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Abstract Background Prostate cancer ranks as the second most frequently diagnosed cancer in men worldwide. Recent research highlights the crucial roles IL6ST-mediated signaling pathways play in the development and progression of various cancers, particularly through hyperactivated STAT3 signaling. However, the molecular programs mediated by IL6ST/STAT3 in prostate cancer are poorly understood. Methods To investigate the role of IL6ST signaling, we constitutively activated IL6ST signaling in the prostate epithelium of a Pten-deficient prostate cancer mouse model in vivo and examined IL6ST expression in large cohorts of prostate cancer patients. We complemented these data with in-depth transcriptomic and multiplex histopathological analyses. Results Genetic cell-autonomous activation of the IL6ST receptor in prostate epithelial cells triggers active STAT3 signaling and significantly reduces tumor growth in vivo. Mechanistically, genetic activation of IL6ST signaling mediates senescence via the STAT3/ARF/p53 axis and recruitment of cytotoxic T-cells, ultimately impeding tumor progression. In prostate cancer patients, high IL6ST mRNA expression levels correlate with better recurrence-free survival, increased senescence signals and a transition from an immune-cold to an immune-hot tumor. Conclusions Our findings demonstrate a context-dependent role of IL6ST/STAT3 in carcinogenesis and a tumor-suppressive function in prostate cancer development by inducing senescence and immune cell attraction. We challenge the prevailing concept of blocking IL6ST/STAT3 signaling as a functional prostate cancer treatment and instead propose cell-autonomous IL6ST activation as a novel therapeutic strategy.

Mild psoriasis may be burdensome; if symptoms are inadequately controlled, switching therapy may be warranted. In the Phase 3 NAVIGATE trial, patients with moderate-to-severe plaque psoriasis received ustekinumab for 16 weeks. Patients with inadequate response (Investigator’s Global Assessment [IGA] ≥ 2) were randomized to switch to guselkumab or continue ustekinumab. This post-hoc analysis evaluated the patient subgroup with residual mild psoriasis (IGA = 2) after initial ustekinumab therapy. Outcomes assessed included the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Psoriasis Symptoms and Signs Diary (PSSD). Initially, 871 patients received ustekinumab. At Week 16, 161 randomized patients had residual mild psoriasis (IGA = 2). Among guselkumab- vs ustekinumab-treated patients at Week 28, 59.0% vs 27.7% achieved PASI 90, and 50.0% vs 21.0% achieved DLQI 0/1. Mean changes from baseline in PSSD score were –44 vs –28 and –50 vs –32, respectively, with thresholds of –40 considered clinically meaningful. Mean changes in PSSD itch score were –4.6 vs –2.9, with reductions ≥ 4.0 considered clinically meaningful. Treatment differences were maintained/increased through Week 52. Among patients with residual mild psoriasis after 16 weeks of ustekinumab, those switching to guselkumab had greater improvements in skin clearance, health-related quality of life, and patient-reported symptoms and signs than those continuing ustekinumab.

Background: Case reports indicate a clinical connection between SARS-CoV-2 and thyroid dysfunctions. However, evidence from large population-based registry analyses is sparse, especially in Europe, where iodine deficiency is common. This study aimed to analyze the impact of the COVID-19 pandemic on healthcare provision for thyroid diseases in Austria. Methods: We performed a retrospective, population-based registry analysis of the Austrian health insurance fund database, covering more than 9 million inhabitants. Data from all patients with prescriptions of thyroid-specific drugs and/or inpatient thyroid-related diagnoses from 2017 to 2019 (pre-pandemic years) were compared to 2020 and 2021 (pandemic years; characterized by high numbers of SARS-CoV2 infections and population-wide vaccination strategy). The incidence rates of thyroid medication prescriptions for hypothyroidism and hyperthyroidism were calculated for every year to evaluate the impact of the pandemic. Results: The incidence rate for total thyroid medication prescription was 539.07/100,000 individuals (534.23–543.93 95%CI) in 2018 and declined during the pandemic (2020: 387.19/100,000 (383.12–391.29 95%CI); 2021: 336.90/100,000 (333.11–340.73 95%CI)). Similarly, the incidence rate for levothyroxine prescription was higher pre-pandemic (2018: 465.46/100,000 (460.97–469.98 95%CI) and declined during the pandemic (2020: 348.14/100,000 (344.28–352.03 95%CI); 2021: 300.30/100,000 (296.7–303.91 95%CI). The incidence rates of thiamazole prescriptions (2018: 10.24/100,000 (9.58–10.93 95%CI); 2020: 8.62/100,000 (8.03–9.26 95%CI); 2021: 11.17/100,000 (10.49–11.89 95%CI) were stable. Conclusions: These findings suggest no clinically significant impact of SARS-CoV2 and/or vaccination on thyroid function at a population level.

After a neurological injury, neurorehabilitation aims to restore sensorimotor function of patients. Technological assessments can provide high-quality data on a patient’s performance and support clinical decision making towards the most appropriate therapy. In this study, the ArmeoPower, a robotic exoskeleton for the upper extremities, was used to assess 12 neurological patients and 31 non-disabled participants performing various standardized single joint and frontal plane game-like exercises. From the collected data, kinematic metrics (End-Point Error, Hand-Path Ratio, reaction time, stability, Number of Velocity Peaks, peak, and mean Velocity) and the game score, were calculated and analyzed according to three criteria: the reliability (a), the difference between patients and non-disabled participants (b), as well as the influence of robotic movement assistance (c). In total, 39 metrics were analyzed and the following five most promising assessment variables for different exercises could be identified based on the three above-mentioned criteria: smoothness (RainMug (wrist)), mean speed (RainMug (wrist)), reaction time (Goalkeeper), maximum speed (HighFlyer (elbow)) and accuracy (Connect the dots), with the former showing good validity (rho=0.82, p=0.02) when comparing to the patient’s severity level. The results demonstrate feasibility to extract and analyze various kinematic metrics from the ArmeoPower, which can provide quantitative information about human performance during training and therapy. The generated data increases the understanding of the patient’s movement and can be used in the future in clinical research for better performance evaluation and providing more feedback options, leading towards a more personalized and patient-centric therapy.

Abstract Background Little is known about the exact impact of psoriasis on the disease burden of close relatives and partners of those affected by the disease. Objectives The aim of this single‐centre cross‐sectional study was to evaluate the quality of life in psoriasis patients and the impact of disease on partners and close relatives. Methods 250 plaque‐type psoriasis patients (58.4% males and 41.6% females) with mostly treatment‐controlled disease (mean PASI of 1.7 and Dermatology Life Quality Index (DLQI) of 4.1) were recruited from the Psoriasis Registry Austria (PsoRA) and their close relatives and partners were invited to participate in the study. Patient Family Impact Score (PFIS) was calculated from the FamilyPso questionnaire data to establish categories of disease burden in close relatives and partners. Results Valid FamilyPso questionnaires were returned from 153 (61.2%) close relatives and partners. Correlation analysis revealed a significant association between PASI and DLQI (r = 0.512, p

