Background: Social support plays an important role for health outcomes. Support for those living with chronic conditions may be particularly important for their health, and even for their survival. The role of support for the survival of cancer patients after receiving an allogeneic hematopoietic cell transplant (alloHCT) is understudied. To better understand the link between survival and support, as well as different sources and functions of support, we conducted two studies in alloHCT patients. First, we examined whether social support is related to survival (Study 1). Second, we examined who provides which support and which specific support-related functions and tasks are fulfilled by lay caregivers and healthcare professionals (Study 2).

Methods: In Study 1, we conducted a retrospective chart review of alloHCT patients (N = 173, 42.8% female, age: M = 49.88) and registered availability of a dedicated lay caregiver and survival. In Study 2, we prospectively followed patients after alloHCT (N = 28, 46.4% female, age: M = 53.97, 46.4% ethnic minority) from the same hospital, partly overlapping from Study 1, who shared their experiences of support from lay caregivers and healthcare providers in semi-structured in-depth interviews 3 to 6 months after their first hospital discharge.

Results: Patients with a dedicated caregiver had a higher probability of surviving to 100 days (86.7%) than patients without a caregiver (69.6%), OR = 2.84, p = 0.042. Study 2 demonstrated the importance of post-transplant support due to patients' emotional needs and complex self-care regimen. The role of lay caregivers extended to many areas of patients' daily lives, including support for attending doctor's appointments, managing medications and financial tasks, physical distancing, and maintaining strict dietary requirements. Healthcare providers mainly fulfilled medical needs and provided informational support, while lay caregivers were the main source of emotional and practical support.

Conclusion: The findings highlight the importance of studying support from lay caregivers as well as healthcare providers, to better understand how they work together to support patients' adherence to recommended self-care and survival.

Retinol binding protein 4 (RBP4) is a member of the lipocalin family and the major transport protein of the hydrophobic molecule retinol, also known as vitamin A, in the circulation. Expression of RBP4 is highest in the liver, where most of the body's vitamin A reserves are stored as retinyl esters. For the mobilization of vitamin A from the liver, retinyl esters are hydrolyzed to retinol, which then binds to RBP4 in the hepatocyte. After associating with transthyretin (TTR), the retinol/RBP4/TTR complex is released into the bloodstream and delivers retinol to tissues via binding to specific membrane receptors. So far, two distinct RBP4 receptors have been identified that mediate the uptake of retinol across the cell membrane and, under specific conditions, bi-directional retinol transport. Although most of RBP4's actions depend on its role in retinoid homeostasis, functions independent of retinol transport have been described. In this review, we summarize and discuss the recent findings on the structure, regulation, and functions of RBP4 and lay out the biological relevance of this lipocalin for human diseases.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a clinically defined, inflammatory central nervous system (CNS) disease of unknown cause, associated with humoral autoimmune findings such as anti-aquaporin 4 (AQP4)-IgG. Recent clinical trials showed a benefit of anti-B cell and anti-complement-antibodies in NMOSD, suggesting relevance of anti-AQP4-IgG in disease pathogenesis.

Objective: AQP4-IgG in NMOSD is clearly defined, yet up to 40% of the patients are negative for AQP4-IgG. This may indicate that AQP4-IgG is not disease-driving in NMOSD or defines a distinct patient endotype.

Methods: We established a biobank of 63 clinically well-characterized NMOSD patients with an extensive annotation of 351 symptoms, patient characteristics, laboratory results and clinical scores. We used phylogenetic clustering, heatmaps, principal component and longitudinal causal interference analyses to test for the relevance of anti-AQP4-IgG.

Results: Anti-AQP4-IgG was undetectable in 29 (46%) of the 63 NMOSD patients. Within anti-AQP4-IgG-positive patients, anti-AQP4-IgG titers did not correlate with clinical disease activity. Comparing anti-AQP4-IgG-positive vs. -negative patients did not delineate any clinically defined subgroup. However, anti-AQP4-IgG positive patients had a significantly (p = 0.022) higher rate of additional autoimmune diagnoses.

