Cholesterol uptake in the intestine is regulated by the LASP1-AKT-NPC1L1 signaling pathway.

Cholesterol is essential for the stability and architecture of the plasma membrane and a precursor of bile acids and steroid hormones in mammals. Excess dietary cholesterol uptake leads to hypercholesterolaemia, atherosclerosis and plays a role in cancer development. The role of actin-binding scaffolding protein LIM and SH3 protein 1 (LASP1) in cholesterol trafficking has not been investigated previously. Cholesterol levels, its uptake and excretion were studied in mice deficient for low density lipoprotein receptor and Lasp1 (Ldlr-/-Lasp1-/- mice) upon feeding a high fat diet, and in LASP1-knockdown, differentiated human intestinal epithelial Caco-2 cells. Compared to diet-fed Ldlr-/- control mice, Ldlr-/-Lasp1-/- mice displayed a reduction in serum cholesterol levels. Mechanistically, we identified a new role of LASP1 in controlling the translocation of the intestinal cholesterol transporter Niemann-Pick C1-like 1 (NPC1L1) to the apical cell surface, which was limited in LASP1-knockdwon human CaCo-2 enterocytes and in the intestine of Ldlr-/- Lasp1-/- compared to Ldlr-/-mice, linked to LASP1-pAKT signaling but not CDC42 activation. In line, a reduction in cholesterol reabsorption was noted in LASP1-knockdown CaCo-2 cells in vitro, and an enhanced cholesterol excretion via the feces was observed in Ldlr-/- Lasp1-/- mice. These data uncover a novel function of Lasp1 in cholesterol trafficking, promoting cholesterol reabsorption in the intestine. Targeting LASP1 locally could thus represent a novel targeting strategy to ameliorate hypercholesterolemia and associated diseases.

Sources of Social Support and Trauma Recovery: Evidence for Bidirectional Associations from a Recently Trauma-Exposed Community Sample.

Although the association between post-traumatic stress disorder (PTSD) and social support is well documented, few studies have tested the causal pathways explaining this association at several points in the acute post-trauma recovery period or examined whether the association varies for different sources of social support. To address these gaps, 151 community individuals (mean age = 37.20 years, 69.5% women) exposed to trauma within the previous 6 months were recruited to complete measures of PTSD and social support from intimate partners, friends, and relatives four times in 1 year. In line with recent recommendations for research on social support and PTSD symptoms, random intercept cross-lagged panel modeling (RI-CLPM) was used to examine dynamic changes between PTSD severity and social support over time. The pattern of RI-CLPM cross-lagged coefficients indicated that positive deviations from one's expected stable level of total social support (across all sources) sped up the recovery of PTSD symptoms at the end of the post-trauma year, and more severe PTSD symptoms than expected based on one's expected stable level of PTSD started eroding social support midway through the assessment year. When specific sources of social support were analyzed separately, the association between within-person increases in social support from friends at any given time point accelerated the recovery from PTSD across the entire year. Among participants with intimate partners (n = 53), intimate partner support did not predict PTSD symptoms, but more severe PTSD symptoms at any given time point predicted less support at the following time point. Results from this longitudinal study provide additional support for the bidirectional relationship between PTSD and social support over time and suggest that perceived social support from friends may be especially helpful during trauma recovery.

Digital interventions to promote psychological resilience: a systematic review and meta-analysis.

Societies are exposed to major challenges at an increasing pace. This underscores the need for preventive measures such as resilience promotion that should be available in time and without access barriers. Our systematic review summarizes evidence on digital resilience interventions, which have the potential to meet these demands. We searched five databases for randomized-controlled trials in non-clinical adult populations. Primary outcomes were mental distress, positive mental health, and resilience factors. Multilevel meta-analyses were performed to compare intervention and control groups at post-intervention and follow-up assessments. We identified 101 studies comprising 20,010 participants. Meta-analyses showed small favorable effects on mental distress, SMD = -0.24, 95% CI [-0.31, -0.18], positive mental health, SMD = 0.27, 95% CI [0.13, 0.40], and resilience factors, SMD = 0.31, 95% CI [0.21, 0.41]. Among middle-aged samples, older age was associated with more beneficial effects at follow-up, and effects were smaller for active control groups. Effects were comparable to those of face-to-face interventions and underline the potential of digital resilience interventions to prepare for future challenges.

