Elevated fecal calprotectin is associated with gut microbial dysbiosis, altered serum markers and clinical outcomes in older individuals.

Fecal calprotectin is an established marker of gut inflammation in inflammatory bowel disease (IBD). Elevated levels of fecal calprotectin as well as gut microbial dysbiosis have also been observed in other clinical conditions. However, systemic and multi-omics alterations linked to elevated fecal calprotectin in older individuals remain unclear. This study comprehensively investigated the relationship between fecal calprotectin levels, gut microbiome composition, serum inflammation and targeted metabolomics markers, and relevant lifestyle and medical data in a large sample of older individuals (n = 735; mean age ± SD: 68.7 ± 6.3) from the TREND cohort study. Low (0-50 µg/g; n = 602), moderate (> 50-100 µg/g; n = 64) and high (> 100 µg/g; n = 62) fecal calprotectin groups were stratified. Several pro-inflammatory gut microbial genera were significantly increased and short-chain fatty acid producing genera were decreased in high vs. low calprotectin groups. In serum, IL-17C, CCL19 and the toxic metabolite indoxyl sulfate were increased in high vs. low fecal calprotectin groups. These changes were partially mediated by the gut microbiota. Moreover, the high fecal calprotectin group showed increased BMI and a higher disease prevalence of heart attack and obesity. Our findings contribute to the understanding of fecal calprotectin as a marker of gut dysbiosis and its broader systemic and clinical implications in older individuals.

Introducing a machine learning algorithm for delirium prediction-the Supporting SURgery with GEriatric Co-Management and AI project (SURGE-Ahead).

INTRODUCTION: Post-operative delirium (POD) is a common complication in older patients, with an incidence of 14-56%. To implement preventative procedures, it is necessary to identify patients at risk for POD. In the present study, we aimed to develop a machine learning (ML) model for POD prediction in older patients, in close cooperation with the PAWEL (patient safety, cost-effectiveness and quality of life in elective surgery) project. METHODS: The model was trained on the PAWEL study's dataset of 878 patients (no intervention, age ≥ 70, 209 with POD). Presence of POD was determined by the Confusion Assessment Method and a chart review. We selected 15 features based on domain knowledge, ethical considerations and a recursive feature elimination. A logistic regression and a linear support vector machine (SVM) were trained, and evaluated using receiver operator characteristics (ROC). RESULTS: The selected features were American Society of Anesthesiologists score, multimorbidity, cut-to-suture time, estimated glomerular filtration rate, polypharmacy, use of cardio-pulmonary bypass, the Montreal cognitive assessment subscores 'memory', 'orientation' and 'verbal fluency', pre-existing dementia, clinical frailty scale, age, recent falls, post-operative isolation and pre-operative benzodiazepines. The linear SVM performed best, with an ROC area under the curve of 0.82 [95% CI 0.78-0.85] in the training set, 0.81 [95% CI 0.71-0.88] in the test set and 0.76 [95% CI 0.71-0.79] in a cross-centre validation. CONCLUSION: We present a clinically useful and explainable ML model for POD prediction. The model will be deployed in the Supporting SURgery with GEriatric Co-Management and AI project.

Detecting Misfolded α-Synuclein in Blood Years before the Diagnosis of Parkinson's Disease.