Conclusion: Our results challenge the assumption that anti-AQP4-IgG alone plays a disease-driving role in NMOSD. Anti-AQP4-IgG might represent an epiphenomenon associated with NMOSD, may represent one of several immune mechanisms that collectively contribute to the pathogenesis of this disease or indeed, anti-AQP4-IgG might be the relevant factor in only a subgroup of patients.

Background: Measurement of tinnitus-related distress and treatment responsiveness is key in understanding, conceptualizing and addressing this often-disabling symptom. Whilst several self-report measures exist, the heterogeneity of patient populations, available translations, and treatment contexts requires ongoing psychometric replication and validation efforts.

Objective: To investigate the convergent validity and responsiveness of the German versions of the Tinnitus Questionnaire [TQ], Tinnitus Handicap Inventory [THI], and Tinnitus Functional Index [TFI] in a large German-speaking sample of patients with chronic tinnitus who completed a psychologically anchored 7-day Intensive Multimodal Treatment Programme.

Methods: Two-hundred-and-ten patients with chronic tinnitus completed all three questionnaires at baseline and post-treatment. Intraclass correlation coefficients determined the convergent validity of each questionnaire's total and subscale scores. Treatment responsiveness was investigated by [a] comparing treatment-related change in responders vs. non-responders as classified by each questionnaire's minimal clinically important difference-threshold, and [b] comparing agreement between the questionnaires' responder classifications.

Results: The total scores of all three questionnaires showed high agreement before and after therapy (TQ | THI: 0.80 [Pre], 0.83 [Post], TQ | TFI: 0.72 [Pre], 0.78 [Post], THI | TFI: 0.76 [Pre] 0.80 [Post]). All total scores changed significantly with treatment yielding small effect sizes. The TQ and TFI yielded comparable (19.65 and 18.64%) and the THI higher responder rates (38.15%). The TQ | THI and TQ | TFI showed fair, and the THI | TFI moderate agreement of responder classifications. Independent of classification, responders showed significantly higher change rates than non-responders across most scores. Each questionnaire's total change score distinguished between responders and non-responders as classified by the remaining two questionnaires.

Conclusion: The total scores of all three questionnaires show high convergent validity and thus, comparability across clinical and research contexts. By contrast, subscale scores show high inconsistency. Whilst the TFI appears well suited for research purposes, the THI may be better suited to measure psychological aspects of tinnitus-related distress and their changes with accordingly focused treatment approaches.

Background: The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) has been tailored specifically to the demands of patients with persistent depressive disorder (PDD). According to the CBASP model, PDD patients are supposed to live perceptually disconnected from their social environment, which consequently maintains depression. While initially developed as an individual treatment modality, the adaptation for group therapy yields an important interpersonal space. However, little is known about the specific factors that contribute to patients' benefit from the CBASP group modality.

Methods: The analyzed sample comprised N = 87 PDD patients who completed a 12 week multimodal inpatient treatment including 2 weekly CBASP-specific individual and group sessions, respectively, as well as CBASP-unspecific medical contacts, pharmacotherapy and complementary therapies. Group sessions included trainings in situational analysis and interpersonal skills. Interpersonal change over therapy was examined based on the patients' self-perceived interpersonal problems (IIP) and the impact messages as perceived by their individual therapists (IMI). Pre and post-treatment data were compared using within-sample t-tests. Additionally, patients evaluated CBASP group therapy on a feedback form. They were invited to reflect on individual benefits and its helpful and unhelpful aspects. Qualitative content analysis with inductive category development was used to analyze feedback. Inter-rater reliability was computed to confirm categories before summarizing the frequencies of reported factors.

Results: Self-perceived interpersonal distress significantly decreased over therapy. Patients reported reduced interpersonal problems and therapists reported more friendly and dominant impact messages. Interestingly, patients who showed a significant depressive symptom reduction described higher change scores. Regarding qualitative data, patients reported five main benefits from group therapy: Gain in social competence, self-confidence, self-reflection, interpersonal dynamics, and optimism/universality. Patients responding to CBASP identified significantly more factors than non-responders.

Conclusions: Compared to studies with individual CBASP only, the present findings suggest that CBASP group therapy may contribute to the improvement of interpersonal behavior. Group therapy is discussed as a potential boosting effect for individual CBASP. However, as the present data were collected in a multimodal inpatient setting without competitor, randomized controlled trials are warranted that investigate the specific benefits of the group modality or the combined individual and group therapy over individual CBASP only.