Cutaneous T-cell lymphomas (CTCL) are a group of lymphoproliferative disorders of skin-homing T cells causing chronic inflammation. These disorders cause impairment of the immune environment, which leads to severe infections and/or sepsis due to dysbiosis. In this study, we elucidated the host-microbial interaction in CTCL that occurs during the phototherapeutic treatment regime and determined whether modulation of the skin microbiota could beneficially affect the course of CTCL. EL4 T-cell lymphoma cells were intradermally grafted on the back of C57BL/6 mice. Animals were treated with conventional therapeutics such as psoralen + UVA (PUVA) or UVB in the presence or absence of topical antibiotic treatment (neomycin, bacitracin, and polymyxin B sulphate) as an adjuvant. Microbial colonisation of the skin was assessed to correlate with disease severity and tumour growth. Triple antibiotic treatment significantly delayed tumour occurrence (p = 0.026), which prolonged the survival of the mice (p = 0.033). Allocation to phototherapeutic agents PUVA, UVB, or none of these, along with antibiotic intervention, reduced the tumour growth significantly (p = 0.0327, p ≤ 0.0001, p ≤ 0.0001 respectively). The beta diversity indices calculated using the Bray−Curtis model showed that the microbial population significantly differed after antibiotic treatment (p = 0.001). Upon modulating the skin microbiome by antibiotic treatment, we saw an increase in commensal Clostridium species, e.g., Lachnospiraceae sp. (p = 0.0008), Ruminococcaceae sp. (p = 0.0001)., Blautia sp. (p = 0.007) and a significant reduction in facultative pathogens Corynebacterium sp. (p = 0.0009), Pelomonas sp. (p = 0.0306), Streptococcus sp. (p ≥ 0.0001), Pseudomonas sp. (p = 0.0358), and Cutibacterium sp. (p = 0.0237). Intriguingly, we observed a significant decrease in Staphylococcus aureus frequency (p = 0.0001) but an increase in the overall detection frequency of the Staphylococcus genus, indicating that antibiotic treatment helped regain the microbial balance and increased the number of non-pathogenic Staphylococcus populations. These study findings show that modulating microbiota by topical antibiotic treatment helps to restore microbial balance by diminishing the numbers of pathogenic microbes, which, in turn, reduces chronic inflammation, delays tumour growth, and increases survival rates in our CTCL model. These findings support the rationale to modulate the microbial milieu during the disease course of CTCL and indicate its therapeutic potential.

Abstract Objective To compare forgetting patterns between patients with temporal lobe (TLE) and generalized (GGE) epilepsies and to assess whether recall is associated with epileptic activity. Methods Thirty‐three patients with TLE (13 left, 17 right, and 3 nonlateralized TLE), 42 patients with GGE, and 57 healthy controls (HCs) were asked to recall words, verbal story material, and the Rey‐Osterrieth complex figure at two delays. Accelerated long‐term forgetting (ALF) was defined by group performance comparable to HCs at 30 min and worse recall than HCs after 4 weeks. ALF was assessed by comparing raw test scores in a two‐way repeated measures analysis of variance (ANOVA) adjusted for the learning capacity. Results Compared to HCs, patients with R‐TLE remembered fewer items of the word list after 30 min as well as after 4 weeks. Patients with L‐TLE and GGE had comparable learning‐adjusted performance to HCs at the 30 min delay but scored less after 4 weeks (group by delay interaction F(3, 124) = 3.2, P = 0.026, ηp2 = 0.07). The epilepsy group (patients with TLE and GGE combined) performed as well as HCs at 30 min but worse after 4 weeks irrespective of experienced seizures during the 4‐week delay or interictal bilateral (TLE) or generalized (GGE) activity before the study. We noted no statistically significant differences between patient and HC verbal story (group by delay interaction F(3, 124) = 0.7, P = 0.570, ηp2 = 0.02) or complex figure (F(3, 124) = 0.8, P = 0.488, ηp2 = 0.02) recall. Significance Our data support verbal and visual memory impairment in both TLE and GGE with different performances between these groups in the task of word recall. We suggest the presence of ALF in patients with GGE and left TLE after adjusting for learning capacity. We could not confirm the influence of epileptic activity on long‐term forgetting patterns. Future studies are required to better define domain‐specific differences in memory impairment in TLE and GGE.

Introduction: Children and adolescents with neurological impairments face reduced participation and independence in daily life activities due to walking difficulties. Existing assistive devices often offer insufficient support, potentially leading to wheelchair dependence and limiting physical activity and daily life engagement. Mobile wearable robots, such as exoskeletons and exosuits, have shown promise in supporting adults during activities of daily living but are underexplored for children.Methods: We conducted a cross-sectional study to examine the potential of a cable-driven exosuit, the Myosuit, to enhance walking efficiency in adolescents with diverse ambulatory impairments. Each participant walked a course including up-hill, down-hill, level ground walking, and stairs ascending and descending, with and without the exosuit’s assistance. We monitored the time and step count to complete the course and the average heart rate and muscle activity. Additionally, we assessed the adolescents’ perspective on the exosuit’s utility using a visual analog scale.Results: Six adolescents completed the study. Although not statistically significant, five participants completed the course with the exosuit’s assistance in reduced time (time reduction range: [-3.87, 17.42]%, p-value: 0.08, effect size: 0.88). The number of steps taken decreased significantly with the Myosuit’s assistance (steps reduction range: [1.07, 15.71]%, p-value: 0.04, effect size: 0.90). Heart rate and muscle activity did not differ between Myosuit-assisted and unassisted conditions (p-value: 0.96 and 0.35, effect size: 0.02 and 0.42, respectively). Participants generally perceived reduced effort and increased safety with the Myosuit’s assistance, especially during tasks involving concentric contractions (e.g., walking uphill). Three participants expressed a willingness to use the Myosuit in daily life, while the others found it heavy or too conspicuous.Discussion: Increased walking speed without increasing physical effort when performing activities of daily living could lead to higher levels of participation and increased functional independence. Despite perceiving the benefits introduced by the exosuit’s assistance, adolescents reported the need for further modification of the device design before using it extensively at home and in the community.

Introduction Many climbers believe that they are stronger in crimp finger position than in open hand position. However, compared to open hand, crimped fingers are associated with higher pulley forces increasing the risk of injuries. Climbing expertise may influence the estimation of strength, i.e., the better the climber, the better the self-assessment. This study therefore aimed to find out whether climbing expertise influences self-assessment of finger flexor strength in half-crimp and in open hand position. Methods Data was collected at the Hands-On Science Booth of the Climbing World Championships in Bern. Participants had to fill out a questionnaire including a self-assessment of their climbing expertise and of their maximum finger strength for both hands as well as both finger positions. Afterwards, maximum finger strength was measured on an instrumented campus board: Participants placed the to-be-measured hand on a self-selected rung (depth of 23 mm) and then tried to transfer as much force as possible from their feet to their fingers. Results The analysis was based on 38 intermediate and 36 advanced climbers. Due to the limited number of participants in the lower grade (n = 0) and elite (n = 2) level, those skill levels were not considered. Advanced climbers generated significantly greater forces than intermediate climbers across all four measured conditions (t-tests, all p < 0.01). For both groups, neither in the dominant nor in the non-dominant hand a significant difference in maximum force was observed, e.g., dominant hand, intermediates: or advanced climbers: . Intermediate climbers did neither over- nor underestimate their strength in half-crimp position compared to open hand (paired t-test, p = 0.91 for dominant, p = 0.077 for non-dominant hand). In contrast to the dominant hand, advanced climbers significantly overestimated their strength in half-crimp position for the non-dominant hand (on average 9%, Cohen’s d 0.64, p < 0.01). Discussion/Conclusion Our results confirm the positive correlation between finger strength and climbing level. We also confirm that on a 23 mm rung, greater forces can be generated with in open hand compared to half-crimp (Winkler et al., 2023). With larger hold depths, force generated in open hand significantly increases (Amca et al., 2012), while for smaller holds, force exerted in half-crimp position exceeds that of open hand (Winkler et al., 2023). Hence, at least for larger holds, we recommend adopting an open hand position as preventive measure against finger injuries. Advanced climbers may tend to inaccurately self-assess their strength due to their greater engagement with peers, potentially leading to the circulation of misinformation. Note that participants were instructed to provide a general self-assessment of their strength rather than for a 23 mm deep rung, i.e., they may have had a smaller hold in mind. References Amca, A. M., Vigouroux, L., Aritan, S., & Berton, E. (2012). Effect of hold depth and grip technique on maximal finger forces in rock climbing. Journal of Sports Sciences, 30(7), 669-677. https://doi.org/10.1080/02640414.2012.658845 Winkler, M., Künzell, S., & Auguste, C. (2023). Competitive performance predictors in speed climbing, bouldering, and lead climbing. Journal of Sport Sciences, 41(8), 736-746. https://doi.org/10.1080/02640414.2023.2239598

Epilepsy is an increasing global neurological health issue. Recently, epidemiological and mechanistic studies have raised concern about cardiac involvement in individuals with epilepsy. This has resulted in the “epileptic heart” concept. Epidemiological data linking epilepsy to cardiovascular disease indicate an increased risk for ventricular and atrial arrhythmias, myocardial infarction, heart failure, and sudden death among individuals with epilepsy. Pathways of this interaction comprise increased prevalence of traditional cardiac risk factors, genetic abnormalities, altered brain circuitry with autonomic imbalance, and antiseizure medications with enzyme-inducing and ionic channel-blocking proprieties. Pathophysiological findings in the atria and ventricles of patients with epilepsy are discussed. Echocardiographic findings and future applications of this tool are reviewed. A risk stratification model and future studies on cardiac risk assessment in individuals with epilepsy are proposed.