BACKGROUND: Identifying individuals with Parkinson's disease (PD) already in the prodromal phase of the disease has become a priority objective for opening a window for early disease-modifying therapies. OBJECTIVE: The aim was to evaluate a blood-based α-synuclein seed amplification assay (α-syn SAA) as a novel biomarker for diagnosing PD in the prodromal phase. METHODS: In the TREND study (University of Tuebingen) biennial blood samples of n = 1201 individuals with/without increased risk for PD were taken prospectively over 4 to 10 years. We retrospectively analyzed blood samples of 12 participants later diagnosed with PD during the study to detect and amplify pathological α-syn conformers derived from neuronal extracellular vesicles using (1) immunoblot analyses with an antibody against these conformers and (2) an α-syn-SAA. Additionally, blood samples of n = 13 healthy individuals from the TREND cohort and n = 20 individuals with isolated rapid eye movement sleep behavior disorder (iRBD) from the University Hospital Cologne were analyzed. RESULTS: All individuals with PD showed positive immunoblots and a positive α-syn SAA at the time of diagnosis. Moreover, all PD patients showed a positive α-syn SAA 1 to 10 years before clinical diagnosis. In the iRBD cohort, 30% showed a positive α-syn SAA. All healthy controls had a negative SAA. CONCLUSIONS: We here demonstrate the possibility to detect and amplify pathological α-syn conformers in peripheral blood up to 10 years before the clinical diagnosis of PD in individuals with and without iRBD. The findings of this study indicate that this blood-based α-syn SAA assay has the potential to serve as a diagnostic biomarker for prodromal PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Shape variation in modern human upper premolars.

Morphological variation in modern human dentition is still an open field of study. The understanding of dental shape and metrics is relevant for the advancement of human biology and evolution and is thus of interest in the fields of dental anthropology, as well as human anatomy and medicine. Of concern is also the variation of the inner aspects of the crown which can be investigated using the tools and methods of virtual anthropology. In this study, we explored inter- and intra-population morphometric variation of modern humans' upper third and fourth premolars (P3s and P4s, respectively) considering both the inner and outer aspects of the crown, and discrete traits. We worked by means of geometric morphometrics on 3D image data from a geographically balanced sample of human populations from five continents, to analyse the shape of the dentinal crown, and the crown outline in 78 P3s and 76 P4s from 85 individuals. For the study of dental traits, we referred to the Arizona State University Dental Anthropology System integrated with more recent classification systems. The 3D shape variation of upper premolar crowns varied between short and mesio-distally broad, and tall and mesio-distally narrow. The observed shape variation was independent from the geographical origin of the populations, and resulted in extensive overlap. We noted a high pairwise correlation (r1 = 0.83) between upper P3s and P4s. We did not find any significant geographic differences in the analysed non-metric traits. Our outcomes thus suggest that geographical provenance does not play a determinant role in the shaping of the dental crown, whose genesis is under strict genetic control.

Longitudinal cognitive decline characterizes the profile of non-PD-manifest GBA1 mutation carriers.

With disease-modifying treatment for Parkinson's disease (PD) associated with variants in the glucocerebrosidase gene (GBA1) under way, the challenge to design clinical trials with non-PD-manifest GBA mutation carriers (GBA1NMC) comes within close reach. To delineate trajectories of motor and non-motor markers as well as serum neurofilament light (sNfL) levels and to evaluate clinical endpoints as outcomes for clinical trials in GBA1NMC, longitudinal data of 56 GBA1NMC carriers and 112 age- and sex-matched GBA1 wildtype participants (GBA1wildtype) with up to 9 years of follow-up was analyzed using linear mixed-effects models (LMEM) and Kaplan-Meier survival analysis of clinical endpoints for motor and cognitive function. GBA1NMC showed worse performance in Pegboard, 20 m fast walking, global cognition as well as in executive and memory function at baseline. Longitudinally, LMEM revealed a higher annual increase of the MDS-UPDRS III bradykinesia subscore in GBA1NMC compared to GBA1wildtype, but comparable trajectories of all other motor and non-motor markers as well as sNfL. Kaplan-Meier survival analysis showed a significantly earlier progression to clinical endpoints of cognitive decline in GBA1NMC. Incidence of PD was significantly higher in GBA1NMC. In conclusion, our study extends data on GBA1NMC indicating early cognitive decline as a potentially characteristic feature. Comprehensive longitudinal assessments of cognitive function are crucial to delineate the evolution of early changes in GBA1NMC enabling a more accurate stratification and allow for a more precise definition of trial design and sample size.

Physical Activity, Sedentary Behavior, and Their Predictors Among Nursing Home Residents-Cross-Sectional Results of the BaSAlt Study.