The investigation of vascular calcification and its underlying cellular and molecular pathways is of great interest in current research efforts. Therefore, suitable assays are needed to allow examination of the complex calcification process under controlled conditions. The current study describes a new ex vivo model of isolated-perfused rat aortic tissue with subsequent quantification and vessel staining to analyze the calcium content of the aortic wall. A rat aorta was perfused ex vivo with control and calcification media for 14 days, respectively. The calcification medium was luminally perfused and induced a significant increase in calcium deposition within the media of the vessel wall detected alongside the elastic laminae. Perfusion with control medium induced no calcification. In addition, the mRNA expression of the osteogenic marker bone morphogenetic protein 2 (BMP-2) increased in aortic tissue after perfusion, while SM22α as smooth muscle marker decreased. This newly developed ex vivo model of isolated-perfused rat aorta is suitable for vascular calcification studies testing inducers and inhibitors of vessel calcification and studying signaling pathways within calcification progression.

Background: Internal carotid artery occlusion (ICAO) is an important risk factor for stroke. Cerebral hemodynamics in patients with ICAO depends on the individual capacity to activate sufficient collateral pathways. Therefore, the assessment of intracranial collaterals is essential for the acute and long-term management of these patients and accurate estimation of further stroke risk.

Methods: Acute stroke patients with unilateral ICAO were prospectively enrolled. We assessed the following collaterals by transcranial color-coded sonography (TCCS): the anterior and posterior communicating artery (ACoA, PCoA), the ophthalmic artery (OA), and leptomeningeal collaterals of the posterior cerebral artery (LMC). We subdivided the flow pattern of the Doppler spectrum in the middle cerebral artery (MCA) into 3 categories: (1) good, (2) moderate, and (3) bad according to the hemodynamic effects on the ipsilateral MCA flow. Finally, we compared the individual TCCS results with the stroke pattern detected on CT or MRI scan.

Results: One hundred thirteen patients (age 66 +/- 12 years; female 24) were included. The collateral status was good, moderate, and bad in 59 (52%), 37 (33%), and 17 (15%) patients, respectively. The ACoA collateral was most frequently activated (81%), followed by the OA (63%), the PCoA (53%), and the LMC (22%). The quality of the collateral status was determined by the type (p = 0.0003) but not by the number (p = 0.19) of activated collateral pathways. Good collateral function was highly associated with primary collaterals (ACoA > PCoA). Best parameter for a good collateral status was an antegrade flow in the OA, indicating a high blood supply via the communicating arteries.

Conclusions: TCCS allows the assessment of intracranial collaterals and their hemodynamic capacity. Prevalence of collateral sufficiency in ICAO seems to be higher than previously reported. ACoA cross flow is essential for the optimal hemodynamic compensation of ICAO. Antegrade OA flow indicates good collateral status.

Background/Aims: Trajectory of heart rate variability (HRV) represents a noninvasive real-time measure of autonomous nervous system (ANS) and carries the capability of providing new insights into the hemodynamic compensation reserve during hemodialysis (HD). However, studies on HRV reproducibility during HD are scarce and did not refer to different reading periods. In this observational study, we aimed to establish the best suited and most reliable and reproducible HRV index in routine HD treatments including different reading rates. Methods: HRV was characterized by standardized mathematical variation expressions of R/R' intervals: SD of all R/R' intervals (ms), square root of the root mean square of the sum of all differences between adjacent R/R' intervals (ms), percentage of consecutive R/R' intervals that differ by >50 ms (%), low-frequency spectral analysis HRV (LF, expressing sympathetic activity), and high-frequency HRV (HF, expressing parasympathetic activity). To compare robustness of these HRV indices during HD procedures, we compared HRV indices means between different HD sessions and controlled for association with clinical parameters. Results: In 72 HD treatments of 34 patients, we detected the highest reproducibility (89%) of HRV measures when analyzing the low-frequency to high-frequency (LF/HF) ratio in long-term (3 h) readings. Long-term LF/HF was able to discriminate -between patients with and without heart failure NYHA classes >= 3 (p = 0.009) and type 2 diabetes (p = 0.023). We were unable to study relationships between ANS and intradialytic complications because they did not appear in our cohort. Short-term readings of HRV indices did not show any significance of pattern change during HD. Conclusion: In summary, our data provide evidence for high robustness of long-term LF/HF in analyzing HRV in HD patients using future automated monitoring systems. For short-term analysis, mathematical real-time analysis must evolve.