BackgroundProlonged critical illness is often accompanied by an impairment of adrenal function, which has been frequently related to conditions complicating patient management. The presumed connection between hypoxia and the pathogenesis of this critical- illness- related corticosteroid insufficiency (CIRCI) might play an important role in patients with severe acute respiratory distress syndrome (ARDS). Since extracorporeal membrane oxygenation (ECMO) is frequently used in ARDS, but data on CIRCI during this condition are scarce, this study reports the behaviour of adrenal function parameters during oxygenation support with veno-venous (vv)ECMO in coronavirus disease 2019 (COVID-19) ARDS.MethodsA total of 11 patients undergoing vvECMO due to COVID-19 ARDS at the Medical University of Vienna, who received no concurrent corticosteroid therapy, were retrospectively included in this study. We analysed the concentrations of cortisol, aldosterone, and angiotensin (Ang) metabolites (Ang I–IV, Ang 1–7, and Ang 1–5) in serum via liquid chromatography/tandem mass spectrometry before, after 1 day, 1 week, and 2 weeks during vvECMO support and conducted correlation analyses between cortisol and parameters of disease severity.ResultsCortisol concentrations appeared to be lowest after initiation of ECMO and progressively increased throughout the study period. Higher concentrations were related to disease severity and correlated markedly with interleukin-6, procalcitonin, pH, base excess, and albumin during the first day of ECMO. Fair correlations during the first day could be observed with calcium, duration of critical illness, and ECMO gas flow. Angiotensin metabolite concentrations were available in a subset of patients and indicated a more homogenous aldosterone response to plasma renin activity after 1 week of ECMO support.ConclusionOxygenation support through vvECMO may lead to a partial recovery of adrenal function over time. In homogenous patient collectives, this novel approach might help to further determine the importance of adrenal stress response in ECMO and the influence of oxygenation support on CIRCI.

Background & Aims: Advanced chronic liver disease (ACLD) may affect thyroid hormone homeostasis. We aimed to analyze the pituitary–thyroid axis in ACLD and the prognostic value of free triiodothyronine (fT3). Methods: Patients with ACLD (liver stiffness measurement [LSM] ≥10 kPa) undergoing hepatic venous pressure gradient (HVPG) measurement between June 2009 and September 2022 and available fT3 levels were included. Clinical stages of ACLD were defined as follows: probable ACLD (pACLD; LSM ≥10 kPa and HVPG ≤5 mmHg), S0 (mild portal hypertension [PH]; HVPG 6–9 mmHg), S1 (clinically significant PH), S2 (clinically significant PH with varices), S3 (past variceal bleeding), S4 (past/current non-bleeding hepatic decompensation), and S5 (further decompensation). Results: Among 297 patients with ACLD, 129 were compensated (pACLD, n = 10; S0, n = 33; S1, n = 42; S2, n = 44), whereas 168 were decompensated (S3, n = 12; S4, n = 97; S5, n = 59). Median levels of thyroid-stimulating hormone (TSH) numerically increased with progressive ACLD stage (from 1.2 μIU/ml [pACLD] to 1.5 μIU/ml [S5]; p = 0.152), whereas fT3 decreased (from 3.2 pg/ml [pACLD] to 2.5 pg/ml [S5]; p

Objective: To elucidate the pathogenesis of dupilumab (Dupixent®)–associated ocular surface disease (DAOSD). Design: Prospective single-center cohort study. Subjects: Twenty patients with moderate-to-severe atopic dermatitis (AD) who received dupilumab and 10 age- and sex-matched healthy controls were enrolled in the study. Methods: The study cohort underwent a thorough slit-lamp and entire-body dermatologic examination. Conjunctival swabs and smears were collected at baseline, 4 and 16 weeks after treatment initiation, and during the conjunctivitis episode. To analyse the ocular surface microbiome, 16S ribosomal RNA sequencing was performed, smears were hematoxylin and eosin stained, and serum cytokines were measured by using a multiplex immunobead assay. Main Outcome Measures: Composition of ocular surface microbiome and cellular component as well as serum cytokine levels. Results: Six of the 20 patients with AD developed DAOSD after dupilumab initiation; these patients responded after a delay to treatment as quantified by Eczema Area and Severity Index and Investigator’s Global Assessment score. Conjunctival smears showed massive neutrophilic infiltration and serum analysis revealed increased systemic levels of neutrophil-priming proinflammatory cytokines, in particular interleukin-1β and tumor necrosis factor α, in patients with DAOSD compared with those without it. The ocular surface microbiome of patients with DAOSD was characterized by a diverse and persistent microbial colonization, particularly by Acetobacter aceti. In contrast, microbial diversity decreased in patients with AD without DAOSD after the initiation of dupilumab treatment, especially the abundance of Staphylococcus aureus. In vitro experiments substantiated the potential role of the microbiome, showing increased growth of A. aceti and decreased growth of S. aureus in presence of dupilumab. Conclusions: Persistent neutrophilic infiltration and a unique microbial landscape on the ocular surface associated with elevated levels of systemic proinflammatory cytokines typify DAOSD. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Abstract Skin metabolites (

Climbing is a fast-growing sport, with one of the most common injuries being a rupture of the finger flexor tendon pulley. The strain on pulleys increases as finger joints flex. However, to our knowledge, no study has conducted a kinematic analysis of climbers’ fingers. Thus, this study aimed to examine finger kinematics during typical climbing tasks. Eleven elite climbers performed a sequence of four climbing moves, which were recorded by an optical motion capture system. Participants used crimp, half-crimp, and open-hand grips for three trials each, with the fourth condition involving campusing using any grip except crimp. Mean proximal interphalangeal joint (PIP) flexion during the holding phase was 87° (SD 12°), 70° (14°) and 39° (27°) for the crimp, half-crimp and open-hand grip, respectively. Hence, inter-individual PIP flexion ranges overlap between different gripping conditions. Two different movement patterns emerged in the open-hand grip, possibly influenced by the use of the little finger, leading to varying degrees of flexion in the middle and ring fingers. Avoiding little finger usage in the open-hand grip may reduce load during pulley rupture rehabilitation. The implications of PIP joint angle variability on individual pulley injury risk or prevention warrant further investigation. Motion capture proved effective for understanding finger kinematics during climbing and could guide future studies on pulley injury risk factors.

Due to the goal of mastering a standardised route with relatively large handholds as quickly as possible, the weighting of performance-determining factors might be different in speed climbing in comparison to lead climbing or bouldering. The objective of this paper was to identify physical and tactical factors for peak performance in speed climbing. Therefore, not only existing literature was reviewed but also a video analysis of the final round of speed climbing at the Olympic games and interviews with experts were done. Out of two hundred and one articles initially found by searching in Medline, Elsevier and Google Scholar databases, 38 were ultimately considered. Generally, an increased lower limb power, a small body mass index, an improved anaerobic glycogen system, and a high fluency in movements were identified as characteristics for high-speed climbing performance. Based on video analysis of Olympic games, coordinated motions, correct foot movements and shorter reaction time could take a novice speed climber to an elite level. Furthermore, male climbers should avoid pairing hands on holds. Considering the increasing popularity, the continued improvement of the record time in this discipline, and the currently limited amount of relevant literature should stimulate future studies on performance-determining variables, assessments, and training methods to maintain the attractiveness of speed climbing.