The interplay between music engagement and affect: A random-intercept cross-lagged panel analysis.

Engagement with music has the capacity to influence and be influenced by affective experiences. Although cross-sectional and experimental research provides evidence that music engagement is related to higher positive and lower negative affect, few studies have investigated the bidirectional nature of this relationship over time. The present longitudinal study, therefore, examined the interplay between passive and active music engagement and affect using random-intercept cross-lagged panel analysis. Over 8 weeks in 2022, 428 participants regularly engaging with music completed weekly online surveys on quantitative music engagement (i.e., time spent with music listening/music making), qualitative music engagement (i.e., use of music listening/music making for mood regulation) as well as positive and negative affect. Results revealed cross-lagged associations between music engagement and negative affect, but not positive affect: regarding quantitative music engagement, more time spent with music listening (but not music making) was related to less negative affect than usual at the following measurement. Results on qualitative music engagement showed that weeks with more negative affect than usual were followed by an increased use of music listening and music making for mood regulation. Our findings emphasize the bidirectional nature of the relationship between music engagement and affect corroborating the significant role of music engagement in affect regulation. Future research should replicate these findings with a more diverse sample regarding age, sex, ethnicity, education, and socioeconomic status. Additionally, further studies could examine individual and contextual factors and adequate measurement time points for further investigation of bidirectional affective processes involved in music engagement. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cognitive reappraisal in mHealth interventions to foster mental health in adults: a systematic review and meta-analysis.

Background: An increasing number of mHealth interventions aim to contribute to mental healthcare of which interventions that foster cognitive reappraisal may be particularly effective. Objectives: To evaluate the efficacy of mHealth interventions enhancing cognitive reappraisal to improve mental health in adult populations. Methods: The literature search (four databases) yielded 30 eligible randomized controlled trials (comprising 3,904 participants). We performed a multi-level meta-analysis to examine differences between intervention and comparator conditions at post-intervention assessment. Moderator analyses were conducted for potential moderator variables (e.g., type of comparators). Results: Most interventions were CBT-based with other training components in addition to cognitive reappraisal. We found preliminary evidence for a small to medium effect favouring mHealth interventions to enhance cognitive reappraisal over comparators, M(SMD) = 0.34, p = .002. When analysing single symptoms, there was evidence for a small to medium effect of mHealth interventions on anxiety and depressive symptoms, but not for psychological distress and well-being. All analyses showed substantial heterogeneity. Moderator analyses revealed evidence for more favourable effects in studies with passive comparators. There was an overall high risk of bias in most of the studies. Conclusions: We found preliminary evidence for a small to medium effect of mHealth interventions including a cognitive reappraisal component to improve mental health. However, most of the interventions were complex (i.e., reappraisal was provided alongside other components), which prevents us from examining reappraisal-specific effects beyond general mental health promotion in mHealth. Dismantling studies examining the effects of single intervention components are warranted to corroborate these promising results. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=142149, identifier [CRD42019142149].

Interrelations of resilience factors and their incremental impact for mental health: insights from network modeling using a prospective study across seven timepoints.