Background: Long-endurance exercises like ultramarathons are known to elicit various metabolic and physiological changes in the human body. However, little is known about very long-duration exercise at low intensities regarding healthy human subjects.

Aim: The purpose of this study was to evaluate changes in body composition and metabolism in long-endurance but low-intensity events.

Methods: Twenty-five male and 18 female healthy recreational athletes (age 34.6 ± 8.8 years; BMI: 22.4 ± 2.0 kg/m2) of the "100 km Mammutmarsch" were recruited for participation during the events in 2014-2016. Other than classical ultramarathons, the "Mammutmarsch" is a hiking event, in which participants were required to walk but not run or jog. It was expected to complete the 100-km distance within 24 h, resulting in a calculated mean speed of 4.17 km/h, which fits to the mean speed observed (4.12 ± 0.76 km/h). As not all participants reached the finish line, comparison of finishers (FIN, n = 11) and non-finishers (NON, n = 21) allowed differential assessment of performance. Body composition measured through bioelectrical impedance analysis (BIA) was determined pre- and post-event, and serum samples were taken pre-event, at 30, 70, and 100 km to determine NT-pro-BNP, troponin T, C-reactive protein (CRP), cortisol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, total cholesterol, total creatine kinase (CK), CK-MB, aminotransferase (AST), ALT, and sodium levels. Nineteen participants wore actimeter armbands (SenseWear®) to gain information about body activity and exercise intensity [metabolic equivalent of task (MET)]. Sixteen participants wore mobile heart rate monitors to assess mean heart rate during the race. Serum parameter alterations over the course of the race were analyzed with mixed-effects ANOVA and additional t-tests. All serum parameters were analyzed for correlation concerning different MET levels, speed, age, BMI, baseline NT-pro-BNP, mean heart rate during the race, and sex with linear regression analysis.

Results: We found significant elevations for muscle and cardiac stress markers (CRP, CK, CK-MB, AST, ALT, cortisol, and NT-pro-BNP) as well as decreasing markers of lipid metabolism (cholesterol, triglycerides, LDL). Although the intensity level demanded from our participants was low compared with other studies on (ultra-) marathons, the alteration of tested parameters was similar to those of high-intensity exercise, e.g., NT-pro-BNP showed a fourfold increase (p < 0.01) and LDL decreased by 20% (p = 0.05). Besides the duration of exercise, age, BMI, training status, and sex are relevant parameters that influence the elevation of stress factors. Notably, our data indicate that NT-pro-BNP might be a marker for cardiovascular fitness also in healthy adults.

Conclusion: This low-intensity long-endurance walk evoked a strong systemic reaction and large cell stress and shifted to a favorable lipid profile, comparable to higher intensity events. Despite increasing cardiac stress parameters, there were no indications of cardiac cell damage. Remarkably, the duration seems to have a greater influence on stress markers and metabolism than intensity.

Background: The benefits of faith-based coping or using religious and spiritual beliefs as a stabilizing force for interpreting stressful or distressing events are largely unexplored among the exodus of Arabic-speaking refugee populations from Muslim-majority countries, particularly those resettled in Europe. The present study aimed to explore the manifestation of faith-based coping strategies among Arabic-speaking refugee adults seeking mental healthcare services in Berlin, Germany and explore how favorable faith-based coping strategies can be optimized from a mental health service-delivery and broader integration perspective.

Methods: A total of 17 qualitative interviews were conducted with Arabic-speaking refugee adults (six females, 11 males) seeking mental health services at the Charite Universitaetsmedizin in Berlin. Research questions aimed to solicit comprehensive perspectives from refugee adults on their mental health, with an emphasis on faith-based coping, and how this facilitated or impeded their integration into German society. Interview transcripts were translated to English from Arabic and analyzed using MAXQDA (2018) to highlight thematic patterns using a grounded theory approach.