Despite advances in the understanding of cognitive dysfunction among people with epilepsy (PWE), evidence for cognitive rehabilitation in epilepsy (CoRE) remains scarce. We present the protocol of a randomized waitlist-controlled trial (ClinicalTrials.gov ID NCT05934786) of a psychological-behavioral intervention aiming to ameliorate quality of life as well as cognitive functioning in a mixed PWE sample. The study is set at Vilnius University Hospital Santaros Klinikos and will offer adult PWE six individual and two group sessions led by a certified psychologist and directed toward improving memory, attention, self-regulation, mood and quality of life. The trial is expected to address major gaps in the literature by providing novel evidence on the effectiveness of CoRE in patients with genetic generalized epilepsies, the importance of epilepsy-specific factors for the response to CoRE, the impact of CoRE on long-term memory as well as its maintenance effects.

Abstract Background Exosuits have been shown to reduce metabolic cost of walking and to increase gait performance when used in clinical environment. Currently, these devices are transitioning to private use to facilitate independent training at home and in the community. However, their acceptance in unsupervised settings remains unclear. Therefore, the aim of this study was to investigate end-user perspectives and the adoption of an exosuit in domestic and community settings. Methods We conducted a mixed-method study to investigate the usability and user experience of an exosuit, the Myosuit. We leveraged on a cohort of seven expert users, who had the device available at home for at least 28 days. Each participant completed two standardized questionnaires (SUS and QUEST) and one personalized, custom questionnaire. Furthermore, a semi-structured interview with each participant was recorded, verbatim transcribed and analyzed using descriptive thematic analysis. Data collected from device sensors quantified the frequency of use. Results A mean SUS score of 75.4 out of 100 was reported. Five participants scored above the threshold for above-average usability. Participants also expressed high satisfaction with most of the technical features in the QUEST with an average score of 4.1 (3.86–4.71) out of 5. Participants used the Myosuit mainly for walking outside and exercising at home. However, the frequency of use did not meet the recommendations for physical activity established by the World Health Organization. Five participants used the Myosuit approximately once per week. The two other participants integrated the device in their daily life and used the Myosuit to a greater extent (approx. five times per week). Major factors that prevented an extensive use of the technology were: (i) difficulties in donning that led to (ii) lack of independence and (iii) lack of motivation in exercising. Conclusions Although usable for various activities and well perceived, the adoption of the exosuit in domestic and community settings is yet limited. Use outside the clinic poses further challenges that should be considered when developing new wearable robots. Primarily, design should meet the users' claim for independence and increased adjustability of the device.

Abstract Leukemic cutaneous T‐cell lymphomas (L‐CTCL) are lymphoproliferative disorders of skin‐homing mature T‐cells causing severe symptoms and high mortality through chronic inflammation, tissue destruction, and serious infections. Despite numerous genomic sequencing efforts, recurrent driver mutations have not been identified, but chromosomal losses and gains are frequent and dominant. We integrated genomic landscape analyses with innovative pharmacologic interference studies to identify key vulnerable nodes in L‐CTCL. We detected copy number gains of loci containing the STAT3/5 oncogenes in 74% (n = 17/23) of L‐CTCL, which correlated with the increased clonal T‐cell count in the blood. Dual inhibition of STAT3/5 using small‐molecule degraders and multi‐kinase blockers abolished L‐CTCL cell growth in vitro and ex vivo, whereby PAK kinase inhibition was specifically selective for L‐CTCL patient cells carrying STAT3/5 gains. Importantly, the PAK inhibitor FRAx597 demonstrated encouraging anti‐leukemic activity in vivo by inhibiting tumor growth and disease dissemination in intradermally xenografted mice. We conclude that STAT3/5 and PAK kinase interaction represents a new therapeutic node to be further explored in L‐CTCL.

Objective: Pasireotide is a second-generation somatostatin receptor ligand (SRL) used for treating acromegaly. Its clinical use is limited by adverse effe cts on glucose homeostasis. The aim of this study was to evaluate longitudinal changes in beta-cell function and insulin sensitivity associated with pasireotide in patients not controlled by first-generation SRLs. Design: We performed a retrospective study. Methods: The efficacy (growth hormone (GH)/insulin-like growth factor (IG F-1) concentrations; tumor size) and effect on glucose homeostasis we re analyzed in 33 patients. Longitudinal data on oral glucose tolerance tests were available before, shortly (mean ± s.d., 6.1 ± 3.8 months) and long term (24.4 ± 11.1 months) after initiation of pasireotide in 14 patients. Insulin secretion (insulinogenic index; disposition index) and insulin sensitivity were calculated by validated indices. Results: Pasireotide-induced diabetes occurred in 12 patients (36%). It was mediated by impaired insulin secretion, which occurred shortly after initiation of treatment and then remained stable on long term (insulinogenic index, median (min; max), 80 (12; 542) vs 16 (6.4; 101) vs 25 (3.7; 396) pmol/mmol, respectively; P = 0.028; disposition index, 1.45 (0.42; 4.88) vs 0.53 (0.17; 2.63) vs 0.60 (0.22; 1.71), respectively; P = 0.024). No significant changes in insulin sensitivity were observed, despite a marked reduction of GH/IGF-1 concentrations. Older age and a worse glycemic control at baseline were the strongest predictors for hyperglycemia and the need for antidiabetic treatment. Conclusion: Worsening of glycemic control during pasireotide therapy is caused by an impaired insulin secretion, whereas insulin sensitivity is not affected. These findings might be important for the choice of antidiabetic treatment for pasireotide-induced hyperglycemia. Significance statement: Pasireotide, a second-generation SRL used for treating acromegaly, may be associated with glucose metabolism impairment. In a retrospective study of 33 patients, we observed that treatment with pasireotide was associated with normalization of serum IGF-1 in almost 60% of patients, but one -third of patients developed diabetes. In the patients who stopped pasireotide because of hyperglycemia, HbA1c promptly decreased. Longitudinal data in 14 patients show that diabetes is mediated by impaired insulin secretion, which occurred shortly and then remained stable on long term, while no significant changes in insulin sensitivit y were observed, despite a marked reduction of GH/IGF-1 concentrations. Older age and a wo rse glycemic control at baseline were the strongest predictors for hyperglycemia.

Abstract Objectives To determine the relaxation times of the sodium nucleus, and to investigate the repeatability of quantitative, in vivo TSC measurements using sodium magnetic resonance imaging (23Na-MRI) in human skeletal muscle and explore the discriminatory value of the method by comparing TSCs between healthy subjects and patients with Addison’s disease. Materials and methods In this prospective study, ten healthy subjects and five patients with Addison’s disease were involved. 23Na-MRI data sets were acquired using a density-adapted, three-dimensional radial projection reconstruction pulse sequence (DA-3DPR) with a modification for the relaxation times measurements. Differences in TSC between muscle groups and between healthy participants were analysed using a nonparametric Friedman ANOVA test. An interclass correlation coefficient (ICC) was used as the repeatability index. Wilcoxon rank sum test was used for evaluation of differences in TSC between study participants. Results The mean T1 in the gastrocnemius medialis (GM), the tibialis anterior (TA), and the soleus (S) was 25.9 ± 2.0 ms, 27.6 ± 2.0 ms, and 28.2 ± 2.0 ms, respectively. The mean short component of T2 *, T2 * short were GM: 3.6 ± 2.0 ms; TA: 3.2 ± 0.5 ms; and S: 3.0 ± 1.0 ms, and the mean long component of T2 *, T2 * long, were GM: 12.9 ± 0.9 ms; TA: 12.8 ± 0.7 ms; and S: 12.9 ± 2.0 ms, respectively. In healthy volunteers, TSC values in the GM were 19.9 ±0.1 mmol/L, 13.8 ±0.2 mmol/L in TA, and 12.6 ± 0.2 mmol/L in S, and were significantly different (p = 0.0005). The ICCs for GM, TA and S were 0.784, 0.818, 0.807, respectively. In patients with Addison’s disease, TSC in GC, TA, and S were 10.2 ± 1.0 mmol/L, 8.4 ± 0.6 mmol/L, and 7.2 ± 0.1 mmol/L, respectively. Conclusions TSC quantification in a healthy subject’s calf at 7.0 T is reliable; the technique is able to distinguish sodium level differences between muscles and between healthy subjects and Addison’s disease patients.

