulted in a clear "carry over" of DNA traces especially for body fluid samples (100% of blood samples and 75% of saliva samples led to a complete profile). The results could be confirmed in a second experimental set-up with 384 samples using different cleaning agents and more intense cleaning actions. Even small amounts of 5-10 µl body fluid led to complete profiles in around 45% of the samples, while 20 µl led to nearly 65% complete profiles. A strong impact of the amount of traces and the chosen surface could be demonstrated, while the active component of the cleaning agent seemed to be of less influence with the explicit exception of chloric agents which rendered almost everything completely DNA-free. In summary, a distribution of DNA traces by wiping or scrubbing an object could be clearly proven.

[Headache, abdominal and back pain in children and adolescents in Germany : Results from KiGGS Wave 2 and trends]. / Kopf­, Bauch- und Rückenschmerzen bei Kindern und Jugendlichen in Deutschland : Ergebnisse aus KiGGS Welle 2 und Trends.

BACKGROUND: Pain not only causes suffering in children and adolescents, but also leads to school absenteeism, medication intake, medical treatment, and an increased risk of recurrent pain in adulthood. OBJECTIVES: Based on data from the nationwide German Health Interview and Examination Survey for Children and Adolescents (KiGGS Wave 2, 2014-2017), the 3­month prevalence of recurrent headache, abdominal and back pain in girls and boys is reported, and is compared with the prevalence from the KiGGS baseline survey (2003-2006). The consequences of recurrent headache were also explored. MATERIALS AND METHODS: Data from >11,000 participants (KiGGS Wave 2) and from >12,000 (KiGGS baseline) participants aged between 3 and 17 years were analyzed. For 3­ to 10-year-olds, parents/guardians answered the questions, while 11- to 17-year-olds provided information themselves. RESULTS: In 3­ to 10-year-olds, recurrent abdominal pain was most prevalent, affecting one third of girls and one quarter of boys. Headache was the most frequent type of pain in 11- to 17-year-olds, affecting almost every second girl and about every third boy. The 3­month prevalence of recurrent headache, abdominal and back pain has increased in girls and boys, especially in the age groups 7 to 10 years and 11 to 13 years. Among recurrent headache sufferers, adolescents take medication almost twice as often as children. CONCLUSIONS: Headache, abdominal, and back pain are still and with increasing prevalence very common symptoms in children and adolescents in Germany. Their prevention requires a holistic view of children's health in the psychosocial living environment, and healthcare context.

Spiritual/Religious Distress Is Associated with Pain Catastrophizing and Interference in Veterans with Chronic Pain.

Objective: Few studies have examined relations between one important aspect of spiritual/religious functioning-spiritual distress-and pain-related outcomes, and none has examined how spiritual distress and depression conjointly relate to chronic pain. The goal of the present study, then, was to examine veterans' spiritual distress as a predictor of two aspects of chronic pain, catastrophizing and interference, testing a mediational model of depression. Design: Four hundred thirty-six patients seeking treatment in a chronic pain management clinic responded to a mailed survey assessing demographics, spiritual distress, depression, pain catastrophizing, and pain interference. Setting: Participants were drawn from a list of patients enrolled in a chronic pain rehabilitation program at a large Midwestern Veterans Affairs health care system. Subjects: Participants were 436 veterans seeking chronic pain rehabilitation. The sample was predominantly Caucasian and male. Methods: Survey data were subjected to mediational analysis, assessing both direct effects of spiritual distress on pain outcomes and indirect effects of spiritual distress through depression. Results: Results showed that spiritual distress was moderately strongly related to both pain outcomes. Further, depression mediated links between spiritual distress and pain catastrophizing (partially) and interference (fully). Conclusions: These results have implications for further research in spiritually integrated care as a component of holistic, integrative approaches to the management of chronic pain.