Results: Findings were structured into four themes, including: (I) faith-based coping methods during flight, (II) changes in faith practices upon arrival, (III) faith-based coping methods to address distress during integration, and (IV) advice for German mental healthcare providers. Participants who demonstrated a stronger commitment to faith were more likely to utilize faith-based coping strategies when seeking mental health services and facing the challenges of displacement and integration. Examples of faith-based coping included prayer, supplication, reciting scripture, and seeking help from a local religious leader.

Conclusion: The findings suggest how faith and faith practices play a significant role in the mental health and integration of refugee populations in Germany and provide insight on how mental healthcare can be delivered in a culturally-sensitive manner, providing alternatives to the social, cultural, and linguistic barriers posed by the German health system. These findings are particularly relevant for mental health professionals, non-governmental organizations, and humanitarian aid agencies providing mental healthcare to Arabic-speaking populations recently resettled in Western contexts.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by a late clinical onset of psychiatric, cognitive, and motor symptoms. Transcriptional dysregulation is an early and central disease mechanism which is accompanied by epigenetic alterations in HD. Previous studies demonstrated that targeting transcriptional changes by inhibition of histone deacetylases (HDACs), especially the class I HDACs, provides therapeutic effects. Yet, their exact mechanisms of action and the features of HD pathology, on which these inhibitors act remain to be elucidated. Here, using transcriptional profiling, we found that selective inhibition of HDAC1 and HDAC3 by RGFP109 alleviated transcriptional dysregulation of a number of genes, including the transcription factor genes Neurod2 and Nr4a2, and gene sets and programs, especially those that are associated to insulin-like growth factor pathway, in the striatum of R6/1 mice. RGFP109 treatment led to a modest improvement of the motor skill learning and coordination deficit on the RotaRod test, while it did not alter the locomotor and anxiety-like phenotypes in R6/1 animals. We also found, by volumetric MRI, a widespread brain atrophy in the R6/1 mice at the symptomatic disease stage, on which RGFP109 showed no significant effects. Collectively, our combined work suggests that specific HDAC1 and HDAC3 inhibition may offer benefits for alleviating the motor phenotypic deficits and transcriptional dysregulation in HD.

Objectives: Prediction of aortic hemodynamics after aortic valve replacement (AVR) could help optimize treatment planning and improve outcomes. This study aims to demonstrate an approach to predict postoperative maximum velocity, maximum pressure gradient, secondary flow degree (SFD), and normalized flow displacement (NFD) in patients receiving biological AVR.

Methods: Virtual AVR was performed for 10 patients, who received actual AVR with a biological prosthesis. The virtual AVRs used only preoperative anatomical and 4D flow MRI data. Subsequently, computational fluid dynamics (CFD) simulations were performed and the abovementioned hemodynamic parameters compared between postoperative 4D flow MRI data and CFD results.

Results: For maximum velocities and pressure gradients, postoperative 4D flow MRI data and CFD results were strongly correlated (R 2 = 0.75 and R-2 = 0.81) with low root mean square error (0.21 m/s and 3.8 mmHg). SFD and NFD were moderately and weakly correlated at R 2 = 0.44 and R 2 = 0.20, respectively. Flow visualization through streamlines indicates good qualitative agreement between 4D flow MRI data and CFD results in most cases.

Conclusion: The approach presented here seems suitable to estimate postoperative maximum velocity and pressure gradient in patients receiving biological AVR, using only preoperative MRI data. The workflow can be performed in a reasonable time frame and offers a method to estimate postoperative valve prosthesis performance and to identify patients at risk of patient-prosthesis mismatch preoperatively. Novel parameters, such as SFD and NFD, appear to be more sensitive, and estimation seems harder. Further workflow optimization and validation of results seems warranted.

Background: Stress is a major risk factor for the impairment of psychological well-being. The present study aimed to evaluate the empirical evidence of the Transactional Stress Model proposed by Lazarus and Folkman in patients with psychosomatic health conditions.

Methods: A structural equation model was applied in two separate subsamples of inpatients from the Department of Psychosomatic Medicine (total n = 2,216) for consecutive model building (sample 1, n = 1,129) and confirmatory analyses (sample 2, n = 1,087) using self-reported health status information about perceived stress, personal resources, coping mechanisms, stress response, and psychological well-being.