Background & Aims: Inadequate adrenal function has been described in patients with cirrhosis. We investigated (i) the pituitary–adrenal axis at different clinical stages and (ii) the clinical impact of decreased serum cortisol levels in stable patients with advanced chronic liver disease (ACLD). Methods: We included 137 outpatients with ACLD undergoing hepatic venous pressure gradient (HVPG) measurement in the prospective VICIS study (NCT03267615). Patients were stratified into six clinical stages: S0: subclinical portal hypertension (PH) (HVPG 6–9 mmHg), S1: clinically significant PH (HVPG ≥10 mmHg) without varices, S2: presence of varices, S3: previous variceal bleeding, S4: previous non-bleeding decompensation, and S5: further decompensation. Results: Fifty-one patients had compensated ACLD (S0: n = 13; S1: n = 12; S2: n = 26), whereas 86 patients had decompensated ACLD (S3: n = 7; S4: n = 46; S5: n = 33). Serum total cortisol (t-Cort) showed a strong correlation with estimated serum free cortisol (f-Cort; Spearman’s ρ: 0.889). With progressive clinical stage, median ACTH levels (from S0: 44.0 pg/ml to S5: 20.0 pg/ml; p = 0.006), t-Cort (from S0: 13.9 μg/dl to S5: 9.2 μg/dl; p = 0.091), and cortisol binding globulin (from S0: 49.3 μg/ml to S5: 38.9 μg/ml; p

Quantifying rowing performance can facilitate control of training load or assessment of skill level. Accordingly, the FlexOmega system was developed, which records the bending moment of the oar. This work aimed to validate this new instrumentation during a dynamic load case. Two force profiles were first derived from bending moments acquired during on-water rowing (one at race pace, one at training pace). These force profiles were then used to repeatedly load the instrumented oar on a newly developed test bench. To ultimately elaborate how precision and accuracy determined on the test bench affects everyday training, i.e., whether practitioners can reasonably use the FlexOmega system, the measurement variability observed on the test bench was related to the measurement variability seen for on-water measurements. On the test bench (featuring a mean precision of 99% and mean accuracy of 95%), a mean error of 3 Nm (mean precision: 98%, mean accuracy: 97%) was determined for the FlexOmega system for the force profile A characterised by bending moments of up to 300 Nm (racing simulated, 37 strokes per minute). For the force profile B with lower stroke rate and less force (21 strokes per minute, up to 150 Nm), the mean error was 2 Nm (mean precision: 98%, mean accuracy: 97%). The measurement variability observed on the test bench was on average for the two force profiles 30% (profile A) and 15% (profile B) of the measurement variability that occurred during on-water rowing. We conclude that improving the measurement characteristics of the instrumentation would hardly result in any practical benefit as on-water measurements seem mainly to be influenced by the rower’s skill level and environmental condition. Thus, the FlexOmega system can be used to control training intensity or to evaluate rowing performance. In addition, the presented approach for elaborating measurement characteristics could contribute to.

Abstract With the introduction of the latest class of biologic drugs targeting interleukin (IL)-23p19, three new, highly effective drugs can be used for the treatment of chronic plaque psoriasis. However, poorer skin improvement as well as higher rates of serious adverse events have been reported for patients under real-world conditions (outside clinical trials). This accounts especially for patients who have already been treated with biologic drugs. We therefore aimed to determine effectiveness and safety of IL-23p19 inhibitors in real-world patients by analysing data from the Psoriasis Registry Austria (PsoRA) in this observational, retrospective, multicentre cohort study. Data for 197 patients (52.3% biologic-non-naïve), who were treated with anti-IL-23p19 antibodies (127 guselkumab, 55 risankizumab and 15 tildrakizumab) for at least 3 months, were eligible for analysis. In general, biologic-non-naïve patients displayed a less favourable response to anti-IL-23 treatment as compared to biologic-naïve patients. However, after correction for previous biologic exposure, few differences in PASI improvement were detected among biologic-naïve and -non-naïve patients treated with different IL-23p19 inhibitors. This indicates that treatment effectiveness is not related to the class of the previously administered therapy in biologic-non-naïve patients. Therefore, IL-23p19 inhibitors represent a promising treatment alternative for patients who have not responded to previous biologics. However, as with other biologic agents (including IL-17 inhibitors), we did not observe an entirely satisfactory treatment response (i.e. PASI < 3 and/or PASI 75) to anti-IL-23 treatment in one out of four to five patients. Adverse events (mainly non-severe infections) were observed in 23 (11.7%) patients with no major differences regarding the administered IL-23 inhibitor or previous biologic exposure.

Abstract Knowledge about the orientation of a representative ankle joint axis is limited to studies of tarsal morphology and of quasistatic movements. The aim of our study was therefore to determine the development of the axis orientation during walking. Intracortical bone pins were used to monitor the kinematics of the talus and tibia of five healthy volunteers. The finite helical axis was determined for moving windows of 10% stance phase and its orientation reported if the rotation about the axis was more than 2°. A representative axis for ankle dorsi- and plantarflexion was also estimated based on tarsal morphology. As reported by literature, the morphology-based axis was inclined more medially upwards for dorsiflexion than for plantarflexion. However, when a mean of the finite helical axis orientations was calculated for each walking trial for dorsiflexion (stance phase 15–25%) and for plantarflexion (stance phase 85–95%), the inclination was less medially upwards in dorsiflexion than in plantarflexion in four out of five participants. Thus, it appears that the inclination of a representative ankle joint axis for dynamic loading situations cannot be estimated from either morphology or quasi-static experiments. Future studies assessing muscle activity, ligament behaviour and articulating surfaces may help to identify the determining factors for the orientation of a representative ankle joint axis.

Narrowband-ultraviolet B has shown increased efficacy over broadband-ultraviolet B in pruritic skin diseases, such as psoriasis and atopic dermatitis. In patients with chronic pruritus, e.g. in end-stage renal disease, broadband-ultraviolet B is recommended, but narrowband-ultraviolet B has also shown efficacy in reducing pruritus. This randomized, single blinded, non-inferiority study investigated the effects of narrowband-ultraviolet B compared with broadband-ultraviolet B. Patients with chronic pruritus were treated with either broadband- or narrowband-UVB 3 times a week for 6 weeks and clinical response was monitored. Pruritus, sleep disturbance, and the patients’ subjective overall response to treatment were evaluated by the patients on a visual analogue scale (0–10). Skin excoriations were evaluated by investigators on a 4-point scale (0–3). Both phototherapeutic modalities showed significant antipruritic activity (itch reduction 48% and 66.4%, respectively) by broadband-ultraviolet B and narrowband-ultraviolet B. Narrowband-ultraviolet B proved to be not inferior to broadband-ultraviolet B in treating pruritus in patients with chronic pruritus, assuming a 20% non-inferiority margin.

A 24-year-old man with diabetes mellitus presented with advanced kidney disease and severe proteinuria. Genetic testing revealed ABCC8-MODY12 (OMIM 600509), and a kidney biopsy showed nodular glomerulosclerosis. He commenced dialysis shortly thereafter, and glycemic control improved on treatment with a sulfonylurea. Diabetic end-stage kidney disease in patients with ABCC8-MODY12 has not been reported until now. Thus, our case highlights the risk for early-onset and severe diabetic kidney disease in patients with ABCC8-MODY12 and the importance of timely genetic diagnosis in unusual cases of diabetes to allow for proper treatment and prevention of late sequelae of diabetes.

