Search

Die IGES Institut GmbH führte im Auftrag des Sächsischen Staatsministeriums für Soziales und Gesellschaftlichen Zusammenhalt im Zeitraum vom April 2022 bis März 2023 eine Evaluation zur Entbürokratisierung in der Pflege und zur Digitalisierung in den sächsischen Pflegeeinrichtungen durch. Ziel dieser Evaluation war es zu ermitteln, wie sich der aktuelle Stand der Digitalisierung und Dokumentationsentlastung in sächsischen Pflegeeinrichtungen darstellt. Redaktionsschluss: 21.04.2023

BACKGROUND Cell-sized structures such as electrospun mats have been shown to tailor cell growth in a variety of ways and thus have great potential in the development of regenerative implants. Due to their thinness of several hundreds of micrometers, these mats mostly act as coatings on larger matrices, but the use of cytotoxic solvents complicates the translational process. A relatively new technique, melt electrowriting (MEW), offers similar properties but relinquishes cytotoxic solvents. Instead, thermoplastics such as polycaprolactone (PCL) are melted and processed under high voltage to form fibers with a precise fiber diameter that can be deposited in highly ordered meshes using a three-axis system. Outcome of the MEW processes are fiber architectures with defined fiber diameter, fiber spacing and tailored porosity within the cellular dimensions. This contrasts with previous electrospun mats, which mostly exhibit chaotic fiber architectures. RESEARCH QUESTIONS Due to the novelty of MEW, all studies so far used highly customized laboratory printers to produce MEW membranes, complicating translation to the clinic. Therefore, one of the first commercial MEW printer had to be established and the printing characteristics needed to be found to maintain homogeneous fiber diameters throughout the printing process and to investigate the compatibility with other printing techniques. Large tympanic membrane defects, such as those caused by chronic otitis media and other conditions, are currently closed with autologous materials in an elaborate procedure that may result in side effects such as hearing loss. Customized MEW meshes could improve this situation if they demonstrate similar mechanical and vibrational properties as the TM or the respective autologous materials. To this end, the variety of different design parameters such as fiber diameter, fiber spacing, layer-to-layer orientation, and number of layers should be investigated. Ideally, the collagen fiber structure

Das Mammakarzinom ist eine der am häufigsten diagnostizierten Krebserkrankungen bei Frauen in Deutschland. Dank neuer Diagnostikverfahren, wie z.B. Mammographie-Screenings, ist die frühzeitige Erkennung von Mammakarzinomen mit einer Reduktion der Mortalität verbunden. Dennoch ist die Inzidenz von Knochenmetastasen bei Mammakarzinom-Patientinnen mit ca. 73 % im Vergleich zu anderen Krebsarten auffällig hoch. Diese können zu skelettbezogenen Komplikationen führen, wie z.B. Rückenmarkskompressionen und pathologischen Knochenbrüchen. Dadurch wird die Lebensqualität der Patientinnen stark eingeschränkt. Es besteht daher ein großes klinisches Interesse, die Pathogenese von Knochenmetastasen bei Mammakarzinomen besser zu verstehen. Somit können neue Strategien für die Prädiktion und die gezielte Therapie von Knochenmetastasen bei Mammakarzinom-Patientinnen entwickelt werden. Frühere Studien haben gezeigt, dass die Zellmorphologie als Resultat der biochemischen und biophysischen Merkmale von Tumorzellen Informationen über das Metastasierungspotential von Mammakarzinomzellen liefern könnte. Der Fokus dieser Arbeit liegt daher auf dem Zusammenhang zwischen Morphologie und Osteotropismus von Mammakarzinom-Zelllinien, um einen ersten deskriptiven Ansatz zu geben. Dabei wurden verschiedene in vitro-Eigenschaften von einem Zelllinien-Modell aus unterschiedlichen osteotropen Mammakarzinomzellen näher beleuchtet und miteinander verglichen. Dieses in vitro-Modell umfasst die hoch osteotropen Zelllinien, MDA-MB-231MET (MET) und MDA MB 231BONE (BONE) sowie die parentale Zelllinie, MDA-MB-231. Die morphologische Untersuchung ergab 7 unterschiedliche Morphotypen, welche in allen untersuchten Zelllinien in einem stabilen Verhältnis vorlagen. Die Verteilung der Morphotypen war für die jeweilige Zelllinie spezifisch. Bei hoher Konfluenz zeigten MDA-MB-231 und MET ein Wachstum in Einzelzellschicht, während BONE-Zellen dazu tendierten, in vertikaler Ausrichtung zu wachsen. Die eng geknüpften, Mamma carcinoma is one of the most frequently diagnosed cancers in women in Germany. Due to new diagnostic procedures, such as mammography screening, the early detection of mamma carcinoma is associated with a reduction in mortality. Nevertheless, the incidence of bone metastases in mamma carcinoma patients is strikingly high compared to other cancer types, at around 73%. These can lead to major skeletal complications such as spinal cord compression and pathological bone fractures. Thus, the patients' quality of life is severely impacted. Therefore it is of great clinical interest to better understand the pathogenesis of bone metastasis in mamma carcinoma. This will lead to the development of new strategies for the prediction and targeted treatment of bone metastases in mamma carcinoma patients. Previous studies have shown that cell morphology as a result of the biochemical and biophysical properties of tumor cells could provide information about the metastatic potential of mamma carcinoma cells. Therefore, this work focuses on the relationship between morphology and osteotropism of mamma carcinoma cell lines to provide a first descriptive approach. Various in vitro properties of a cell line model comprising different osteotropic mamma carcinoma cell lines were examined and compared with each other. This in vitro model consists of the highly osteotropic cell lines, MDA MB 231MET (MET) and MDA MB 231BONE (BONE), as well as the parental cell line, MDA MB 231. The morphological examination revealed 7 different morphotypes, which were present in a stable ratio in all examined cell lines. The distribution of morphotypes was unique for each cell line. At high confluence, MDA-MB-231 and MET showed growth in a single cell layer, whereas BONE cells tended to grow in a vertical orientation. At low cell density, the tight junctions in MET and BONE were more pronounced than in MDA MB 231. As soon as the cell density further increased, these junctions disappeared in the highly o