Results: The initial model was created to reflect the theoretical assumptions by Lazarus and Folkman about their transactional stress concept. This model was modified until a sufficient model fit was reached (sample 1: CFI = 0.904, TLI = 0.898, RMSEA = 0.072 [0.071-0.074], SRMR = 0.061). The modified model was confirmed in a second sample (sample 2: CFI = 0.932, TLI = 0.928, RMSEA = 0.066 [0.065-0.068], SRMR = 0.052). Perceived external stressors and personal resources explained 91% of the variance of the stress response, which was closely related to symptoms of depression (63% variance explained). The attenuating effect of resources on stress response was higher (standardized beta = -0.73, p < 0.001) than the impact of perceived stressors on stress response (standardized beta = 0.34, p < 0.001).

Conclusion: The empirical data largely confirmed the theoretical assumption of the Transactional Stress Model, which was first presented by Lazarus and Folkman, in patients with a wide range of psychosomatic conditions. However, data analyses were solely based on self-reported health status. Thus, proposed inner psychological mechanisms such as the appraisal process could not be included in this empirical validation. The operationalization and understanding of coping processes should be further improved.

Platelets are critically involved in murine patent ductus arteriosus (PDA) closure. To date, the clinical significance of these findings in human preterm infants with PDA is still controversial. We discuss the available study data on the role of platelets for PDA closure in preterm infants: Several mostly retrospective studies have yielded conflicting results on whether thrombocytopenia contributes to failed spontaneous ductal closure. The same applies to investigations on the role of thrombocytopenia as a risk factor for unsuccessful ductus arteriosus closure by pharmacological treatment with cyclooxygenase inhibitors. Nonetheless, recent meta-analyses have concluded that thrombocytopenia constitutes an independent risk factor for both failed spontaneous and pharmacological PDA closure in preterm infants. However, the available investigations differ in regard to patient characteristics, diagnostic strategies, and treatment protocols. Several studies suggest that impaired platelet function rather than platelet number is critically involved in failure of ductus arteriosus closure in the preterm infant. A recent randomized-controlled trial on platelet transfusions in preterm infants with PDA failed to show any benefit for liberal vs. restrictive transfusion thresholds on PDA closure rates. Importantly, liberal transfusions were associated with an increased rate of intraventricular hemorrhage, and thus should be avoided. In conclusion, the available evidence suggests that thrombocytopenia and platelet dysfunction contribute to failure of spontaneous and pharmacological PDA closure in preterm infants. However, these platelet effects on PDA seem to be of only moderate clinical significance. Furthermore, platelet transfusions in thrombocytopenic preterm infants in order to facilitate PDA closure appear to cause more harm than good.

In the Western society, non-alcoholic fatty liver disease (NAFLD), characterized by the excessive accumulation of fat in the liver, represents the most common cause of chronic liver disease. If left untreated, approximately 15%-20% of patients with NAFLD will progress to non-alcoholic steatohepatitis (NASH), in which lobular inflammation, hepatocyte ballooning and fibrogenesis further contribute to a distorted liver architecture and function. NASH initiation has significant effects on liver-related mortality, as even the presence of early stage fibrosis increases the chances of adverse patient outcome. Therefore, adequate diagnostic tools for NASH are needed, to ensure that relevant therapeutic actions can be taken as soon as necessary. To date, the diagnostic gold standard remains the invasive liver biopsy, which is associated with several drawbacks such as high financial costs, procedural risks, and inter/intra-observer variability in histology analysis. As liver inflammation is a major hallmark of disease progression, inflammation-related circulating markers may represent an interesting source of non-invasive biomarkers for NAFLD/NASH. Examples for such markers include cytokines, chemokines or shed receptors from immune cells, circulating exosomes related to inflammation, and changing proportions of peripheral blood mononuclear cell (PBMC) subtypes. This review aims at documenting and critically discussing the utility of such novel inflammatory markers for NAFLD/NASH-diagnosis, patient stratification and risk prediction.