Little is known about physical activity (PA) and sedentary behavior (SB) among nursing home residents although PA is known as a health promoter. This study examined PA, SB, and their predictors among nursing home residents (n = 63). Dependent variables were accelerometry-based PA and SB. Predictor variables included in a path analysis were age, sex, body mass index, Barthel Index, cognitive status (Mini-Mental State Examination), physical performance (hand grip strength and habitual walking speed), and well-being (World Health Organization-5 well-being index). PA was very low (M steps per day = 2,433) and SB was high (M percentage of sedentary time = 89.4%). PA was significantly predicted by age (ß = -0.27, p = .008), body mass index (ß = -0.29, p = .002), Barthel Index (ß = 0.24, p = .040), and hand grip strength (ß = 0.30, p = .048). SB was significantly predicted by body mass index (ß = 0.27, p = .008) and Barthel Index (ß = -0.30, p = .012). Results might be helpful for everyday practice to identify individuals at high risk for low PA and high SB.

A 10-step participatory program for developing, implementing, and evaluating physical activity promoting actions in nursing homes in Germany.

BACKGROUND: Since multidimensional barriers challenge nursing homes, a socio-ecological approach is needed for physical activity promotion in this setting. So far, little is known about how such an approach can be transferred into the successful development and implementation of PA-promoting actions together with stakeholders on-site. We aimed to investigate the actions and dimensions of PA-promoting actions and their sustainable implementation. To contribute to closing this gap, we present a 10-step program for co-developing and co-evaluating PA-promoting actions in nursing homes through an integrated counselling approach. METHODS: We used a multiple case study approach that built upon manifold data sources, collected in 7 nursing homes over 3 years between 2021 and 2023. We collected fieldnotes and photologs from 14 future workshops (2 per home); 7 evaluation workshops (1 per home); 36 individual counsellings (2 sessions per resident), as well as 87 implementation protocols (action type and frequency), 11 evaluation questionnaires (changes among resources, cooperations, and collaborations); 7 goal attainment scales and 18 individual activity schedules. In addition, we retrieved and documented progress information at regular intervals by phone or email. RESULTS: With staff, residents, relatives, and volunteers, we co-developed 112 ideas for PA promotion; from which 54 ideas were implemented and integrated into everyday life, differentiated into "activities of daily living," "structured activities," and "activity-friendly environments."; 18 residents in 4 homes participated in individual counselling to develop individual activity schedules. Eighteen actions were rated as "(much) more successful than expected"; 10 "(much) worse than expected," and 23 "as successful as expected." Three actions were not evaluated. DISCUSSION: The participatory integrated counselling approach led to home-specific actions and promoted implementation into everyday life. The number and dimensions of actions implemented largely depended on the mission and vision of the respective home. The lack of staff could partially be compensated for by involving neighbourhoods, volunteers, and community organisations, such as local clubs. CONCLUSION: To effectively promote PA in nursing homes, a tailored approach considering structural conditions, locations, volunteer engagement, and organisational visions is essential. Long-lasting partnerships and low-threshold opportunities prove promising. Future research should delve into structural-level change processes and outcomes in this context.

[Sarcopenia, physical activity and sedentary behavior among nursing home residents in Germany]. / Sarkopenie, körperliche Aktivität und sedentäres Verhalten von Pflegeheimbewohnenden in Deutschland.