Mode Equivalence of Health Indicators Between Data Collection Modes and Mixed-Mode Survey Designs in Population-Based Health Interview Surveys for Children and Adolescents: Methodological Study.

BACKGROUND: The implementation of an Internet option in an existing public health interview survey using a mixed-mode design is attractive because of lower costs and faster data availability. Additionally, mixed-mode surveys can increase response rates and improve sample composition. However, mixed-mode designs can increase the risk of measurement error (mode effects). OBJECTIVE: This study aimed to determine whether the prevalence rates or mean values of self- and parent-reported health indicators for children and adolescents aged 0-17 years differ between self-administered paper-based questionnaires (SAQ-paper) and self-administered Web-based questionnaires (SAQ-Web), as well as between a single-mode control group and different mixed-mode groups. METHODS: Data were collected for a methodological pilot of the third wave of the "German Health Interview and Examination Survey for Children and Adolescents". Questionnaires were completed by parents or adolescents. A population-based sample of 11,140 children and adolescents aged 0-17 years was randomly allocated to 4 survey designs-a single-mode control group with paper-and-pencil questionnaires only (n=970 parents, n=343 adolescents)-and 3 mixed-mode designs, all of which offered Web-based questionnaire options. In the concurrent mixed-mode design, both questionnaires were offered at the same time (n=946 parents, n=290 adolescents); in the sequential mixed-mode design, the SAQ-Web was sent first, followed by the paper questionnaire along with a reminder (n=854 parents, n=269 adolescents); and in the preselect mixed-mode design, both options were offered and the respondents were asked to request the desired type of questionnaire (n=698 parents, n=292 adolescents). In total, 3468 questionnaires of parents of children aged 0-17 years (SAQ-Web: n=708; SAQ-paper: n=2760) and 1194 questionnaires of adolescents aged 11-17 years (SAQ-Web: n=299; SAQ-paper: n=895) were analyzed. Sociodemographic characteristics and a broad range of health indicators for children and adolescents were compared by survey design and data collection mode by calculating predictive margins from regression models. RESULTS: There were no statistically significant differences in sociodemographic characteristics or health indicators between the single-mode control group and any of the mixed-mode survey designs. Differences in sociodemographic characteristics between SAQ-Web and SAQ-paper were found. Web respondents were more likely to be male, have higher levels of education, and higher household income compared with paper respondents. After adjusting for sociodemographic characteristics, only one of the 38 analyzed health indicators showed different prevalence rates between the data collection modes, with a higher prevalence rate for lifetime alcohol consumption among the online-responding adolescents (P<.001). CONCLUSIONS: These results suggest that mode bias is limited in health interview surveys for children and adolescents using a mixed-mode design with Web-based and paper questionnaires.

[Subjective, physical and mental health of children and adolescents in Thuringia : Representative results of the Thuringia state module in KiGGS wave 1]. / Subjektive, körperliche und psychische Gesundheit von Kindern und Jugendlichen in Thüringen : Repräsentative Ergebnisse des Ländermoduls Thüringen in KiGGS Welle 1.

Children and adolescents from Thuringia have higher health care needs compared with peers in Germany overall. It was investigated whether this is due to a higher disease process. The data basis was the Thuringia state module (2010-2012; n = 4884; 0-17 years), which was conducted in KiGGS wave 1 (2009-2012). The health situation of children and adolescents is described in terms of various indicators of subjective, physical, and mental health. Prevalences with 95% confidence intervals were reported, and with logistic regressions, the significance of the group differences was examined. Whether children and adolescents in Thuringia and Germany overall differ in the examined health indicators, was tested with chi-square tests and the p values are corrected according to Bonferroni. With 93.8%, the majority of children and adolescents in Thuringia had very good or good subjective health. One-fifth of children and adolescents (20.4%) had a chronic illness or a long-standing health condition. Hay fever (13.6%) and atopic dermatitis (17.6%) were the most common medically diagnosed chronic diseases. In addition, one-fifth of children and adolescents (20.6%) had symptoms of mental health problems; a medical ADHD diagnosis was found in 5.6% of children and adolescents in Thuringia. Compared with peers from Germany overall, there were only a few differences in the incidence of disease. According to these results, the higher degree of care provided to Thuringian girls and boys cannot be attributed to a higher incidence of disease. Other factors such as greater parental willingness of utilization or a better supply structure must be taken into account.