Resilience can be viewed as trajectory of stable good mental health or the quick recovery of mental health during or after stressor exposure. Resilience factors (RFs) are psychological resources that buffer the potentially negative effects of stress on mental health. A problem of resilience research is the large number of conceptually overlapping RFs complicating their understanding. The current study sheds light on the interrelations of RFs in the face of the COVID-19 pandemic as a use case for major disruptions. The non-preregistered prospective study assessed a sample of 1275 German-speaking people from February 2020 to March 2021 at seven timepoints. We measured coping, hardiness, control beliefs, optimism, self-efficacy, sense of coherence (SOC), sense of mastery, social support and dispositional resilience as RFs in February 2020, and mental health (i.e., psychopathological symptoms, COVID-19-related rumination, stress-related growth) at all timepoints. Analyses used partial correlation network models and latent growth mixture modeling (LGMM). Pre-pandemic RFs were strongly interrelated, with SOC being the most central node. The strongest associations emerged between coping using emotional support and social support, SOC and sense of mastery, and dispositional resilience and self-efficacy. SOC and active coping were negatively linked. When we examined RFs as predictors of mental health trajectories, SOC was the strongest predictor of psychopathological symptoms and rumination, while trajectories of stress-related growth were predicted by optimism. Subsequent network analyses, including individual intercepts and slopes from LGMM, showed that RFs had small to moderate associations with intercepts but were unrelated to slopes. Our findings provide evidence for SOC playing an important role in mental distress and suggest further examining SOC's incremental validity. However, our results also propose that RFs might be more important for stable levels of mental health than for adaptation processes over time. The differential associations for negative and positive outcomes support the use of multidimensional outcomes in resilience research.

Generation climate crisis, COVID-19, and Russia-Ukraine-War: global crises and mental health in adolescents.

Climate change, COVID-19, and the Russia-Ukraine War are some of the great challenges of our time. These global crises affect young people in a particularly vulnerable phase of their lives. The current study aimed to assess the impact of these crises on mental health (depression, anxiety, and health-related quality of life) in secondary school students in Germany. Furthermore, we assessed known predictors of mental health, such as socio-economic factors, individual life stressors, and resilience factors (self-efficacy, expressive flexibility) as covariates. In our sample of 3998 pupils, pandemic- and climate-related distress were linked to greater depression and anxiety and reduced health-related quality of life. War-related distress was associated with greater anxiety. Critically, these associations remained significant after controlling for all covariates, supporting the incremental predictive value of the crises measures. The study reveals a significant impact of the crises on the mental health of the current generation of adolescents. As such it suggests that mental health policies should include interventions that help youth to cope with the stress caused by the crises.

World Health Organization's low-intensity psychosocial interventions: a systematic review and meta-analysis of the effects of Problem Management Plus and Step-by-Step.

Many societies have been recently exposed to humanitarian and health emergencies, which have resulted in a large number of people experiencing significant distress and being at risk to develop mental disorders such as depression, anxiety and post-traumatic stress disorder. The World Health Organization has released a series of scalable psychosocial interventions for people impaired by distress in communities exposed to adversities. Prominent among these is a low-intensity transdiagnostic psychosocial intervention, Problem Management Plus (PM+), and its digital adaptation Step-by-Step (SbS). This systematic review is the first to summarize the available evidence on the effects of PM+ and SbS. Up to March 8, 2023, five databases were searched for randomized controlled trials examining the effects of PM+ or SbS on distress indicators (i.e., general distress; anxiety, depressive or post-traumatic stress disorder symptoms; functional impairment, self-identified problems) and positive mental health outcomes (i.e., well-being, quality of life, social support/relationships). We performed random-effects multilevel meta-analyses on standardized mean differences (SMDs) at post-intervention and short-term follow-up assessments. Our search yielded 23 eligible studies, including 5,298 participants. We found a small to medium favorable effect on distress indicators (SMD=-0.45, 95% CI: -0.56 to -0.34) and a small beneficial effect on positive mental health outcomes (SMD=0.31, 95% CI: 0.14-0.47), which both remained significant at follow-up assessment and were robust in sensitivity analyses. However, our analyses pointed to substantial between-study heterogeneity, which was only partially explained by moderators, and the certainty of evidence was very low across all outcomes. These results provide evidence for the effectiveness of PM+ and SbS in reducing distress indicators and promoting positive mental health in populations exposed to adversities, but a larger high-quality evidence base is needed, as well as research on participant-level moderators of the effects of these interventions, their suitability for stepped-care programs, and their cost-effectiveness.