BACKGROUND: Residents in nursing homes show a high prevalence of the musculoskeletal syndrome sarcopenia and tend not to achieve current physical activity recommendations. OBJECTIVE: The aim of this study is to identify differences in physical activity and sedentary behavior of sarcopenic residents compared with nonsarcopenic and presarcopenic residents. METHODS: Sarcopenia assessment was performed among 63 nursing home residents in Baden-Wuerttemberg (D) using the European Working Group on Sarcopenia in Older People 2 specifications. Structured activity sessions (per week), accelerometer-based physical activity (steps/day), and sedentary behavior (percentual/day) were examined. The group comparisons were determined with Kruskal-Wallis tests and Dunn-Bonferroni post hoc tests. RESULTS: Significant differences were found for number of steps (p = 0.005) and percentual sedentary behavior (p = 0.019). Moreover, steps per day presented significant results in group comparison for no sarcopenia (2824.4 [423-14275]) with probable sarcopenia (1703.9 [118-5663]) and confirmed/severe sarcopenia (1571.2 [240-2392]) (both p = 0.022; |r| = 0.34). Sedentary behavior demonstrated significant differences in groups with no sarcopenia (87.9% [69.1-94.3]) and with probable sarcopenia (91.7% [80.4-9835]) (p = 0.018; |r| = 0.35). CONCLUSION: Nonsarcopenic residents demonstrated a higher number of steps and lower sedentary behavior compared with presarcopenic and sarcopenic residents. Increasing steps, reducing sedentary behavior and promoting activities of daily living can contribute to the prevention and treatment of sarcopenia in the nursing home setting.

Patterns of physical activity among nursing home residents before and during the Covid 19 pandemic-a systematic observation.

BACKGROUND: The Covid-19 outbreak in spring of 2020 posed an array of challenges for nursing homes, including promoting resident physical activity (PA). Given the diversity of factors affecting resident PA, we explored how activity patterns outside weekly-scheduled structured activities changed during the pandemic and what factors promoted or inhibited PA during the pandemic. METHODS: We conducted systematic direct observations over 823.5 h in eight nursing homes in Southern Germany in 2020 and 2021. RESULTS: In 2020, 84.7% of person observation units were classified as sedentary (average activity level: 1.14 MET). In 2021, the percentage increased to 91.6% of observed person units (average activity level: 1.08 MET) (t = 6.947; p = .000). According to tree classification, influencing factors of PA included mealtime and daytime in 2020 and 2021, as well as presence of men residents only in 2020 and guided low threshold activities in 2021. CONCLUSIONS: Nursing homes constitute highly sedentary places-an issue exacerbated by access restrictions for external activity experts and significant others as well as behavioural restrictions for residents during the Covid-19 pandemic. Staff could not compensate due to existing time restraints and lack of training in PA promotion. Based on our findings, we recommend future studies to develop feasible and resource-low activities to be integrated into the daily routines of nursing homes.

Modular Cluster Circuits for the Variational Quantum Eigensolver.

The variational quantum eigensolver algorithm recently became a popular method to compute the quantum chemical properties of molecules on noisy intermediate scale quantum (NISQ) devices. In order to avoid noise accumulation from the NISQ device in the quantum circuit, it is important to keep the so-called quantum depth of the circuit at a minimum, defined as the minimum number of quantum gates that must be operated sequentially. In the present work, we introduce a modular 2-qubit cluster circuit that allows for the design of a shallow-depth quantum circuit compared to previously proposed architectures without loss of chemical accuracy. Moreover, by virtue of the simplicity of the cluster circuit, it is possible to assign a valence bond chemical interpretation to the cluster circuit. The design was tested on the H2, (H2)2, and LiH molecules, as well as the finite-size transverse-field Ising model, as the latter provides additional insights into the construction of the circuit in a resonating valence bond picture.

Older adults' coping strategies during the COVID-19 pandemic - a longitudinal mixed-methods study.

Introduction: Older age is a main risk factor for severe COVID-19. In 2020, a broad political debate was initiated as to what extent older adults need special protection and isolation to minimize their risk for SARS-CoV-2 infection. However, isolation might also have indirect negative psychological (e.g., loneliness, stress, fear, anxiety, depression) or physical (e.g., lack of exercise, missing medical visits) consequences depending on individual strategies and personality traits to cope longitudinally with this crisis. Methods: To examine the impact of individuals' coping with the pandemic on mental health, a large sample of 880 older adults of the prospective longitudinal cohort TREND study were surveyed six times about their individual coping strategies in the COVID-19 pandemic between May 2020 (05/2020: Mage = 72.1, SDage = 6.4, Range: 58-91 years) and November 2022 in an open response format. The relevant survey question was: "What was helpful for you to get through the last months despite the COVID-19 pandemic? E.g., phone calls, going for a walk, or others." Results and Discussion: In total, we obtained 4,561 records containing 20,578 text passages that were coded and assigned to 427 distinct categories on seven levels based on qualitative content analysis using MAXQDA. The results allow new insights into the impact of personal prerequisites (e.g., value beliefs, living conditions), the general evaluation of the pandemic (e.g., positive, irrelevant, stressful) as well as the applied coping strategies (e.g., cognitive, emotional- or problem-focused) to deal with the COVID-19 pandemic by using an adapted Lazarus stress model. Throughout the pandemic emotional-focused as well as problem-focused strategies were the main coping strategies, whereas general beliefs, general living conditions and the evaluation were mentioned less frequently.