Identifying factors that influence age-related cognitive decline is crucial, given its severe personal and societal impacts. However, studying aging in human or animal models is challenging due to the significant variability in aging processes among individuals. Additionally, longitudinal and cross-sectional studies often produce differing results. In this context, home-cage-based behavioral analysis over lifespans has emerged as a significant method in recent years. This study aimed to explore how prior experience affects cognitive performance in mice of various age groups (4, 12, and 22 months) using a home-cage-based touchscreen test battery. In this automated system, group-housed, ID-chipped mice primarily obtain their food during task performance throughout the day, motivated by their own initiative, without being subjected to food deprivation. Spatial working memory and attention were evaluated using the trial unique non-matching to location (TUNL) and the five-choice serial reaction time task (5-CSRTT), respectively. The same set of mice learned both of these demanding tasks. While signs of cognitive decline were already apparent in middle-aged mice, older mice exhibited poorer performance in both tasks. Mice at both 12 and 22 months displayed an increase in perseverance and a decrease in the percentage of correct responses in the TUNL test compared to the 4-month-old mice. Furthermore, during the 5-CSRTT, they exhibited higher rates of omissions and premature responses compared to their younger counterparts. Additionally, the correct response rate in 22-month-old mice was lower than that of the 4-month-old ones. However, mice that had undergone cognitive training at 4 months maintained high-performance levels when re-tested at 12 months, showing an increase in correct responses during TUNL testing compared to their untrained controls. In the 5-CSRTT, previously trained mice demonstrated higher correct response rates, fewer omissions, and reduced premature re, Peer Reviewed

There is a lack of systematic research exploring cross-species variation in liver lobular geometry and zonation patterns of critical drug-metabolizing enzymes, a knowledge gap essential for translational studies. This study investigated the critical interplay between lobular geometry and key cytochrome P450 (CYP) zonation in four species: mouse, rat, pig, and human. We developed an automated pipeline based on whole slide images (WSI) of hematoxylin-eosin-stained liver sections and immunohistochemistry. This pipeline allows accurate quantification of both lobular geometry and zonation patterns of essential CYP proteins. Our analysis of CYP zonal expression shows that all CYP enzymes (besides CYP2D6 with panlobular expression) were observed in the pericentral region in all species, but with distinct differences. Comparison of normalized gradient intensity shows a high similarity between mice and humans, followed by rats. Specifically, CYP1A2 was expressed throughout the pericentral region in mice and humans, whereas it was restricted to a narrow pericentral rim in rats and showed a panlobular pattern in pigs. Similarly, CYP3A4 is present in the pericentral region, but its extent varies considerably in rats and appears panlobular in pigs. CYP2D6 zonal expression consistently shows a panlobular pattern in all species, although the intensity varies. CYP2E1 zonal expression covered the entire pericentral region with extension into the midzone in all four species, suggesting its potential for further cross-species analysis. Analysis of lobular geometry revealed an increase in lobular size with increasing species size, whereas lobular compactness was similar. Based on our results, zonated CYP expression in mice is most similar to humans. Therefore, mice appear to be the most appropriate species for drug metabolism studies unless larger species are required for other purposes, e.g., surgical reasons. CYP selection should be based on species, with CYP2E1 and CYP2D6 being the, Peer Reviewed

Background: The alcohol-attributable burden of disease is high among socially disadvantaged individuals. Interventional efforts intending to have a public health impact should also address the reduction of social inequalities due to alcohol. Objective: The aim was to test the moderating role of educational background on the efficacy of a computer-based brief intervention addressing the full spectrum of alcohol use. Methods: We recruited 1646 adults from the general population aged 18 to 64 years (920 women, 55.9%; mean age 31 years; 574 with less than 12 years of school education, 34.9%) who reported alcohol use in the past year. The participants were randomly assigned a brief alcohol intervention or to assessment only (participation rate, 66.9%, 1646/2463 eligible persons). Recruitment took place in a municipal registry office in one German city. All participants filled out a self-administered, tablet-based survey during the recruitment process and were assessed 3, 6, and 12 months later by study assistants via computer-assisted telephone interviews. The intervention consisted of 3 computer-generated and individualized feedback letters that were sent via mail at baseline, month 3, and month 6. The intervention was based on the transtheoretical model of behavior change and expert system software that generated the feedback letters automatically according to previously defined decision rules. The outcome was self-reported change in number of alcoholic drinks per week over 12 months. The moderator was school education according to highest general educational degree (less than 12 years of education vs 12 years or more). Covariates were sex, age, employment, smoking, and alcohol-related risk level. Results: Latent growth modeling revealed that the intervention effect after 12 months was moderated by educational background (incidence rate ratio 1.38, 95% CI 1.08-1.76). Individuals with less than 12 years of school education increased their weekly alcohol use to a lesser