Over the past decades, adapted lifestyle and dietary habits in industrialized countries have led to a progress of obesity and associated metabolic disorders. Concomitant insulin resistance and derangements in lipid metabolism foster the deposition of excess lipids in organs and tissues with limited capacity of physiologic lipid storage. In organs pivotal for systemic metabolic homeostasis, this ectopic lipid content disturbs metabolic action, thereby promotes the progression of metabolic disease, and inherits a risk for cardiometabolic complications. Pituitary hormone syndromes are commonly associated with metabolic diseases. However, the impact on subcutaneous, visceral, and ectopic fat stores between disorders and their underlying hormonal axes is rather different, and the underlying pathophysiological pathways remain largely unknown. Pituitary disorders might influence ectopic lipid deposition indirectly by modulating lipid metabolism and insulin sensitivity, but also directly by organ specific hormonal effects on energy metabolism. In this review, we aim to I) provide information about the impact of pituitary disorders on ectopic fat stores, II) and to present up-to-date knowledge on potential pathophysiological mechanisms of hormone action in ectopic lipid metabolism.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease that significantly affects the patient’s quality of life. A disrupted skin barrier, type 2 cytokine-dominated inflammation, and microbial dysbiosis with increased Staphylococcus aureus colonization are critical components of AD pathogenesis. Patients with AD exhibit decreased expression of antimicrobial peptides (AMPs) which is linked to increased colonization by Staphylococcus aureus. The skin microbiome itself is a source of several AMPs. These host- and microbiome-derived AMPs define the microbial landscape of the skin based on their differential antimicrobial activity against a range of skin microbes or their quorum sensing inhibitory properties. These are particularly important in preventing and limiting dysbiotic colonization with Staphylococcus aureus. In addition, AMPs are critical for immune homeostasis. In this article, we share our perspectives about the implications of microbial derived AMPs in AD patients and their potential effects on overlapping factors involved in AD. We argue and discuss the potential of bacterial AMPs as therapeutics in AD.

Abstract Background Wearable robots have been shown to improve the efficiency of walking in diverse scenarios. However, it is unclear how much practice is needed to fully adapt to robotic assistance, and which neuromotor processes underly this adaptation. Familiarization strategies for novice users, robotic optimization techniques (e.g. human-in-the-loop), and meaningful comparative assessments depend on this understanding. Methods To better understand the process of motor adaptation to robotic assistance, we analyzed the energy expenditure, gait kinematics, stride times, and muscle activities of eight naïve unimpaired participants across three 20-min sessions of robot-assisted walking. Experimental outcomes were analyzed with linear mixed effect models and statistical parametric mapping techniques. Results Most of the participants’ kinematic and muscular adaptation occurred within the first minute of assisted walking. After ten minutes, or 880 steps, the energetic benefits of assistance were realized (an average of 5.1% (SD 2.4%) reduction in energy expenditure compared to unassisted walking). Motor adaptation was likely driven by the formation of an internal model for feedforward motor control as evidenced by the reduction of burst-like muscle activity at the cyclic end of robotic assistance and an increase in arm-swing asymmetry previously associated with increased cognitive load. Conclusion Humans appear to adapt to walking assistance from a wearable robot over 880 steps by forming an internal model for feedforward control. The observed adaptation to the wearable robot is well-described by existing three-stage models that start from a cognitive stage, continue with an associative stage, and end in autonomous task execution. Trial registration Not applicable.

Objective: Measurement of IGF-I is important in the management of patients with growth hormone disorders. Here we aim to establish normative data for two new IGF-I assay kits based on a large random sample of the French general adult population. Subjects and methods: We measured IGF-I in 911 healthy adults (18–90 years) with two immunoassays (ROCHE Elecsys® and IMMULITE-2000 calibrated against the new IS 02/2547). We compared the data with those of the six immunoassays (iSYS, LIAISON XL, IMMULITE-2000 calibrated against the first IS 87/518, IGF-I RIAC T, Mediagnost ELISA, and Mediagnost RIA) that we reported previously. The pairwise concordance among the eight assays was assessed with Bland–Altman plots for both the IGF-1 raw data and the standard deviation scores (SDS), as well as with the percentage of observed agreement and the weighted Kappa coefficient for categorizing IGF-I SDS (ClinicalTrials.gov Identifier: NCT01831648). Results: The normative data included the range of values (2.5–97.5 percentiles) given by the two new IGF-I assays according to age group and sex. A formula for the SDS calculation is provided. As for the previous six assays, the lower limits of the reference intervals of the two new assays were similar, but the upper limits varied markedly. The pairwise concordances were only moderate (kappa 0.57). Conclusions: Data obtained for these two new IGF-I immunoassays confirm that despite being obtained in the same large healthy population, the reference intervals of the eight commercial IGF-1 assay kits showed noteworthy differences. The a greement among the various methods was moderate to good.

Abstract Background Scapular dyskinesis, i.e., the deviant mobility or function of the scapula, hampers upper limb function in daily life. A typical sign of scapular dyskinesis is a scapula alata—a protrusion of the shoulder blade during arm elevation. While some reversible causes of scapula alata can be treated with therapy, other, irreversible causes require invasive surgical interventions. When surgery is not an option, however, severe limitations arise as standard approaches for assisting the scapula in daily life do not exist. The aim of this study was to quantify functional improvements when external, i.e., non-invasive, scapula assistance is provided. Methods The study was designed as a randomized controlled crossover trial. Eight participants with a scapula alata due to muscular dystrophy performed arm elevations in shoulder flexion and abduction while unassisted (baseline), externally assisted by a trained therapist, and externally assisted by a novel, textile-based scapula orthosis. Results With therapist assistance, average arm elevation increased by 17.3° in flexion (p

Abstract Most wearable robots that assist the gait of workers, soldiers, athletes, and hobbyists are developed towards a vision of outdoor, overground walking. However, so far, these devices have predominantly been tested indoors on laboratory treadmills. It is unclear whether treadmill-based laboratory tests are an accurate representation of overground ambulation outdoors with respect to essential outcomes such as the metabolic benefits of robotic assistance. In this study, we investigated the metabolic benefits of the Myosuit, a wearable robot that assists hip and knee extension during the stance phase of gait, for eight unimpaired participants during uphill walking trials in three settings: outside, on a self-paced treadmill with a virtual reality display, and on a standard treadmill at a fixed gait speed. The relative metabolic reduction with Myosuit assistance was most pronounced in the outside setting at − 10.6% and significantly larger than in the two treadmill settings (− 6.9%, p = 0.015 and − 6.2%, p = 0.008). This indicates that treadmill tests likely result in systematically low estimate for the true metabolic benefits of wearable robots during outside, overground walking. Hence, wearable robots should preferably be tested in an outdoor environment to obtain more representative—and ultimately more favorable—results with respect to the metabolic benefit of robotic gait assistance.

Most robotic gait assisted devices are designed to provide constant assistance during the training without taking into account each patient’s functional ability. The Lokomat offers an assist-as-needed control via the integrated exercise “Adaptive Gait Support” (AGS), which adapts the robotic support based on the patient’s abilities. The aims of this study were to examine the feasibility and characteristics of the AGS during long-term application. Ten patients suffering from neurological diseases underwent an 8-week Lokomat training with the AGS. They additionally performed conventional walking tests and a robotic force measurement. The difference between robotic support during adaptive and conventional training and the relationship between the robotic assessment and the conventional walking and force tests were examined. The results show that AGS is feasible during long-term application in a heterogeneous population. The support during AGS training in most of the gait phases was significantly lower than during conventional Lokomat training. A relationship between the robotic support level determined by the AGS and conventional walking tests was revealed. Moreover, combining the isometric force data and AGS data could divide patients into clusters, based on their ability to generate high forces and their level of motor control. AGS shows a high potential in assessing patients’ walking ability, as well as in providing challenging training, e.g., by automatically adjusting the robotic support throughout the whole gait cycle and enabling training at lower robotic support.

Background: Little is known about the effectiveness and drug survival associated with apremilast under real-world conditions. Objective: To investigate the influence of patient and disease characteristics on drug survival associated with apremilast and to elucidate clinical effectiveness with regard to the psoriasis area and severity index (PASI) reduction. Methods: This was an observational, retrospective, multicenter analysis from the Austrian Psoriasis Registry. Results: Data from 367 patients were eligible for analysis. The 12-month drug survival rate associated with apremilast (ie, the proportion of patients on the drug) was 57.3% and decreased significantly in patients younger than 40 years (relative hazard ratio = 1.49, P = .007918). Sex; concomitant arthritis; previous biologic therapy; obesity; and palmoplantar, scalp, nail, and intertriginous involvement did not significantly affect drug survival. At 12 months, the response rates in patients receiving apremilast per protocol with a PASI of 50, 75, 90, and 100 were 80.0%, 56.4%, 38.2%, and 22.7%, respectively. Limitations: Inclusion of a substantial number of patients with no record of absolute PASI at study entry and lack of PASI reduction follow-up data of 103 patients (28.1%) after starting apremilast treatment. Conclusion: Apremilast is a robust antipsoriatic drug for which the drug survival is not strongly influenced by most patient- or disease-related factors except age. Drug survival is significantly shorter in patients younger than 40 years.