Quantum Leaps in Human Biocultural Evolution and the Relationship to Cranial Capacity.

The evolution of the genus Homo can only be understood by considering both of the inheritance systems that interact to shape human nature: biology and culture. While growing intellectual abilities are a key factor of human evolution, they are rarely contrasted with cultural progress. Cranial capacity data of 193 hominin fossils from the last seven million years and artefacts of increasing number and complexity in the archaeological record are used to demonstrate the concordant progression of brain-size increase and cultural development, starting approximately two million years ago. Our biocultural evolution shows a number of quantum leaps along the time axis applying to both domains. At first, humans left the canonical evolutionary pathway, which pertains to all other organisms, by enhancing their fitness using sophisticated tools and fire; secondly, they turned into a symbolic species; and finally, humanity now faces a new challenge: "intentional evolution". Chronologically, these quantum leaps correspond to cranial capacity data used here as a proxy for cognitive performance. This contribution tries to demonstrate this parallel development and argues for a simple and generalized model of human biocultural evolution. An extrapolation of the model into the future shows that humans, as biological entities, will not necessarily persist.

The relationship between pre-surgery self-rated health and changes in functional and mental health in older adults: insights from a prospective observational study.

BACKGROUND: Elective surgeries are among the most common health stressors in later life and put a significant risk at functional and mental health, making them an important target of research into healthy aging and physical resilience. Large-scale longitudinal research mostly conducted in non-clinical samples provided support of the predictive value of self-rated health (SRH) for both functional and mental health. Thus, SRH may have the potential to predict favorable adaptation processes after significant health stressors, that is, physical resilience. So far, a study examining the interplay between SRH, functional and mental health and their relative importance for health changes in the context of health stressors was missing. The present study aimed at addressing this gap. METHODS: We used prospective data of 1,580 inpatients (794 complete cases) aged 70 years or older of the PAWEL study, collected between October 2017 and May 2019 in Germany. Our analyses were based on SRH, functional health (Barthel Index) and self-reported mental health problems (PHQ-4) before and 12 months after major elective surgery. To examine changes and interrelationships in these health indicators, bivariate latent change score (BLCS) models were applied. RESULTS: Our analyses provided evidence for improvements of SRH, functional and mental health from pre-to-post surgery. BLCS models based on complete cases and the total sample pointed to a complex interplay of SRH, functional health and mental health with bidirectional coupling effects. Better pre-surgery SRH was associated with improvements in functional and mental health, and better pre-surgery functional health and mental health were associated with improvements in SRH from pre-to-post surgery. Effects of pre-surgery SRH on changes in functional health were smaller than those of functional health on changes in SRH. CONCLUSIONS: Meaningful changes of SRH, functional and mental health and their interplay could be depicted for the first time in a clinical setting. Our findings provide preliminary support for SRH as a physical resilience factor being associated with improvements in other health indicators after health stressors. Longitudinal studies with more timepoints are needed to fully understand the predictive value of SRH for multidimensional health. TRIAL REGISTRATION: PAWEL study, German Clinical Trials Register, number DRKS00013311. Registered 10 November 2017 - Retrospectively registered, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013311 .

Bayesian network modeling of risk and prodromal markers of Parkinson's disease.