Background: Atherosclerosis is considered a chronic inflammation of arterial vessels with the involvement of several immune cells causing severe cardiovascular diseases. Lipoprotein apheresis (LA) improves cardiovascular conditions of patients with severely disturbed lipid metabolism. In this context, little is known about the impact of LA on various immune cell populations, especially over time. Methods: Immune cells of 18 LA-naïve patients starting weekly LA treatment were analyzed before and after four apheresis cycles over the course of 24 weeks by flow cytometry. Results and Conclusions: An acute lowering effect of LA on T cell and natural killer (NK) cell subpopulations expressing CD69 was observed. The nonclassical and intermediate monocyte subsets as well as HLA-DR+ 6-sulfo LacNAc+ monocytes were significantly reduced during the apheresis procedure. We conclude that LA has the capacity to alter various immune cell subsets. However, LA has mainly short-term effects than long-term consequences on proportions of immune cells.

Introduction: Isolated redo‐mitral valve replacement (iMVR) is underreported and often mixed up with endocarditis in the present literature. The present study compares first with redo iMVR in noninfective mitral disease. Patients and Methods: A total of 3821 mitral valve procedures were analyzed. The study was restricted to isolated and noninfective mitral valve replacements done by sternotomy. Finally, 402 patients are included, consisting of 102 redo‐ and 300 first surgeries. The mean patient's age was 65.9 ± 10.4 years; the mean EuroSCORE II was 3.0 ± 2.2%. Median follow‐up was 221 days, ranging up to 9.9 years with a total of 367 patient‐years. Results: Redo's had higher EuroSCORE II (5.1 ± 2.9% vs. 2.3 ± 1.4%; p < .01), more atrial fibrillation (31.1% vs. 46.1%; p = .01), chronic obstructive pulmonary disease (7.3% vs. 17.6%; p = .05), coronary artery disease (7.3% vs. 17.6%; p = .03) and more frequently reduced ejection fraction < 30% (3.0% vs. 11.8%; p = .02). Main outcomes showed comparable 30‐days mortality (first: 4.1%, redo: 6.9%; p = .813). Postoperative morbidity of the redo's was associated with increased postoperative bleeding (p < .01) resulting in increased transfusions of packed red blood cells and fresh frozen plasma (each p < .01), more re‐explorations (p < .01) and longer primary intensive care unit stay (p < .01). Postoperative occurrence of stroke, respiratory or renal failure, and myocardial infarction as well as hospital stay differed not significantly. Estimated 5‐years survival was 65.5 ± 12.3% for all patients with no significant differences between the groups. Multivariate logistic regression respiratory failure as relevant for hospital (odds ratio [OR]: 12.3 [1.1–158]; p = .029) and stroke (OR: 4.8 [1.1–12.3]; p = .021) as relevant for long‐term mortality. Conclusion: iMVR for noninfective reasons is infrequent and rare. Compared to primary surgery, redo's suffer mainly from bleeding‐associated morbidity. This does not translate into pr

Objective. This study aimed to determine the predictors of olfactory improvement after endoscopic sinus surgery among patients with chronic rhinosinusitis with nasal polyps. Method. This prospective cohort study included patients admitted to a university hospital between 2006 and 2012. Assessment using odour identification testing, a sinonasal symptom questionnaire, the Rhinosinusitis Disability Index and mucus biomarker levels was performed at various time points. Correlation of variables with identification score differences at six postoperative time points and at baseline was performed, followed by multiple linear regression to determine significant predictors at each of the six post-operative time points. Results. Baseline absence of acute sinusitis, elevated serpin F2 and anterior rhinorrhoea predict early olfactory improvement, whereas baseline allergic rhinitis predicts late olfactory improvement. Baseline odour identification score was the strongest predictor across all time points. Conclusion. Patients with chronic rhinosinusitis and nasal polyps with worse disease or baseline olfactory function may benefit more from endoscopic sinus surgery in terms of olfactory improvement.

In T cells, processes such as migration and immunological synapse formation are accompanied by the dynamic reorganization of the actin cytoskeleton, which has been suggested to be mediated by regulators of RhoGTPases and by F-actin bundlers. SWAP-70 controls F-actin dynamics in various immune cells, but its role in T cell development and function has remained incompletely understood. CD4+ regulatory T (Treg) cells expressing the transcription factor Foxp3 employ diverse mechanisms to suppress innate and adaptive immunity, which is critical for maintaining immune homeostasis and self-tolerance. Here, we propose Swap-70 as a novel member of the Foxp3-dependent canonical Treg cell signature. We show that Swap-70-/- mice have increased numbers of Foxp3+ Treg cells with an effector/memory-like phenotype that exhibit impaired suppressor function in vitro, but maintain overall immune homeostasis in vivo. Upon formation of an immunological synapse with antigen presenting cells in vitro, cytosolic SWAP-70 protein is selectively recruited to the interface in Treg cells. In this context, Swap-70-/- Treg cells fail to downregulate CD80/CD86 on osteoclast precursor cells by trans-endocytosis and to efficiently suppress osteoclastogenesis and osteoclast function. These data provide first evidence for a crucial role of SWAP-70 in Treg cell biology and further highlight the important non-immune function of Foxp3+ Treg cells in bone homeostasis mediated through direct SWAP-70-dependent mechanisms.