[Cancer screening in Germany: availability and participation]. / Krebsfrüherkennungsuntersuchungen in Deutschland: Angebot und Inanspruchnahme.

In Germany, approximately 227,000 women and 249,000 men developed cancer in 2014, and nearly 223,000 patients died from the disease that year. Many cancers are curable or have a very good prognosis when they are diagnosed at an early stage. This is where the concept of early detection examinations comes into play.This article describes the current conditions of and participation in examinations for the early detection of cervical, breast, skin, prostate, and colon cancer as provided by Germany's statutory health services. Participation was derived from claims data from the statutory health insurance system as well as from Germany's mammography screening program (MSP). The survey "German Health Update" (GEDA 2014/2015-EHIS) served as an additional data source. According to the claims data and considering the intended intervals, participation quotas among insured persons who are entitled to participate lie between 16% (colonoscopy) and 48% (Pap test). In 2015, 51.5% of invited women participated in the MSP. The results according to self-reports of the GEDA survey lie in part substantially higher. The results according to the claims data, the MSP, as well as the self-reports suggest that a large part of the population utilizes the examinations. Colon and cervical cancer examinations will be expanded as organized and quality-assured early detection programs with regular invitations and information on benefits and risks. These efforts should contribute to reaching eligible people who have thus far not participated.

[Nutrition, physical activity and substance use in children and adolescents : Representative results of the federal state module Thuringia in KiGGS wave 1]. / Ernährung, Bewegung und Substanzkonsum von Kindern und Jugendlichen : Repräsentative Ergebnisse des Landesmoduls Thüringen in KiGGS Welle 1.

The term health behaviour combines both health-promoting and health-risk components. In this study, the health behaviour of children and adolescents in Thuringia is analysed. The database was a representative subsample of the federal state module Thuringia, which was conducted by the Robert Koch Institute as part of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) wave 1 (2010-2012; n = 4,096; 3-17 years). Health behaviour was described based on nine indicators: fruit and vegetable consumption, soft drink consumption, breakfast at home, physical activity, sport, swimming ability, alcohol consumption, smoking and water pipe consumption (shisha smoking). Prevalence and mean values with 95 % confidence intervals were reported, and based on logistic or linear regression, the significance of the group differences was examined. The results show that 43.4 % of children and adolescents in Thuringia ate fruits and vegetables daily, 44.5 % consumed soft drinks less than once a week, and 67.9 % had breakfast at home every weekday. In addition, 31.0 % of children and adolescents in Thuringia were physically active at least 60 min a day, 69.8 % did sports for at least 2 h a week, and 81.5 % can swim. Additionally, 15.9 % of adolescents in Thuringia had hazardous alcohol consumption, 14.4 % currently smoked, and 20.0 % smoked a water pipe. Differences existed with regard to gender, age, socio-economic status (SES) of the family and residence (urban/rural). In summary, many of the children and adolescents in Thuringia demonstrate relatively positive health behaviour. However, the results also indicate groups at higher risk of unhealthy behaviour, such as children and adolescents from families with low SES.

[Medical and inpatient care in childhood and adolescence : Representative results of the federal state module Thuringia in KiGGS wave 1]. / Ärztliche und stationäre Versorgung im Kindes- und Jugendalter : Repräsentative Ergebnisse des Landesmoduls Thüringen in KiGGS Welle 1.