Parkinson's disease (PD) is characterized by a long prodromal phase with a multitude of markers indicating an increased PD risk prior to clinical diagnosis based on motor symptoms. Current PD prediction models do not consider interdependencies of single predictors, lack differentiation by subtypes of prodromal PD, and may be limited and potentially biased by confounding factors, unspecific assessment methods and restricted access to comprehensive marker data of prospective cohorts. We used prospective data of 18 established risk and prodromal markers of PD in 1178 healthy, PD-free individuals and 24 incident PD cases collected longitudinally in the Tübingen evaluation of Risk factors for Early detection of NeuroDegeneration (TREND) study at 4 visits over up to 10 years. We employed artificial intelligence (AI) to learn and quantify PD marker interdependencies via a Bayesian network (BN) with probabilistic confidence estimation using bootstrapping. The BN was employed to generate a synthetic cohort and individual marker profiles. Robust interdependencies were observed for BN edges from age to subthreshold parkinsonism and urinary dysfunction, sex to substantia nigra hyperechogenicity, depression, non-smoking and to constipation; depression to symptomatic hypotension and excessive daytime somnolence; solvent exposure to cognitive deficits and to physical inactivity; and non-smoking to physical inactivity. Conversion to PD was interdependent with prior subthreshold parkinsonism, sex and substantia nigra hyperechogenicity. Several additional interdependencies with lower probabilistic confidence were identified. Synthetic subjects generated via the BN based representation of the TREND study were realistic as assessed through multiple comparison approaches of real and synthetic data. Altogether our work demonstrates the potential of modern AI approaches (specifically BNs) both for modelling and understanding interdependencies between PD risk and prodromal markers, which are so far not accounted for in PD prediction models, as well as for generating realistic synthetic data.

Frailty index and its association with the onset of postoperative delirium in older adults undergoing elective surgery.

BACKGROUND: The association of frailty based on the accumulation of deficits with postoperative delirium (POD) has been poorly examined. We aimed to analyze this association in older patients undergoing elective surgery. METHODS: Preoperative data was used to build a 30-item frailty index (FI) for participants of the PAWEL-study. Delirium was defined by a combination of I-CAM and chart review. Using logistic regressions models we analysed the association between frailty and POD adjusting for age, sex, smoking, alcohol consumption, education and type of surgery. RESULTS: Among 701 participants (mean age 77.1, 52.4% male) median FI was 0.27 (Q1 0.20| Q3 0.34), with 528 (75.3%) frail participants (FI ≥ 0.2). Higher median FI were seen in orthopedic than cardiac surgery patients (0.28 versus 0.23), and in women (0.28 versus 0.25 in men). Frail participants showed a higher POD incidence proportion (25.4% versus 17.9% in non-frail). An increased odds for POD was observed in frail versus non-frail participants (OR 2.14 [95% CI 1.33, 3.44], c-statistic 0.71). A 0.1 increment of FI was associated with OR 1.57 [95% CI 1.30, 1.90] (c-statistic 0.72) for POD. No interaction with sex or type of surgery was detected. Adding timed-up-and-go-test and handgrip strength to the FI did not improve discrimination. CONCLUSION: Our data showed a significant association between frailty defined through a 30-item FI and POD among older adults undergoing elective surgery. Adding functional measures to the FI did not improve discrimination. Hence, our preoperative 30-item FI can help to identify patients with increased odds for POD. TRIAL REGISTRATION: PAWEL and PAWEL-R (sub-) study were registered on the German Clinical Trials Register (number DRKS00013311 and DRKS00012797).

Longitudinal dynamics of depression in risk groups of older individuals during the COVID-19 pandemic.