Treatment of infective endocarditis can often prove challenging due to its wide range of anatomical presentations. When complicated by an aortic root abscess, patients may require extensive root surgery, which on its own leads to a worse outcome. We present our experience with a surgical technique for reinforcing the aortic annulus with a ring from a Dacron aortic prosthesis placed in the left ventricular outflow tract to avoid the need for root replacement procedures or patch closures of the defect. The technique described in this paper provides a viable alternative to the standard techniques used for the treatment of annular abscesses in aortic valve endocarditis. Due to the relative simplicity and ease of use, this approach may present a means of reducing operation time and possibly postoperative complications of this severe condition.

In der Schriftenreihe werden die Ergebnisse einer einjährigen Ammoniak-Messkampagne im sächsischen Luftgütemessnetz in unterschiedlicher zeitlicher und räumlicher Auflösung dargestellt. An der untersuchten Verkehrsstation konnte ein großer Teil des gemessenen Ammoniaks mit der Hintergrundkonzentration und/oder dem Transport von außerhalb der Stadt in Verbindung gebracht werden. Ein direkter Einfluss von lokalen Verkehrsemissionen auf die Ammoniak-Konzentrationen am Standort Borna konnte nicht nachgewiesen werden. Messungen mit einer derartigen zeitlichen Auflösung von 1 Stunde existieren in Deutschland nur wenige. Die Veröffentlichung richtet sich an die Fachöffentlichkeit. Redaktionsschluss: 28.02.2024

Essential tremor (ET) is the most common movement disorder worldwide and is characterized by an isolated tremor of the upper limb that worsens over the course of time. Evidence has accumulated to support the theory that the cerebellum is primary involved in the development of ET disease, although the contribution of cerebellar pathology to ET’s aetiology remains poorly understood. Beside motor deficits, numerous studies report the presence of cognitive impairment in ET patients. The cerebellum is crucial for motor as well as cognitive functions as it integrates sensorimotor information to create an internal model of movement using prediction errors. In this study, I tested the performance of 34 ET patients and 34 age-matched healthy controls in a visuomotor adaptation (VMA) task whose proper execution critically depends on the cerebellum. Participants performed the VMA while sitting in front of a computer screen. At the beginning of each trial, eight grey circles in one of eight possible positions arrayed around a central cross appeared on the screen. Next, one of the eight circles was marked as a blue target, and participants had to move from the central cross towards the target using a digital pen moved on a digital tablet. The movement on the tablet was represented as a cursor on the screen. Visual feedback from the moving hand was prevented. Over the course of the experiment, a 30° clockwise visuomotor perturbation of the cursor movement on the screen was introduced abruptly. To this end, subjects implicitly modified the reach direction such that they are able to hit the target again. The extent to which a subject adapts to the visuomotor perturbation can be measured by the angular error between a straight line connecting the center cross and the target, and a line connecting the center cross and the position of the cursor at peak velocity. Reaction times and movement times were analyzed to assess motor performance. In accordance with my hypothesis, I found evid

Theoretical background: Considerable progress has been made in illuminating the neural basis of the compulsive use patterns characterizing substance use disorders. It has been suggested to utilize these findings to alleviate the health burden associated with substance use. Objective: We address how neuroimaging research can provide these benefits. Methods: Based on neurobiological models of addiction, we highlight neuroimaging research elucidating neural predictors of relapse and how treatments modify these markers. Results: With the focus on cue reactivity, brain activity related to the motivational salience of drugs and automatized use behaviors can predict relapse. Cue reactivity changes with abstinence, and it remains to be determined whether such changes confer periods of critical relapse susceptibility. Conclusions: Several established and emerging interventions modulate brain activity associated with drug value. However, executive deficits in addiction may compromise interventions targeting control-related prefrontal brain areas. Lastly, it remains more difficult to change the brain responses mediating habitual behaviors., Theoretischer Hintergrund: Es wurden beträchtliche Fortschritte im Verständnis der neuronalen Grundlagen der für Substanzkonsumstörungen charakteristischen kompulsiven Konsummuster erzielt. Diese Erkenntnisse könnten genutzt werden, um die mit dem Substanzkonsum verbundene gesundheitliche Belastung zu mindern. Fragestellung: Wir untersuchen, wie neurobiologische Forschung zu diesem Ziel beitragen kann. Methoden: Basierend auf neurobiologischen Modellen der Sucht beleuchten wir Arbeiten, die neuronale Prädiktoren von Rückfallen identifizieren und zeigen, wie Interventionen diese Marker verändern. Ergebnisse: Es zeigt sich, dass Cue Reactivität im Zusammenhang mit der motivationalen Bedeutung von Drogen und automatisiertem Konsumverhalten Rückfalle vorhersagen kann. Cue Reactivität verändert sich mit Abstinenz, und es bleibt zu klären, ob solche Veränderungen die Rückfallanfälligkeit beeinflussen. Schlussfolgerungen: Mehrere etablierte und neuere Interventionen modulieren Gehirnaktivität, die mit dem Anreizwert von Drogen assoziiert ist. Exekutivdefizite könnten die Wirkung von Interventionen beeinträchtigen, welche die Nutzung kontrollrelevanter präfrontaler Hirnareale erfordern. Schließlich ist es nach wie vor schwieriger Gehirnaktivität zu verändern, die habituelle Verhaltensweisen mediiert.