The mental health impact of the COVID-19 pandemic on older adults: a systematic review and meta-analysis.

BACKGROUND: Early in the COVID-19 pandemic, many experts pointed to potential adverse mental health effects for older adults. By contrast, many studies in young to middle-aged adults found older age to be associated with reduced mental burden. However, a systematic review on older adults is missing. OBJECTIVES: To comprehensively assess the pandemic's mental health impact on older adults. DATA SOURCES: We searched nine databases from December 2019 to April 2022. STUDY SELECTION: We included longitudinal and repeated cross-sectional studies assessing pre- and/or peri-pandemic mental distress and/or positive mental health indicators (e.g. wellbeing) on at least two occasions. DATA SYNTHESIS: We identified 108 studies comprising 102,136 participants (≥60 years). After removal of outliers, there was a small increase in mental distress from pre-to-peri-pandemic assessments, standardised mean difference (SMD) = 0.10, 95% confidence interval (CI) [0.01, 0.18]. Furthermore, a small peri-pandemic decrease in anxiety symptoms was observed, whereas other symptoms remained unchanged. For positive mental health indicators, wellbeing and quality of life showed an initial decrease, whereas overall positive mental health increased during the pandemic, SMD = 0.08, 95% CI [0.01, 0.15]. Being female was related to larger peri-pandemic increases in mental distress. CONCLUSIONS: Based on many studies, this review demonstrated small decreases in mental health during early stages of the pandemic in older adults, with evidence for later recovery. These findings are similar to those for younger adults and correct earlier claims that older adults are at particular risk for negative mental health consequences. The results ask for further research into resilience and adaptation processes in older adults.

Differential associations of leisure music engagement with resilience: A network analysis

Background/Objective: Several factors associated with resilience as the maintenance of mental health despite stress exposure can be strengthened through participation in leisure time activities. Since many people listen to or make music in their leisure time, the aim of the present study was to provide insights into the architecture of how resilience relates to passive and active music engagement. Method: 511 participants regularly listening to and/or making music completed an online survey on resilient outcomes (i.e., mental health and stressor recovery ability), different resilience factors (e.g., optimism, social support), quantitative music engagement (i.e., time spent with music listening/making) and qualitative music engagement (i.e., use of music listening/making for mood regulation). Results: Bivariate correlations showed that subjects spending more time with music making reported better stressor recovery ability and less mental health problems, while partial correlational network analysis revealed no unique associations for quantitative music engagement. Regarding qualitative music engagement, people using music-based mood regulation reported lower mental health, mindfulness, and optimism, but also higher social support. A more heterogeneous pattern emerged for single music-based mood regulation strategies. Conclusions: Our findings highlight the importance of the individual (mal-)adaptive use of music, painting a more nuanced picture of music engagement and resilience. (AU)

To sleep or not to sleep, that is the question: A systematic review and meta-analysis on the effect of post-trauma sleep on intrusive memories of analog trauma.

Distressing intrusive memories of a traumatic event are one of the hallmark symptoms of posttraumatic stress disorder. Thus, it is crucial to identify early interventions that prevent the occurrence of intrusive memories. Both, sleep and sleep deprivation have been discussed as such interventions, yet previous studies yielded contradicting effects. Our systematic review aims at evaluating existing evidence by means of traditional and individual participant data (IPD) meta-analyses to overcome power issues of sleep research. Until May 16th, 2022, six databases were searched for experimental analog studies examining the effect of post-trauma sleep versus wakefulness on intrusive memories. Nine studies were included in our traditional meta-analysis (8 in the IPD meta-analysis). Our analysis provided evidence for a small effect favoring sleep over wakefulness, log-ROM = 0.25, p < .001, suggesting that sleep is associated with a lower number of intrusions but unrelated to the occurrence of any versus no intrusions. We found no evidence for an effect of sleep on intrusion distress. Heterogeneity was low and certainty of evidence for our primary analysis was moderate. Our findings suggest that post-trauma sleep has the potential to be protective by reducing intrusion frequency. More research is needed to determine the impact following real-world trauma and the potential clinical significance.