Background: Older individuals are most at risk of severe COVID-19 and particularly require protection causing (self)restriction of psychosocial interaction in daily living. So far, the impact of psychosocial withdrawal on mental health seems less pronounced in community-dwelling older individuals compared to younger individuals. However, dynamics and adverse long-term effects of the pandemic, such as increases in depression, are still mostly unclear, especially for vulnerable subgroups. Methods: Pre-pandemic and 3-, 8-, 14-, 20-month peri-pandemic data were analyzed in 877 older participants (age at 3-month peri-pandemic: mean ± SD: 72.3 ± 6.3, range: 58-91 years) of the observational prospective TREND study in Germany. Severity of depression (Beck's Depression Inventory-II scores) and key factors of (mental) health were investigated for cross-sectional associations using path modeling. Risk groups defined by resilience, loneliness, history of depression, stress, health status and fear of COVID-19 were investigated for differences in depression between timepoints. Findings: The early pandemic (3-month) severity of depression was most strongly associated with history of depression, stress and resilience. Overall increases in clinically relevant depression (mild-severe) from pre- to 3-month peri-pandemic were small (% with depression at pre-/3-month peri-pandemic: 8.3%/11.5%). Changes were most pronounced in risk groups with low resilience (27.2%/41.8%), loneliness (19.0%/28.9%), fear of COVID-19 (17.6%/31.4%), high stress (24.4%/34.2%), a history of depression (27.7%/36.9%), and low health status (21.8%/31.4%). Changes in depression were largely observed from pre- to 3-month and were sustained to the 20-month peri-pandemic timepoint, overall and in stratified risk groups defined by single and cumulative risk factors. Changes between timepoints were heterogenous as indicated by alluvial diagrams. Conclusion: Only specific risk groups of older individuals showed a large increase in depression during the COVID-19 pandemic. Since these increases occurred early in the pandemic and were sustained over 20 months, these vulnerable risk groups need to be prioritized for counselling and risk mitigation of depression.

Comparison of Habitual and Maximal Gait Speed and their Impact on Sarcopenia Quantification in German Nursing Home Residents.

Objectives: Sarcopenia is characterized by loss of muscle strength and muscle mass. The EWGSOP2 specifications include physical functioning determination for quantification of the sarcopenia severity. However, there is a lack in the use of habitual and maximal gait speed and their influence on sarcopenia quantification. We hypothesize differences in sarcopenia quantification using habitual and maximal gait speed. Methods: Sixty-six residents from five nursing homes were examined. Habitual and maximal gait speed were measured by 4-meter-walking-Test. McNemar-Test and χ2-test were used to identify quantification differences. Effect sizes of both gait speeds were calculated with Spearman's rank-correlation-coefficient. Results: Significant difference was identified for twenty-two residents in physical functioning classification by McNemar-Test (p<.001). χ2-Test identified a significant frequency distribution for sarcopenia categories between both gait speeds (χ2 (df2)=11.215, p=.004; Cramer's V=.412). Significant correlations (p<.05) were only shown for maximal gait speed in variables falls in the last three months (|rs|=.326), Barthel-Index (|rs|=.415), and SARC-F (|rs|=.335). Conclusions: The use of habitual and maximal gait speed has a significant impact on sarcopenia quantification in nursing home residents. An adapted standardization in the EWGSOP2 specifications should follow.

A retrospective study with long term follow-up of Graves' disease patients treated with low activities of 131 Iodine.

BACKGROUND: Previous studies have shown that application of relatively low 131 I-Iodine activities can successfully be used to treat patients with Graves'disease (GD). We assessed treatment outcome in the long-term follow-up of our GD patients and influencing factors. METHODS: We evaluated 521 GD patients in this retrospective clinical single-center study. In all patients we performed scintigraphy and thyroid uptake measurement after 4 h and 24 h using 10 MBq 123 I and calculated administered activity using Marinellis' formula. Treatment was done according to national regulations. Minimal routine clinical evaluation of all patients was available after 6 weeks and after 3, 6 and 12 months. Success of treatment was defined as euthyroid state or hypothyroidism 6 months after therapy. RESULTS: We usually applied relatively low 131 I activities. 307 patients (58.9%) became hypothyroid within 21 years of follow-up. 139 patients (26.7%) became euthyroid and stayed euthyroid until the end of follow-up. We found a plateau after 7 years of initial therapy with only a few patients becoming hypothyroid after that time and identified 75 patients (14.4%) with persistent hyperthyroidism or recurrence. CONCLUSIONS: Treatment with relatively low 131 I activities produce favourable responses as shown in previous works. We found a high proportion of patients with long-term euthyroid state. Application of low activities reduces radiation burden of patients and, depending on radiation protection legislation, may lead to shortened hospital stay and reduced costs. Therefore, we feel that application of higher activities to treat GD patients as recommended in several current guidelines should be reconsidered.