Objective: Type 1 diabetes is associated with autoantibodies to different organs that include the gut. The objective of the study was to determine the risk of developing gastric parietal cell autoimmunity in relation to other autoimmunity in individuals with a family history of type 1 diabetes. Methods: Autoantibodies to the parietal cell autoantigen, H+/K+ ATPase subunit A (ATP4A) was measured in 2218 first-degree relatives of patients with type 1 diabetes, who were prospectively followed from birth for a median of 14.5 years. All were also tested regularly for the development of islet autoantibodies, transglutaminase autoantibodies, and thyroid peroxidase autoantibodies. Results: The cumulative risk to develop ATP4A autoantibodies was 8.1% (95% CI, 6.6–9.6) by age 20 years with a maximum incidence observed at age 2 years. Risk was increased in females (HR, 1.9; 95% CI, 1.3–2.8; p = 0.0004), relatives with the HLA DR4-DQ8/DR4-DQ8 genotype (HR, 3.4; 95% CI, 1.9–5.9; p < 0.0001) and in participants who also had thyroid peroxidase autoantibodies (HR, 3.7; 95% CI, 2.5– 5.5; p < 0.0001). Risk for at least one of ATP4A-, islet-, transglutaminase-, or thyroid peroxidase-autoantibodies was 24.7% (95% CI, 22.6–26.7) by age 20 years and was 47.3% (95% CI, 41.3–53.3) in relatives who had an HLA DR3/DR4-DQ8, DR4-DQ8/ DR4-DQ8, or DR3/DR3 genotype (p < 0.0001 vs. other genotypes). Conclusions: Relatives of patients with type 1 diabetes who have risk genotypes are at very high risk for the development of autoimmunity against gastric and other organs.

Background Perinatal markers of prenatal development are associated with offspring psychiatric symptoms. However, there is little research investigating the specificity of perinatal markers for the development of specific disorders. This study aimed to explore if perinatal markers are specifically associated with adolescent substance use disorder (SUDs). Methods Adolescent participants from two study centers, one for SUD patients (n = 196) and one for general psychopathology (n = 307), were recruited for participation. Since the SUD participants presented with a number of comorbid disorders, we performed a 1-on-1 matching procedure, based on age, gender, and specific pattern of comorbid disorders. This procedure resulted in n = 51 participants from each group. From all participants and their mothers we recorded perinatal markers (mode of birth, weeks of completed pregnancy, birth weight, Apgar score after 5 min) as well as intelligence quotient (IQ). The SUD sample additionally filled out the Youth Safe Report (YSR) as well as the PQ-16 and the DUDIT. We aimed to distinguish the two groups (SUD sample vs. general psychiatric sample) based on the perinatal variables via a logistic regression analysis. Additionally, linear regressions were performed for the total group and the subgroups to assess the relationship between perinatal variables and IQ, YSR, DUDIT and PQ-16. Results The perinatal variables were not able to predict group membership (X2 [4] = 4.77, p = .312, Cox & Snell R² = 0.053). Odds ratios indicated a small increase in probability to belonging to the general psychiatric sample instead of the SUD sample if birth was completed via C-section. After Bonferroni-correction, the linear regression models showed no relation between perinatal markers and IQ (p = .60, R² = 0.068), YSR (p = .09, R² = 0.121), DUDIT (p = .65, R² = 0.020), and PQ-16 (p = .73, R² =0.021).

Aims: To examine whether personality traits predict the course of addictive behaviours in general and whether predictive associations differ between non-substance related (NR) and substance related (SR) addictive behaviours. Methodology: We recruited 338 individuals (19–27 y, 59 % female) from a random community sample with NR, SR, or no DSM-5 addictive disorder. Predictors were the Big Five personality traits (NEO-FFI) and reward and punishment sensitivity (BIS/BAS questionnaire). Outcomes were the slopes of addictive behaviours (i. e., quantity, frequency, and number of DSM-5 criteria) over three years. Bayesian multiple regressions were used to analyse the probabilities for each hypothesis. Results: The evidence that higher neuroticism, lower conscientiousness, lower agreeableness, higher extraversion, lower openness, higher reward sensitivity, and lower punishment sensitivity predict increased addictive behaviours over time was, overall, moderate to high (69 % to 99 %) and varied by trait and outcome. Predictive associations were mostly higher for NR compared with SR addictive behaviours. Conclusions: Personality traits predict the course of addictive behaviours, but associations were only about half as large as expected. While some personality traits, such as lower conscientiousness, predict increases in both NR and SR addictive behaviours over time, others, such as lower punishment sensitivity, seem to specifically predict increases in NR addictive behaviours., Zielsetzung: Untersuchung der Vorhersage des Verlaufs von abhängigem Verhalten durch Persönlichkeitsmerkmale und Prüfung, ob sich diese prädiktiven Assoziationen zwischen verhaltensbezogenem (VB) und substanzbezogenem (SB) abhängigen Verhalten unterscheiden. Methodik: Wir rekrutierten 338 Personen (19–27 Jahre, 59 % weiblich) aus einer kommunalen Zufallsstichprobe mit einer VB-, einer SB- oder keiner DSM-5-Abhängigkeit. Prädiktoren waren die „Big Five“-Persönlichkeitsmerkmale (NEO-FFI) und die Belohnungs- und Bestrafungssensitivität (BIS/BAS-Fragebogen). Die Outcomes waren der Verlauf des abhängigen Verhaltens (d. h. Menge und Häufigkeit des Konsums und Anzahl der erfüllten DSM-5-Kriterien) über drei Jahre. Zur Analyse der Wahrscheinlichkeiten für jede Hypothese wurden Bayes‘sche multiple Regressionsanalysen verwendet. Ergebnisse: Die Evidenz, dass höherer Neurotizismus, geringere Gewissenhaftigkeit, geringere Verträglichkeit, höhere Extraversion, geringere Offenheit, höhere Belohnungssensitivität und geringere Bestrafungssensitivität eine Zunahme von Merkmalen abhängigen Verhaltens im Laufe der Zeit vorhersagen, war insgesamt moderat bis hoch (69 % bis 99 %) und variierte je nach Persönlichkeitsmerkmal und Outcome. Die prädiktiven Assoziationen waren meist höher für VB im Vergleich zu SB abhängigen Verhalten. Schlussfolgerungen: Persönlichkeitsmerkmale sagen den Verlauf des abhängigen Verhaltens voraus, allerdings waren die Zusammenhänge nur etwa halb so groß wie erwartet. Während einige Persönlichkeitsmerkmale, wie z. B. eine geringere Gewissenhaftigkeit, im Laufe der Zeit eine Zunahme des VB und des SB abhängigen Verhaltens vorhersagen, scheinen andere, wie z. B. eine geringere Sensibilität für Bestrafung, speziell eine Zunahme des VB abhängigen Verhaltens vorherzusagen.