The Perceived Stress Scale 2&2: a two-factorial German short version of the Perceived Stress Scale.

Background: Stress is among the leading causes for diseases. The assessment of subjectively perceived stress is essential for resilience research. While the Perceived Stress Scale (PSS) is a widely used questionnaire, a German short version of the scale is not yet available. In the current study, we developed such a short version using a machine learning approach for item reduction to facilitate the simultaneous optimization of multiple psychometric criteria. Method: We recruited 1,437 participants from an online panel, who completed the German long version of the PSS along with measures of mental health and resilience. An ant-colony-optimization algorithm was used to select items, taking reliability, and construct validity into account. Findings on validity were visualized by psychological network models. Results: We replicated a bifactor structure for the long version of the PSS and derived a two-factor German short version of the PSS with four items, the PSS-2&2. Its factors helplessness and self-efficacy showed differential associations with mental health indicators and resilience-related factors, with helplessness being mainly linked to mental distress. Conclusion: The valid and economic short version of the PSS lends itself to be used in future resilience research. Our findings highlight the importance of the two-factor structure of the PSS short versions and challenge the validity of commonly used one-factor models. In cases where the general stress factor is of interest, researchers should use the longer versions of the PSS that allow for the interpretation of total scores, while the PSS-2&2 allows of an economic assessment of the PSS factors helplessness and self-efficacy.

The oscillatory fingerprints of self-prioritization: Novel markers in spectral EEG for self-relevant processing.

Self-prioritization is a very influential modulator of human information processing. Still, little is known about the time-frequency dynamics of the self-prioritization network. In this EEG study, we used the familiarity-confound free matching task to investigate the spectral dynamics of self-prioritization and their underlying cognitive functions in a drift-diffusion model. Participants (N = 40) repeatedly associated arbitrary geometric shapes with either "the self" or "a stranger." Behavioral results demonstrated prominent self-prioritization effects (SPEs) in reaction time and accuracy. Remarkably, EEG cluster analysis also revealed two significant SPEs, one in delta/theta power (2-7 Hz) and one in beta power (19-29 Hz). Drift-diffusion modeling indicated that beta activity was associated with evidence accumulation, whereas delta/theta activity was associated with response selection. The decreased beta suppression of the SPE might indicate more efficient sensorimotor processing of self-associated stimulus-response features, whereas the increased delta/theta SPE might refer to the facilitated retrieval of self-relevant features across a widely distributed associative self-network. These novel oscillatory biomarkers of self-prioritization indicate their function as an associative glue for the self-concept.

[Multiple, eruptive epithelioid hemangiomas of the scalp]. / Multiple, eruptive epitheloide Hämangiome der Kopfhaut.

Epithelioid hemangioma is a benign vascular neoplasm with a characteristic histological and immunohistochemical pattern, characterized by a lymphocytic inflammatory infiltrate with admixed eosinophils and FOS­B expression. The correct diagnosis is of particular relevance, since malignant vascular tumors with differentiated epithelioid cells can also be considered in the differential diagnosis. We present a patient with multiple epithelioid hemangiomas of the scalp accompanied by severe pain and itching. The long history of multiple therapeutic attempts illustrates the limited success of currently available treatment options.

The Functional Self.

Current research describes a particular component of the self-concept that influences a wide variety of cognitive processes while it depicts a rather basic component of the self-concept. However, this minimal self seems to be anything but simple; in fact, it seems to be highly functional. Based on previous findings on newly formed self-associations, we put the postulated functionality of this minimal self to another test by retesting its protection mechanisms against negative content. In a pilot experiment, we did not find an overall reduction of negative self-assignments against neutral self-assignments. However, the results indicated an initial difference (as hypothesized) between negative and neutral self-assignments, which decreases over the course of the experiment. We put this interactive effect of valence and block to test in our main experiment, which replicated the data pattern of the pilot experiment. In sum, the results indicate a mandatory integration of stimuli into the self-concept and also a reduction of the integration due to negative valence, thereby supporting a robust protection mechanism.