At a young age, health care is mainly provided by doctors in private practice. In this study, the health care of children and adolescents in Thuringia is analysed. Data base is the federal state module Thuringia (2010-2012, n = 4884; 0-17 years), which was conducted by the Robert Koch Institute as part of KiGGS wave 1 (2009-2012). The health care of children and adolescents is described based on 7 indicators: total medical visits, paediatrician visits, general practitioner visits, hospitalisation, health screening examinations and vaccination against human papillomavirus (HPV). Prevalence and mean values with 95 % confidence intervals were reported, and with logistic and linear regressions, the significance of the group differences was examined. Results show that 93.9 % of children and adolescents aged 0-17 years in Thuringia went in the last 12 months to doctors in private practice; the average number of doctor visits was 6.6 contacts. 75.1 % of 0­ to 17-year-olds were treated by a paediatrician, and 29.9 % visited a general practitioner. In addition, 13.1 % of 0­ to 17-year-olds in Thuringia have spent at least one night in hospital in the last 12 months; the average number of hospital nights was 7.2. With 90.5 %, the majority of the children aged 7-13 years completed the health screening program for children (U3-U9, without U7a). 67.5 % of the 14- to 17-year-old girls were vaccinated against HPV with at least one dose (lifetime prevalence), and 56.3 % have received a full vaccination with 3 doses. In addition, 62.0 % of 14- to 17-year-old girls went at least once to a gynaecologist. There are significant differences by gender, age, socio-economic status and place of residence (urban/rural). In summation, the results indicate a high utilisation rate by children and adolescents in Thuringia. Additionally, the findings point out prevention potentials such as the vaccination against HPV.

Prevalence of gestational diabetes mellitus in Germany: Temporal trend and differences by regional socioeconomic deprivation.

Background: Gestational diabetes mellitus (GDM) increases the risk for adverse pregnancy outcomes. In 2012, a general screening for GDM was introduced in Germany. Methods: The analysis is based on data from the external inpatient quality assurance for obstetrics from the years 2013 to 2021. Women with pregestational diabetes were excluded. GDM was defined either by documentation in the maternity record or by ICD diagnosis O24.4 during hospitalisation. We reported the prevalence stratified by year, maternal age and regional socioeconomic deprivation. Results: The age-standardized prevalence of GDM continuously rose from 4.7 % in 2013 to 8.5 % in 2021. The increase was observed in all age groups. In 2021, this corresponded to 63,563 women with GDM. The prevalence was higher in highly deprived regions than in low deprived regions. Conclusion: A steady increase in GDM prevalence and evidence of health inequalities emphasise the need for primary prevention strategies for GDM.

Evaluation of frailty in geriatric patients undergoing cardiac rehabilitation after cardiac procedure: results of a prospective, cross-sectional study.

BACKGROUND: Frailty is an indicator of a decline in quality of life and functional capacity in cardiac rehabilitation (CR) patients. Currently, there is no standardized assessment tool for frailty used in CR. The aim of this study was to determine if the Clinical Frailty Scale (CFS) is feasible for assessing frailty in CR. METHODS: Prospective, cross-sectional study within the framework of the ongoing multicenter prehabilitation study "PRECOVERY". Patients ≥75 years undergoing CR after cardiac procedure (n=122) were recruited in four German inpatient CR facilities. Assessments included: CFS, Katz-Index, hand grip strength (HGS), Short Physical Performance Battery (SPPB) and six-minute-walk test (6MWT). Outcomes were frailty (CFS≥4) and the correlation of frailty with assessments of functional capacity, activities of daily living and clinical parameters. Statistical analysis included descriptive statistics and correlations, using the spearman correlation coefficient and chi-square test to test for significance. RESULTS: Data from 101 patients (79.9±4.0 years; 63% male) were analyzed. The mean CFS score was 3.2±1.4; 41.6% were defined as frail (CFS≥4). The mean time required to assess the CFS was 0.20 minutes. The findings show that CFS correlates significantly (p<0.001) with the following factors: Katz-Index, HGS, SPPB-Score and 6MWT (r≤-0.575). In addition, CFS correlated with small to moderate effects with co-morbidities (r=0.250), as-needed medications and need for nursing assistance (r≤0.248). CONCLUSIONS: The CFS assessment can be performed in under one minute and it correlates significantly with assessments of functional capacity, activities of daily living and clinical parameters in the CR setting. TRIAL REGISTRATION: German Clinical Trials Register (DRKS; http:// www. drks. de; DRKS00032256). Retrospectively registered on 13 July 2023.