Introduction: Allogeneic hematopoietic cell transplantation (HCT) during chemotherapy-induced aplasia may offer long-term survival in acute myeloid leukemia (AML) with otherwise poor prognosis including ELN adverse risk, relapsed or refractory disease. However, the value of residual morphologic disease prior HCT in this context has not been conclusively settled until yet. Therefore, we aimed to investigate variables predicting outcome in this unique setting of sequential conditioning therapy, with a focus on pretreatment morphologic blast count. In contrast to the most popular FLAMSA-RIC protocol, we used a melphalan-based conditioning regimen during aplasia. Methods: We retrospectively analyzed data from 173 AML patients who underwent a sequential melphalan-based conditioning therapy between 2003 and 2015 at our centre. All patients participated either in the prospective Phase 2 BRIDGE trial (NCT01295307), the Phase 3 AML2003 study (NCT00180102) or were treated according to this protocol and underwent allogeneic HCT after melphalan-based conditioning in treatment-induced aplasia. Results: Median bone marrow blast count prior to conditioning was 10% (range, 0–96%). Four year probabilities of EFS and OS were 34% (95% CI, 28–43%) and 43% (95% CI, 36–52%), respectively. In multivariate analysis, blast count >20% was associated with worse EFS (HR = 1.93; p = 0.009) and OS (HR = 1.80; p = 0.026). This effect was not significant anymore for HCT during 1st line therapy. Conclusion: Allogeneic HCT in aplasia with a melphalan-based conditioning regimen has the potential to cure a subset of adverse risk AML patients, even with persistent morphological disease prior HCT. However, a high pre-transplant blast count still indicates patients with a dismal prognosis, especially in the relapsed patient group, for whom post-transplant strategies should be considered to further optimize post HCT outcome.

Background and Purpose. Tibial head fracture (THF) rehabilitation is still a challenge in clinical practice. Short-term use of continuous passive motion (CPM) postoperatively for THFs can increase knee range of motion (ROM) immediately, and its effect on enhanced rehabilitation also ended when the CPM application was discontinued. The aim of this study was to investigate the effect on the recovery of prolonged use of CPM in the postoperative treatment of THFs. Methods. 60 patients with THFs were randomly and equally divided into the CPM group and non-CPM group. Both groups immediately received CPM and conventional physical therapies during hospitalization. After discharge, the non-CPM group was treated with conventional physical therapy alone, while the CPM group received conventional physical training in combination with CPM treatment. At 6 weeks and 6 months postoperatively, the primary outcome which was knee ROM and the secondary outcome which was knee functionality and quality of life were evaluated. Results. The CPM group had a significantly increased ROM at both follow-up time points. The Knee Society Score, UCLA activity score, and the EuroQoL as well as the pain analysis showed significantly better results of the CPM group than the non-CPM group. Conclusions. The prolonged application of CPM therapy is an effective method to improve the postoperative rehabilitation of THFs.

Background: Renal denervation (RDN) can reduce cardiac sympathetic activity maintained by arterial hypertension (aHT). Its potential antiarrhythmic effect on rhythm outcome in patients with multi-drug resistant aHT undergoing catheter ablation for atrial fibrillation (AF) is unclear. Methods: The RDN+AF study was a prospective, randomized, two-center trial. Patients with paroxysmal or persistent AF and uncontrolled aHT (mean systolic 24-h ambulatory BP > 135 mmHg) despite taking at least three antihypertensive drugs were enrolled. Patients were 1:2 randomized to either RDN+AF ablation or AF-only ablation. Primary endpoint was freedom from any AF episode > 2 min at 12 months assessed by implantable loop recorder (ILR) or 7d-holter electrocardiogram. Secondary endpoints included rhythm outcome at 24 months, blood pressure control, periprocedural complications, and renovascular safety. Results: The study randomized 61 patients (mean age 65 ± 9 years, 53% men). At 12 months, RDN+AF patients tended to have a greater decrease in ambulatory BPs but did not reach statistical significance. No differences in rhythm outcome were observed. Freedom from AF recurrence in the RDN+AF and AF-only group measured 61% versus 53% p = .622 at 12 months and 39% versus 47% p = .927 at 24 months, respectively. Periprocedural complications occurred in 9/61 patients (15%). No patient died. Conclusion: Among patients with multidrug-resistant aHT and paroxysmal or persistent AF, concomitant RDN+AF ablation was not associated with better blood pressure control or rhythm outcome in comparison to AF-only ablation and medical therapy.