Background and Aims: Fluid-attenuated inversion recovery (FLAIR) hyperintense vessels (FHVs) on MRI are a radiological marker of vessel occlusion and indirect sign of collateral circulation. However, the clinical relevance is uncertain. We explored whether the extent of FHVs is associated with outcome and how FHVs modify treatment effect of thrombolysis in a subgroup of patients with confirmed unilateral vessel occlusion from the randomized controlled WAKE-UP trial.

Methods: One hundred sixty-five patients were analyzed. Two blinded raters independently assessed the presence and extent of FHVs (defined as the number of slices with visible FHV multiplied by FLAIR slice thickness). Patients were then separated into two groups to distinguish between few and extensive FHVs (dichotomization at the median <30 or ≥30).

Results: Here, 85% of all patients (n = 140) and 95% of middle cerebral artery (MCA) occlusion patients (n = 127) showed FHVs at baseline. Between MCA occlusion patients with few and extensive FHVs, no differences were identified in relative lesion growth (p = 0.971) and short-term [follow-up National Institutes of Health Stroke Scale (NIHSS) score; p = 0.342] or long-term functional recovery [modified Rankin Scale (mRS) p = 0.607]. In linear regression analysis, baseline extent of FHV (defined as a continuous variable) was highly associated with volume of hypoperfused tissue (β = 2.161; 95% CI 0.96-3.36; p = 0.001). In multivariable regression analysis adjusted for treatment group, stroke severity, lesion volume, occlusion site, and recanalization, FHV did not modify functional recovery. However, in patients with few FHVs, the odds for good functional outcome (mRS) were increased in recombinant tissue plasminogen activator (rtPA) patients compared to those who received placebo [odds ratio (OR) = 5.3; 95% CI 1.2-24.0], whereas no apparent benefit was observed in patients with extensive FHVs (OR = 1.1; 95% CI 0.3-3.8), p-value for interaction was 0.11.

Conclusion: While the extent of FHVs on baseline did not alter the evolution of stroke in terms of lesion progression or functional recovery, it may modify treatment effect and should therefore be considered relevant additional information in those patients who are eligible for intravenous thrombolysis.

Clinical Trial Registration: Main trial (WAKE-UP): ClinicalTrials.gov, NCT01525290; and EudraCT, 2011-005906-32. Registered February 2, 2012.

Student sex work is a current phenomenon all over the world, increasingly reported by the media in recent years. However, student sex work remains under-researched in Germany and is lacking direct first-hand reports from the people involved. Further, sex work remains stigmatized, and therefore, students practicing it could be at risk of social isolation and emotional or physical danger. Therefore, this study examines students working in the sex industry focusing on their personal experiences and attitudes toward them. An online questionnaire was completed by 4386 students from Berlin universities. Students who identified themselves as sex workers (n = 227) were questioned with respect to their motivations to enter the sex industry, characteristics of their job, feelings after the intercourse, and perceived risks. Student non-sex workers (n = 2998) were questioned regarding knowledge of and attitudes toward student sex workers. Most student sex workers reported that they entered the sex industry due to financial reasons (35.7%). The majority reported offering services involving direct sexual intercourse. Disclosing their job to friends, family, or others was associated with less problems with social isolation and in romantic relationships. With a total of 22.9%, student non-sex workers reported never having heard about students working in the sex industry. The most frequent emotions mentioned by them with regard to student sex workers were compassion and dismay (48.9%). There was no difference in happiness between student sex workers and non-sex working students. Through this research, it becomes evident that there are similarities between the student's motivations to enter the sex industry, their feelings, and the problems they have to face. Moreover, prejudices still prevail about the life of student sex workers. Increasing understanding of student sex work might help those sex workers to live a less stigmatized life and thereby to make use of support from others. The universities as institutions could form the basis for this, e.g., by openly supporting student sex workers. This could help to encourage the rights of student sex workers and to gain perspective with respect to the sex industry.