Atomic clocks and their networks are useful tools for optical communications and frequency metrology. Here the authors use phase stabilization and active tip-tilt to suppress atmospheric effects and enable optical frequency transfer through free-space.

Patients with polymorphic light eruption (PLE) develop lesions upon the first exposure to sun in spring/summer, but lesions usually subside during season due to the natural (or medical) photohardening. However, these lesions tend to reappear the following year and continue to do so in most patients, suggesting the presence of a disease memory. To study the potential role of skin resident memory T cells (Trm), we investigated the functional phenotype of Trm and the expression of IL-15 in PLE. IL-15 is known to drive Trm proliferation and survival. Multiplex immunofluorescence was used to quantify the expression of CD3, CD4, CD8, CD69, CD103, CD49a, CD11b, CD11c, CD68, granzyme B (GzmB), interferon-gamma (IFN-γ), and IL-15 in formalin-fixed, paraffin-embedded lesional skin samples from PLE patients and healthy skin from control subjects. Unlike the constitutive T cell population in healthy skin, a massive infiltration of T cells in the dermis and epidermis was observed in PLE, and the majority of these belonged to CD8+ T cells which express Trm markers (CD69, CD103, CD49a) and produced cytotoxic effector molecules GzmB and IFN-γ. Higher numbers of CD3+ T cells and CD11b+CD68+ macrophages produced IL-15 in the dermis as compared to healthy skin. The dominant accumulation of cytotoxic Trm cells and increased expression of IL-15 in lesional skin of PLE patients strongly indicates the potential role of skin Trm cells in the disease manifestation and recurrence.

Abstract Background Physical activity is a recommended part of treatment for numerous neurological and neuromuscular disorders. Yet, many individuals with limited mobility are not able to meet the recommended activity levels. Lightweight, wearable robots like the Myosuit promise to facilitate functional ambulation and thereby physical activity. However, there is limited evidence of the safety and feasibility of training with such devices. Methods Twelve participants with diverse motor disorders and the ability to walk for at least 10 m were enrolled in this uncontrolled case series study. The study protocol included five training sessions with a net training time of 45 min each. Primary outcomes were the feasibility of engaging in training with the Myosuit, the occurrence of adverse events, and participant retention. As secondary outcomes, we analyzed the walking speed using the 10-m Walk Test (10MWT) and for three participants, walking endurance using the 2-min Walk Tests. Results Eight out of 12 participants completed the entire study protocol. Three participants withdrew from the study or were excluded for reasons unrelated to the study. One participant withdrew because of an unsafe feeling when walking with the Myosuit. No adverse events occurred during the study period for any of the participants and all scheduled trainings were completed. For five out of the eight participants that completed the full study, the walking speed when using the Myosuit was higher than to their baseline walking speed. Conclusions Activity-based training with the Myosuit appears to be safe, feasible, and well-tolerated by individuals with diverse motor disorders.

A variety of non-filtering agents have been introduced to enhance sunscreen photoprotection. Most of those agents have only weak erythema protective properties but may be valuable and beneficial in supporting protection against other effects of UV radiation, such as photoimmunosuppression, skin aging, and carcinogenesis, as well as photodermatoses. The question arises how to measure and evaluate this efficacy since standard SPF testing is not appropriate. In this perspective, we aim to provide a position statement regarding the actual value of SPF and UVA-PF to measure photoprotection. We argue whether new or additional parameters and scales can be used to better indicate the protection conferred by these products against the detrimental effects of natural/artificial, UV/visible light beyond sunburn, including DNA damage, photoimmunosuppression and pigmentation, and the potential benefits of the addition of other ingredients beyond traditional inorganic and organic filters to existing sunscreens. Also, we debate the overall usefulness of adding novel parameters that measure photoprotection to reach two tiers of users, that is, the general public and the medical community; and how this can be communicated to convey the presence of additional beneficial effects deriving from non-filtering agents, e.g., biological extracts. Finally, we provide a perspective on new challenges stemming from environmental factors, focusing on the role of the skin microbiome and the role of air pollutants and resulting needs for photoprotection.

Assistive forces transmitted from wearable robots to the robot’s users are often defined by controllers that rely on the accurate estimation of the human posture. The compliant nature of the human–robot interface can negatively affect the robot’s ability to estimate the posture. In this article, we present a novel algorithm that uses machine learning to correct these errors in posture estimation. For that, we recorded motion capture data and robot performance data from a group of participants (n = 8; 4 females) who walked on a treadmill while wearing a wearable robot, the Myosuit. Participants walked on level ground at various gait speeds and levels of support from the Myosuit. We used optical motion capture data to measure the relative displacement between the person and the Myosuit. We then combined this data with data derived from the robot to train a model, using a grading boosting algorithm (XGBoost), that corrected for the mechanical compliance errors in posture estimation. For the Myosuit controller, we were particularly interested in the angle of the thigh segment. Using our algorithm, the estimated thigh segment’s angle RMS error was reduced from 6.3° (2.3°) to 2.5° (1.0°), mean (standard deviation). The average maximum error was reduced from 13.1° (4.9°) to 5.9° (2.1°). These improvements in posture estimation were observed for all of the considered assistance force levels and walking speeds. This suggests that ML-based algorithms provide a promising opportunity to be used in combination with wearable-robot sensors for an accurate user posture estimation.

Background and objective Hyponatremia and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) are associated with and can be caused by tuberculosis (TB) through meningitis by locally invading the hypothalamus, adrenal, or pituitary glands or possibly through ectopic ADH production. This study assessed the association of TB mortality with hyponatremia and SIADH in a large cohort of a university hospital in Austria. Methods This retrospective study enrolled patients with hyponatremia and patients diagnosed with TB from 01/2001-11/2019 to assess the prevalence of TB in hyponatremia and TB morbidity and mortality in patients with and without hyponatremia. Sex, age, microbiological results, laboratory tests and comorbidities were analysed and used to calculate survival rates. Results Of 107.532 patients with hyponatremia (0.07%) and 186 patients with TB (43%), 80 patients were diagnosed with both—hyponatremia and TB. Only three TB patients had SIADH, precluding further SIADH analysis. In hyponatremia, young age and high CRP levels showed significant associations with TB diagnosis (pConclusion In this study of a large cohort from a tertiary care hospital in a non-endemic area of TB, 0.07% of patients presenting with hyponatremia, but especially younger patients and patients with high CRP values, were diagnosed with TB. Crucially, patients with moderate to profound hyponatremia had a significantly higher mortality rate and thus required increased medical care.

Background: Little is known about the long-term course of polymorphic light eruption (PLE).Objective: To predict disease course, a questionnaire was sent to patients whose PLE had been diagnosed between March 1990 and December 2018 and documented in the Austrian Cooperative Registry for Photodermatoses.Methods: In January 2019, 205 PLE patients were contacted by mail and asked to complete a questionnaire on their disease course, including whether the skin's sun sensitivity had normalized (i.e., PLE symptoms had disappeared), improved, stayed the same, or worsened over time. Patients who reported normalization of sun sensitivity were asked to report when it had occurred.Results: Ninety-seven patients (79 females, 18 males) returned a completed questionnaire. The mean (range) duration of follow-up from PLE onset was 29.6 (17–54) years for females and 29.4 (16–47) years for males. The disease disappeared in 32 (41%) females after 17.4 (2–41) years and in 4 (24%) males after 11.8 (5–26) years. Twenty-nine (37%) females and 6 (35%) males reported improvement of symptoms over time; 15 females (19%) and 7 males (41%) reported no change; and 3 females (4%) and no males reported worsening of symptoms. Kaplan-Meier analysis revealed that after 20 years 74% (95%CI, 64–82%) of patients still suffered from PLE. PLE lesion persistence (>1 week) tended to predict a prolonged course of PLE.Conclusions: PLE usually takes a long-term course over many years though in most patients its symptoms improve or disappear over time. How improvement relates to the pathophysiology of the disease remains to be determined.