HIV und sexuell übertragbare Infektionen sind gut behandelbar, wenn sie früh erkannt werden. Unter den im Flyer angeführten Adressen finden Sie kostenlose und vertrauliche Beratungs- und Testangebote in Sachsen. Redaktionsschluss: 31.03.2024

Background The study aimed to investigate the link between burnout symptoms and prosocial behaviour, as well as the role of acute stress and vagally-mediated heart rate variability (vmHRV) on this association. Methods Seventy men were randomly assigned to either the stress or the control condition of the Trier Social Stress Test for Groups (TSST-G). Prosocial behaviour was assessed via a social decision-making paradigm during the respective TSST-G condition. Results Correlation analyses revealed negative correlations between prosocial behaviour and burnout symptoms. Acute stress was also associated with reduced prosocial behaviour, whereas no interaction effects with burnout symptoms could be revealed. Exploratory analyses showed that vmHRV was negatively correlated with burnout symptoms during the social decision-making paradigm but did not mediate the link between burnout and prosocial behaviour. Conclusion In conclusion, we report first experimental evidence that burnout symptoms are negatively associated with prosocial behaviour. Further studies are needed to explore the causal relations.

1. Bibliometric study in pediatric minimally invasive surgery (MIS) Pediatric MIS is a standard technique worldwide for many pediatric surgical diseases and we aimed to analyze the research activity in this field. Articles on pediatric MIS (1991–2020) were analyzed from the Web of ScienceTM for the total number of publications, citations, journals, and IFs. Of these, the 50 most cited publications were evaluated in detail and classified according to the level of evidence (i.e., study design) and topic (i.e., surgical procedure). In total, 4464 publications and 53,111 citations from 684 journals on pediatric MIS were identified. The 50 most cited papers were published from 32 institutions in the USA/Canada (n = 28), Europe (n = 19), and Asia (n = 3) in 12 journals. Four authors (USA/Europe) contributed to 26% of the 50 most cited papers as first/senior author. Hot topics were laparoscopic pyeloplasty (n = 9), inguinal hernia repair (n = 7), appendectomy, and pyloromyotomy (n = 4 each). The majority of publications were retrospective studies (n = 33) and case reports (n = 6) (IF 5.2 ± 3.2; impact index 16.5 ± 6.4; citations 125 ± 39.4). They were cited as often as articles with high evidence levels (meta-analyses, n = 2; randomized controlled trials, n = 7; prospective studies, n = 2) (IF 12.9 ± 22.5; impact index 14.0 ± 6.5; citations 125 ± 34.7; p > 0.05). 2. Altmetric study in pediatric surgery Altmetric analysis assessing online mentions of publications is a new method to evaluate awareness to research output. We aimed to identify and characterize the top 100 articles with the highest Altmetric Attention Score (AAS) in pediatric surgery. Publications from core pediatric surgical journals (J Pediatr Surg, J Pediatr Surg Case Rep, Eur J Pediatr Surg, European J Pediatr Surg Rep, Pediatr Surg Int, Semin Pediatr Surg) were retrieved from www.altmetric.com in January 2023 and the top 100 publications were identified. Characteristics of each publication were analyzed. P

Objectives: To investigate which spaces stroke patients visit in their free time while undergoing inpatient recovery in rehabilitation centers, what activities they engage in, and what kind of spaces they want. Background: Research studies consistently show that stroke patients are highly inactive during rehabilitation. Much remains unknown about what patients do in their free time and how the built environment might affect their behavior and activities. Methods: Patients’ free-time activities were recorded via patient shadowing (n = 70, 840 hr), and their spatial preferences were collected using a survey (n = 60) in seven rehabilitation centers. Each participant was observed over one typical day (12 consecutive hours). Their activities, durations, and locations were recorded using floor plans and time log sheets. Results: Six main themes emerged from the analysis of shadowing data and patient surveys: (1) spending most free time in their room, (2) corridor as the overlooked activity hub, (3) food and beverage stations as triggers of activity, (4) wanting to socialize, (5) variety of common spaces for different activities is desired, and (6) common room’s atmosphere, comfort, style, and view are important. Even though socializing with other patients was mentioned as a primary reason for visiting common spaces in the survey, patients spent most of their free time alone. Conclusions: Corridor emerged as a space with great potential to motivate and support various activities of patients. Patients’ free-time activities could contribute to their recovery, and the built environment may play a role in facilitating and supporting these activities.