Reaction of lithium hexamethyldisilazide (LiHMDS) with water at ultracold conditions.

Alkali metal amides are highly reactive reagents that are broadly applied as strong bases in organic synthesis. Here, we use a combined helium nanodroplet IR spectroscopic and theoretical (DFT calculation) study to show that the reaction of the model compound lithium hexamethyldisilazide (LiHMDS) with water is close to barrierless even at ultra-cold conditions. Upon complex formation of dimeric (LiHMDS)2 with water in helium nanodroplets as ultra-cold nano-reactors (0.37 K) we observed the reaction product (LiOH)2(HMDS)2. This can be rationalized as aggregation induced reation upon stepwise addition of water. With increasing water partial pressure, only the product (LiOH)2(HMDS)2 is observed experimentally. This implies that the large interaction energy (69 kJ mol-1) of (LiHMDS)2 with water is sufficient to overcome the follow-up reaction barriers, in spite of the rapid cooling rates in He nanodroplets.

A Prospective Study to Evaluate the Impact of Golimumab Therapy on Work Productivity and Activity, and Quality of Life in Patients With Rheumatoid Arthritis, Psoriasis Arthritis and Axial Spondyloarthritis in a Real Life Setting in AUSTRIA. The GO-ACTIVE Study.

Objective: To analyze real-world evidence on work productivity and daily activity impairment (WPAI) and health-related quality of life (HRQoL) in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) patients treated with golimumab in Austria. Methods: This was a prospective, non-interventional, multi-center study conducted in RA, PsA and axSpA patients initiating golimumab between April 2016 and May 2020 in 40 centers in Austria. WPAI, HRQoL (RAQoL, ankylosing spondylitis (AS)QoL and PsAQoL) questionnaires and disease activity (Clinical Disease Activity Index, CDAI, in RA and PsA; Bath Ankylosing Spondylitis Disease Activity Index, BASDAI, in axSpA) were assessed at baseline and months 3, 6, 12, 18, and 24. Association between WPAI and disease activity was tested using linear regression. Results: We enrolled 233 patients (RA, n = 95; axSpA, n = 69; PsA, n = 69), 110 patients were followed up to month 24. Mean age was 50.2 ± 14.2 years; 64% were female. Disease activity decreased from baseline to month 24 (RA: CDAI -24.3 ± 13.5; axSpA: BASDAI -4.4 ± 2.1, and PsA: CDAI -21.7 ± 8.5, p < 0.0001, each). Total work productivity impairment (TWPI), activity impairment and presenteeism subscores continuously decreased throughout month 24 in all indications: RA (-58.3 ± 23%, -62.6 ± 23.8% and -61.7 ± 23.3%, respectively as compared to baseline; p < 0.0001, each), axSpA (-34.4 ± 38.3%, p = 0.0117; -60.9 ± 25.9%, and -43.8 ± 26.6%, respectively, p ≤ 0.0001 both) and PsA (-35.8 ± 43.7%, p = 0.0186; -52.3 ± 25.4%, p < 0.0001; and -43.3 ± 33.5%, p = 0.0007, respectively). Absenteeism scores decreased only in RA patients (-9.2 ± 24.9%, p = 0.0234). HRQoL improved between baseline and month 24 (RAQoL: -12.6 ± 7.5; ASQoL: -8.0 ± 4.3; PsAQoL; -8.3 ± 6.4, p < 0.0001, each). TWPI, presenteeism and activity impairment strongly associated with disease activity throughout the study. Conclusions: This real-world study confirms the benefit of golimumab on work productivity/daily activity impairment in Austrian RA, PsA, and axSpA patients.