Linear ubiquitination induces NEMO phase separation to activate NF-κB signaling.

The NF-κB essential modulator NEMO is the core regulatory component of the inhibitor of κB kinase complex, which is a critical checkpoint in canonical NF-κB signaling downstream of innate and adaptive immune receptors. In response to various stimuli, such as TNF or IL-1ß, NEMO binds to linear or M1-linked ubiquitin chains generated by LUBAC, promoting its oligomerization and subsequent activation of the associated kinases. Here we show that M1-ubiquitin chains induce phase separation of NEMO and the formation of NEMO assemblies in cells after exposure to IL-1ß. Phase separation is promoted by both binding of NEMO to linear ubiquitin chains and covalent linkage of M1-ubiquitin to NEMO and is essential but not sufficient for its phase separation. Supporting the functional relevance of NEMO phase separation in signaling, a pathogenic NEMO mutant, which is impaired in both binding and linkage to linear ubiquitin chains, does not undergo phase separation and is defective in mediating IL-1ß-induced NF-κB activation.

NEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62.

NEMO is a ubiquitin-binding protein which regulates canonical NF-κB pathway activation in innate immune signaling, cell death regulation and host-pathogen interactions. Here we identify an NF-κB-independent function of NEMO in proteostasis regulation by promoting autophagosomal clearance of protein aggregates. NEMO-deficient cells accumulate misfolded proteins upon proteotoxic stress and are vulnerable to proteostasis challenges. Moreover, a patient with a mutation in the NEMO-encoding IKBKG gene resulting in defective binding of NEMO to linear ubiquitin chains, developed a widespread mixed brain proteinopathy, including α-synuclein, tau and TDP-43 pathology. NEMO amplifies linear ubiquitylation at α-synuclein aggregates and promotes the local concentration of p62 into foci. In vitro, NEMO lowers the threshold concentrations required for ubiquitin-dependent phase transition of p62. In summary, NEMO reshapes the aggregate surface for efficient autophagosomal clearance by providing a mobile phase at the aggregate interphase favoring co-condensation with p62.

Health of people with impairments and disabilities in Germany - Selected indicators from GEDA 2014/2015-EHIS.

A large part of the population is affected by impairments and disabilities. Around 13% of people in Germany have an officially recognised disability, and an estimated 15.6% have an impairment. This article provides an overview of the health of people with impairments and disabilities on the basis of selected indicators. The analyses are based on data from 23,372 participating persons aged 18 and over (12,747 women, 10,625 men) in the GEDA 2014/2015-EHIS study of the Robert Koch Institute (RKI), a nationwide survey of the adult population in Germany. 21.5% of persons with impairments and disabilities rate their health as good or very good, in contrast to 76.0% of persons without impairments and disabilities. Depressive symptoms exist in 27.1% of persons with impairments and disabilities and 7.5% of persons without impairments and disabilities. In part, there were differences in health behaviour, for example, people with impairments and disabilities do less aerobic physical activities and consume alcohol in risky amounts less often. 97.0% of the persons with and 86.1% of the persons without impairments and disabilities make use of outpatient medical services within one year, the former also have a higher inpatient and home care utilisation. Overall, poorer health is found among women than among men with impairments and disabilities, as well as with increasing age. The analyses show the need for prevention, health promotion and health care. Further data is needed to describe the health situation of people with impairments and disabilities.