Idiopathic pulmonary fibrosis (IPF) is a progressively and ultimately fatal lung disease. Previously it has been shown that intratracheal administration of alveolar epithelial type II cells (AE2C) in the animal model of bleomycin-induced pulmonary fibrosis is able to reverse fibrosis and restore surfactant protein levels. However, to date, it has not been evaluated whether these changes involve any improvement in alveolar dynamics. Consequently, the aim of the present work was to study lung physiology after AE2C transplantation at different time points during the development of injury and fibrosis. Lung fibrosis was induced by intratracheal instillation of bleomycin (4U/kg) in rat lungs. The animals were transplanted with AE2C (2.5 x 10(6) cells/animal) 3 or 7 days after bleomycin instillation. Assessments were done at day 7 and 14 after the induction of fibrosis to plot time dependent changes in lung physiology and mechanics. To assess the pressures and rates at which closed alveoli reopens invasive pulmonary tests using a small-animal mechanical ventilator (Flexivent (R), Scireq, Canada) including de-recruitability tests and forced oscillation technique as well as quasi-static pressure volume loops were performed. Afterwards lungs were fixed by vascular perfusion and subjected to design-based stereological evaluation at light and electron microscopy level. AE2C delivered during the lung injury phase (3 days) of the disease are only able to slightly recover the volume of AE2C and volume fraction of LB in AE2C. However, it did not show either positive effects regarding ventilated alveolar surface nor any increase of lung compliance. On the other hand, when AE2C are delivered at the beginning of the fibrotic phase (7 days after bleomycin instillation), an increased ventilated alveolar surface to control levels and reduced septal wall thickness can be observed. Moreover, transplanted animals showed better lung performance, with increased inspiratory capacity and compliance. In addition, a detailed analysis of surfactant active forms [mainly tubular myelin, lamellar body (LB)-like structures and multilamellar vesicles (MLV)], showed an effective recovery during the pro-fibrotic phase due to the healthy AE2C transplantation. In conclusion, AE2C transplantation during fibrogenic phases of the disease improves lung performance, structure and surfactant ultrastructure in bleomycin-induced lung fibrosis.

A misdirected or imbalanced local immune composition is often one of the reasons for unsuccessful regeneration resulting in scarring or fibrosis. Successful healing requires a balanced initiation and a timely down-regulation of the inflammation for the re-establishment of a biologically and mechanically homeostasis. While biomaterial-based approaches to control local immune responses are emerging as potential new treatment options, the extent to which biophysical material properties themselves play a role in modulating a local immune niche response has so far been considered only occasionally. The communication loop between extracellular matrix, non-hematopoietic cells, and immune cells seems to be specifically sensitive to mechanical cues and appears to play a role in the initiation and promotion of a local inflammatory setting. In this review, we focus on the crosstalk between ECM and its mechanical triggers and how they impact immune cells and non-hematopoietic cells and their crosstalk during tissue regeneration. We realized that especially mechanosensitive receptors such as TRPV4 and PIEZO1 and the mechanosensitive transcription factor YAP/TAZ are essential to regeneration in various organ settings. This indicates novel opportunities for therapeutic approaches to improve tissue regeneration, based on the immune-mechanical principles found in bone but also lung, heart, and skin.

C-reactive protein (CRP) is the best-known acute phase protein. In humans, almost every type of inflammation is accompanied by an increase of CRP concentration. Until recently, the only known physiological function of CRP was the marking of cells to initiate their phagocytosis. This triggers the classical complement pathway up to C4, which helps to eliminate pathogens and dead cells. However, vital cells with reduced energy supply are also marked, which is useful in the case of a classical external wound because an important substrate for pathogens is disposed of, but is counterproductive at internal wounds (e.g., heart attack or stroke). This mechanism negatively affects clinical outcomes since it is established that CRP levels correlate with the prognosis of these indications. Here, we summarize what we can learn from a clinical study in which CRP was adsorbed from the bloodstream by CRP-apheresis. Recently, it was shown that CRP can have a direct effect on blood pressure in rabbits. This is interesting in regard to patients with high inflammation, as they often become tachycardic and need catecholamines. These two physiological effects of CRP apparently also occur in COVID-19. Parts of the lung become ischemic due to intra-alveolar edema and hemorrhage and in parallel CRP increases dramatically, hence it is assumed that CRP is also involved in this ischemic condition. It is meanwhile considered that most of the damage in COVID-19 is caused by the immune system. The high amounts of CRP could have an additional influence on blood pressure in severe COVID-19.