Transdiagnostic psychosocial interventions to promote mental health in forcibly displaced persons: a systematic review and meta-analysis.

Background: People forced to leave their homes, such as refugees and internally displaced persons, are exposed to various stressors during their forced displacement, putting them at risk for mental disorders.Objective: To summarize evidence on the efficacy of psychosocial interventions aiming to promote mental health and/or to prevent mental symptoms by fostering transdiagnostic skills in forcibly displaced persons of all ages.Method: Four databases and reference lists were searched for randomized controlled trials on interventions in this population on 11 March 2022. Thirty-six studies were eligible, 32 studies (comprising 5299 participants) were included in random-effects multilevel meta-analyses examining the effects of interventions on mental symptoms and positive mental health (e.g. wellbeing) as well as moderators to account for heterogeneity. OSF Preregistration-ID: 10.17605/OSF.IO/XPMU3Results: Our search resulted in 32 eligible studies, with 10 reporting on children/adolescents and 27 on adult populations. There was no evidence for favourable intervention effects in children/adolescents, with 44.4% of the effect sizes pointing to potentially negative effects yet remaining non-significant. For adult populations, our meta-analyses showed a close-to-significant favourable effect for mental symptoms, M(SMD) = 0.33, 95% CI [-0.03, 0.69], which was significant when analyses were limited to high-quality studies and larger for clinical compared to non-clinical populations. No effects emerged for positive mental health. Heterogeneity was considerable and could not be explained by various moderators (e.g. type of control, duration, setting, theoretical basis). Certainty of evidence was very low across all outcomes limiting the generalizability of our findings.Conclusion: The present review provides at most weak evidence for an effect favouring transdiagnostic psychosocial interventions over control conditions for adult populations but not for children and adolescents. Future research should combine the imperative of humanitarian aid in face of major crises with studying the diverse needs of forcibly displaced persons to improve and tailor future interventions.

This review is the first to examine the efficacy of transdiagnostic interventions for mental health promotion and prevention of mental disorders in forcibly displaced persons of all ages.Overall, we found no favourable effect of transdiagnostic interventions in both children/adolescents and adults. Excluding studies at high risk of bias, there was weak evidence for a small favourable effect in adults, but not in children and adolescents. Thus, so far, there is weak evidence for transdiagnostic interventions in forcibly displaced persons.Research efforts need to match care needs: While most people live and need care in low-income countries, the majority of research has been conducted in high-income countries.

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 .

Differential associations of leisure music engagement with resilience: A network analysis.

Background/Objective: Several factors associated with resilience as the maintenance of mental health despite stress exposure can be strengthened through participation in leisure time activities. Since many people listen to or make music in their leisure time, the aim of the present study was to provide insights into the architecture of how resilience relates to passive and active music engagement. Method: 511 participants regularly listening to and/or making music completed an online survey on resilient outcomes (i.e., mental health and stressor recovery ability), different resilience factors (e.g., optimism, social support), quantitative music engagement (i.e., time spent with music listening/making) and qualitative music engagement (i.e., use of music listening/making for mood regulation). Results: Bivariate correlations showed that subjects spending more time with music making reported better stressor recovery ability and less mental health problems, while partial correlational network analysis revealed no unique associations for quantitative music engagement. Regarding qualitative music engagement, people using music-based mood regulation reported lower mental health, mindfulness, and optimism, but also higher social support. A more heterogeneous pattern emerged for single music-based mood regulation strategies. Conclusions: Our findings highlight the importance of the individual (mal-)adaptive use of music, painting a more nuanced picture of music engagement and resilience.

Effects of Upper Body Exercise Training on Aerobic Fitness and Performance in Healthy People: A Systematic Review.