Abstract Particle dark matter could have a mass anywhere from that of ultralight candidates, m χ ∼ 10−21 eV, to scales well above the GeV. Conventional laboratory searches are sensitive to a range of masses close to the weak scale, while new techniques are required to explore candidates outside this realm. In particular lighter candidates are difficult to detect due to their small momentum. Here we study two experimental set-ups which do not require transfer of momentum to detect dark matter: atomic clocks and co-magnetometers. These experiments probe dark matter that couples to the spin of matter via the very precise measurement of the energy difference between atomic states of different angular momenta. This coupling is possible (even natural) in most dark matter models, and we translate the current experimental sensitivity into implications for different dark matter models. It is found that the constraints from current atomic clocks and co-magnetometers can be competitive in the mass range m χ ∼ 10−21−103 eV, depending on the model. We also comment on the (negligible) effect of different astrophysical neutrino backgrounds.

Summary: The skin is colonized by a diverse microbiome intricately involved in various molecular and cellular processes within the skin and beyond. UV radiation is known to induce profound changes in the skin and modulate the immune response. However, the role of the microbiome in UV-induced immune suppression has been overlooked. By employing the standard model of contact hypersensitivity (using germ-free mice) we found diminished UV-induced systemic immune suppression in the presence of microbiome. Upon UV exposure, we found enhanced epidermal hyperplasia and neutrophilic infiltration in the presence and enhanced numbers of mast cells and monocyte or macrophages in the absence of microbiome. Transcriptome analysis revealed a predominant expression of cytokine genes related to pro-inflammatory milieu in the presence versus immunosuppressive milieu (with increased interleukin-10) in the absence of microbiome. Collectively, microbiome abrogates the immunosuppressive response to UV by modulating gene expression and cellular microenvironment of the skin. : Dermatology; Radiation Biology; Immune Response; Microbiome Subject Areas: Dermatology, Radiation Biology, Immune Response, Microbiome

Background: Migraine and epilepsy are both common episodic disorders, typically precipitated or inhibited by some modulatory factors (MFs).Objective: To assess the self-perception of MFs in patients with migraine (PWM) compared to patients with epilepsy (PWE) with a standardized protocol in different countries.Methods: Transcultural multicenter comparative cross-sectional study. All consecutive patients who fulfilled the ICHD-3 criteria for migraine and ILAE's criteria for epilepsy, with at least 1 year of follow-up were interviewed with a semi-structured questionnaire on clinical and epidemiological data and were asked to identify all experienced MFs from a provided list.Results: A total of 608 individuals were surveyed at five university referral centers in Brazil, Guatemala, Lithuania and Turkey. Two hundred and nineteen (91.6%) PWM and 305 (82.7%) PWE identified attack precipitating factors (PFs; p < 0.001). The most frequent three PFs reported by epilepsy patients were: “lack of sleep” (56.6%), “emotional stress” (55.3%), “negative feelings” (53.9%), while among migraine patients “emotional stress” (81.6%), “lack of sleep” (77.8%), “negative feelings” (75.7%) were cited. Inhibitory factors (IFs) for the episodes were reported by 68 (28.5%) PWM and 116 (31.4%) PWE. “Darkness” was the most common one, described by 35.6% of PWM whereas “positive feelings” reported by 10.6% of PWE. Most MFs are concordant across the countries but some transcultural differences were noted.Conclusion: The MFs of migraine and epilepsy attacks and their varying frequencies according to different countries were investigated with the same standardized questionnaire, for the first time. MFs were recognized very often in both migraine and epilepsy cohorts, but in distinct disease-specific prevalence, being more frequent in migraine. Recognition of self-perceived MFs may be helpful for the management of both illnesses.

Pituitary hormone axes modulate glucose metabolism and exert direct or indirect effects on insulin secretion and function. Cortisol and growth hormone are potent insulin-antagonistic hormones. Therefore impaired glucose tolerance, elevated fasting glucose concentrations and diabetes mellitus are frequent in Cushing’s disease and acromegaly. Also prolactinomas, growth hormone (GH) deficiency, hypogonadism and hypothyroidism might be associated with impaired glucose homeostasis but usually to a lesser extent. Therefore glucose metabolism needs to be closely monitored and treated in patients with pituitary adenomas. Correction of the pituitary dysfunction is frequently followed by improvement of glucose homeostasis.

Background: SARS-Cov2 has raised concerns among dermatologists regarding psoriasis and its respective treatments. Comorbidities, which induce the expression of the proprotease furin have been associated with severe course of COVID-19. Furin and angiotensin converting enzyme 2 (ACE2) play a major role in viral host cell entry of SARS-Cov2.Objective: To evaluate mRNA expression of Furin and ACE2 from blood cells in psoriasis patients, and whether systemic or topical treatment reduces expression levels.Methods: This observational translational study analyzed blood samples from patients from a clinical trial and samples retrieved from the biobank of the Psoriasis Registry Austria (PsoRA). Furin and ACE2 expression levels were analyzed prior to as well as 3 and 12–24 months after start of biologic treatment with either ustekinumab or secukinumab. Additionally, the study analyzed expression levels prior to, 6 days after start of dithranol treatment and 4–6 weeks after end of dithranol treatment.Results: Furin mRNA expression was significantly increased at baseline in the biologic (4.9 ± 2.6 fold, p < 0.0001) and in the dithranol group (2.7 ± 1.4 fold, p < 0.001) compared to controls. There was a trend for arthritis patients to express more furin than patients with psoriatic skin involvement only (5.26 ± 2.30 vs. 3.48 ± 2.27, p = 0.078). Analyzing furin mRNA expression after treatment initiation with secukinumab or ustekinumab revealed a normalization of levels after 3 and 12 to 24 months. Similar findings were obtained for patients treated with dithranol, with significantly decreased expression levels 6 days after start of dithranol treatment and also at follow-up, (4–6 weeks after dithranol treatment had been terminated). ACE2 expression levels did not differ from controls at any timepoint, regardless of biologic or topical treatment.Conclusion: Significantly overexpressed levels of furin were observed in untreated patients, and, thus, these patients may be at risk for infection and a severe course of COVID-19. However, the data indicate that successful therapeutic intervention in psoriasis, by systemic biologic or topical treatment, can efficiently reduce furin levels in blood cells, possibly limiting the risk of psoriasis patients for a severe COVID-19 course.Clinical Trial Registration:ClinicalTrials.gov, identifier NCT02752672.

Background: This study assessed the predictive performance of inflammatory, hepatic, coagulation, and cardiac biomarkers in patients with prediabetes and diabetes mellitus hospitalized for COVID-19 in Austria. Methods: This was an analysis of a multicenter cohort study of 747 patients with diabetes mellitus or prediabetes hospitalized for COVID-19 in 11 hospitals in Austria. The primary outcome of this study was in-hospital mortality. The predictor variables included demographic characteristics, clinical parameters, comorbidities, use of medication, disease severity, and laboratory measurements of biomarkers. The association between biomarkers and in-hospital mortality was assessed using simple and multiple logistic regression analyses. The predictive performance of biomarkers was assessed using discrimination and calibration. Results: In our analysis, 70.8% had type 2 diabetes mellitus, 5.8% had type 1 diabetes mellitus, 14.9% had prediabetes, and 8.6% had other types of diabetes mellitus. The mean age was 70.3 ± 13.3 years, and 69.3% of patients were men. A total of 19.0% of patients died in the hospital. In multiple logistic regression analysis, LDH, CRP, IL-6, PCT, AST-ALT ratio, NT-proBNP, and Troponin T were significantly associated with in-hospital mortality. The discrimination of NT-proBNP was 74%, and that of Troponin T was 81%. The calibration of NT-proBNP was adequate (p = 0.302), while it was inadequate for Troponin T (p = 0.010). Conclusion: Troponin T showed excellent predictive performance, while NT-proBNP showed good predictive performance for assessing in-hospital mortality in patients with diabetes mellitus hospitalized with COVID-19. Therefore, these cardiac biomarkers may be used for prognostication of COVID-19 patients.