Purpose: This systematic review aimed to evaluate the effects of upper body endurance training (UBET) on oxygen uptake (VO2) in healthy persons and derive evidence-based recommendations to improve upper body fitness and performance. Methods: Databases were systematically searched in accordance with PRISMA guidelines until 1 February 2023. Eligibility criteria included healthy male and female adults and older adults who underwent an UBET intervention. Outcomes of interest included physical fitness (VO2peak and/ or VO2 submax) and transfer effects (i.e., effects from trained (VO2peak ARM) to untrained (VO2peak LEG) musculature). Results: The search identified 8293 records, out of which 27 studies reporting on 29 interventions met our eligibility criteria. The average duration of interventions was 6.8 ± 2.6 weeks with 3.2 ± 0.8 training sessions per week. For 21 of 29 interventions, significant increases in VO2peak ARM were reported following UBET (+16.4% ± 8.3%). Three of the nine studies that analyzed transfer effects of untrained legs after upper body training exhibited significant increases in VO2peak LEG (+9.3% ± 2.6%). Conclusions: This review showed that UBET is a beneficial and useful training modality to increase the oxygen utilization in the upper body. Although UBET is an uncommon form of endurance training in healthy individuals, transfer effects to the untrained muscles can be observed in isolated cases only, rendering transfer effects in UBET inconclusive. Further research should focus on the peripheral changes in muscle morphology of the trained muscles and central changes in cardiovascular function as well as when transfer effects can occur after UBET in healthy people.

Rapid disease progression on immune checkpoint inhibitors in young patients with stage IV melanoma.

Background: Immune checkpoint inhibitors (ICIs) are the standard of care for metastatic cutaneous melanoma (mCM) patients, but their efficacy in young adults aged less than 40 years remains unclear. Materials and methods: We retrospectively analyzed 303 stage IV melanoma patients of different ages treated with nivolumab, pembrolizumab, or ipilimumab plus nivolumab combination therapy. Clinical data and blood values such as LDH, CRP, and absolute immune cell counts were retrieved from the medical records. Pre-treatment serum concentrations of soluble immune checkpoint proteins were measured using ELISA. In addition, information on frequencies of various T cell subsets in the peripheral blood was collected from a previously reported study (ELEKTRA). Patient characteristics and clinical information was correlated with PFS and OS using univariate and multivariate cox regression analysis. Results: Of 303 patients, 33 (11%) were ≤ 40 years old. The older patients had a median age of 64 (95% CI: 61-66). Concerning prognostic parameters, there was no difference between the age groups, e.g., in gender, LDH, or the existence of brain or liver metastases. Patients aged ≤ 40 years [p = 0.014; HR: 1.6 (95% CI: 1.1-2.4)], presence of liver metastases [p = 0.016; HR: 1.4 (95% CI: 1.0-1.9)], line of ICI treatment [p = 0.009; HR: 1.4 (1.0-1.9)], elevated LDH [p = 0.076; HR: 1.3 (95% CI: 0.97-1.8)], and brain metastasis [p = 0.080; HR: 1.3 (95% CI: 0.97-1.7)], were associated with shorter PFS in univariate analysis. Multivariate analysis revealed that the patient's age (≤ 40 years) remains a high-risk factor upon adjusting for all potential confounders [p = 0.067; HR: 1.5 (95% CI: 0.97-2.3)]. Blood parameters revealed that patients ≤ 40 years have relatively higher frequencies of activated CD4 T cells (CD4 + Ki67 + CD4 + ICOS +) in the blood, and significantly lower number of basophils and CD45RA- memory T cells, compared to patients above 40 years (p < 0.05). In addition, patients ≤ 40 years experiencing disease progression within 6 months of ICI treatment had increased concentrations of sPDL1 (p = 0.05) and sTIM3 (p = 0.054) at baseline. Conclusion: Young patients with stage IV melanoma may experience shorter progression-free survival upon ICI treatment compared to patients above 40 years and are characterized by fewer basophils and memory T cells in the blood.