Der Forschungsbericht beinhaltet die Ergebnisse der Studie „Erfahrungsraum praktische Pflegeausbildung“ (ERPP-Studie Sachsen 2023). Es handelt sich dabei um eine Begleitstudie, welche in der ersten Phase des Modellprojektes „Beratungsstelle Pflegeausbildung Sachsen“ vom September 2022 bis August 2023 durchgeführt wurde. Dieses Projekt war an der Technischen Universität Dresden an der Professur Gesundheit und Pflege/Berufliche Didaktik angesiedelt und wurde vom Sächsischen Staatsministerium für Soziales und Gesellschaftlichen Zusammenhalt gefördert. Die Studie beinhaltete eine multiperspektivische Analyse in Bezug auf verschiedene Themenkomplexe der praktischen Pflegeausbildung in Sachsen. Es werden die Hintergründe für Ausbildungsabbrüche im Pflegeberuf 1.), die speziellen Herausforderungen der Praxisanleitung 2.), die Formen und Probleme der Lernortkooperation 3.) sowie die Bedarfe an Unterstützungs- und Beratungsangeboten 4.), in Bezug auf die Akteursgruppen der Auszubildenden, Praxisanleitenden, Pflegelehrenden und Pflegedienstleitenden, untersucht. Das Vorgehen der Forschung ist von einer Methodentriangulation gekennzeichnet, weshalb im Bericht sowohl qualitative und quantitative Forschungsergebnisse präsentiert werden. Der vorliegende Forschungsbericht bietet eine multiperspektivische Darstellung zentraler Herausforderungen und Gestaltungsmöglichkeiten der praktischen Pflegeausbildung in Sachsen. Neben der Präsentation und Diskussion der Ergebnisse werden zudem praxisnahe Empfehlungen formuliert. Der Bericht richtet sich damit gleichermaßen an Pflegedienstleitende, Praxisanleitende, Pflegelehrende und Auszubildende im Pflegeberuf.:GELEITWORT 2 VORWORT 4 1. ZUSAMMENFASSUNG DER STUDIE 10 1.1 Themenkomplex: Ausbildungsabbrüchen begegnen 10 1.2 Themenkomplex: Herausforderungen und Gelingensbedingungen der Praxisanleitung ..12 1.3 Themenkomplex: Lernortkooperationen ausgestalten und Schnittstellenprobleme identifizieren 13 1.4 Themenkomplex: Beratungs- und Unterstüt

Objectives: Quality of life (QOL) is increasingly used as indicator in health research. The aim of this paper was an updated psychometric validation and a new standardization of the German version of the EUROHIS-QOL using a sample of the German general population assessed in 2021. The study focused on socio-economic characteristics and on anxiety and depressiveness as major indicators of mental health. Methods: With 8 items, the EUROHIS-QOL is an economical instrument for self-assessment. Results: Statistical tests revealed good psychometric properties. Gender- and age-group-specific norm values were calculated. The EUROHIS-QOL showed good discriminant validity for anxiety and depression symptoms. Participants without clinically relevant scores for depressiveness and anxiety reported significantly higher QOL. Multiple regression analysis showed that unemployment, younger age, not living with a partner, and an immigrant background were important predictors of lower QOL, whereas higher income, living in one's own home, and a high level of education predicted higher QOL. Conclusion: The EUROHIS-QOL was confirmed as an economical and reliable instrument for assessing QOL in the German general population.

Hintergrund. Deutschland gehörte im Jahr 2019 zu den Ländern mit dem weltweit höchsten Pro-Kopf-Alkoholkonsum, welcher wesentlich zur Krankheitslast beiträgt. Fragestellung. In dieser Modellierungsstudie schätzen wir, wie viele alkoholbedingte inzidente Krankheits- sowie Todesfälle in Deutschland im Jahr 2019 hätten vermieden werden können, wenn die derzeitigen Verbrauchssteuern auf Alkohol um 20%, 50% und 100%erhöht worden wären. Methodik. Ausgangspunkt für die Modellierung sind die spezifischen Verbrauchssteuern auf alkoholische Getränke in Deutschland. Drei Szenarien wurden unter der Annahme, dass die resultierende Steuererhöhung vollständig in den Verkaufspreis übertragen wird, und unter Verwendung von getränkespezifischen Preiselastizitäten modelliert. Mittels des sich daraus ergebenden Rückgangs im jährlichen Pro-Kopf-Konsum und der krankheitsspezifischen Risikofunktionen wurde die vermeidbare alkoholbedingte Inzidenz bzw. Mortalität geschätzt. Berücksichtigt wurden alkoholbedingte Erkrankungen des Herz-Kreislauf- und Verdauungssystems, Alkoholabhängigkeit, Epilepsie, Infektionskrankheiten sowie Verletzungen und Unfälle. Ergebnisse. Insgesamt hätten durch eine Verdoppelung der spezifischen Verbrauchssteuern auf Alkohol im Jahr 2019 bis zu 200.400 alkoholbedingte Erkrankungs- und Verletzungsfälle sowie 2800 Todesfälle vermieden werden können. Dies entspricht knapp 7% der berücksichtigten alkoholbedingten Krankheits- bzw. Todesfälle in Deutschland. Diskussion. Alkoholbedingte Erkrankungen und Verletzungen sind vermeidbar und eine Erhöhung der spezifischen Verbrauchssteuern auf alkoholische Getränke in Deutschland könnte die alkoholbedingte Krankheitslast substanziell reduzieren., Background. In 2019, Germany was among the countries with the highest alcohol per capita consumption in the world, which contributes significantly to the burden of disease. Aim. In this modelling study, we estimate how many alcohol-attributable diseases and deaths in Germany could have been avoided in 2019 if current alcohol excise taxes were increased by 20%, 50%, and 100%. Methods. The starting point for the modelling was the national beverage-specific alcohol taxes. Three scenarios were modelled under the assumption that the resulting tax increase would be fully transferred to the retail prices. Beverage-specific price elasticities were used. Based on the estimated resulting decline in annual per capita consumption and the disease-specific risk functions, we modelled the avoidable incidence and mortality for alcohol-attributable diseases for 2019. Alcohol-attributable diseases of the cardiovascular and digestive systems, alcohol dependence, epilepsy, and infectious diseases as well as injuries and accidentswere considered. Results. Overall, doubling the beveragespecific alcohol taxes could have avoided up to 200,400 alcohol-attributable cases of disease and injury as well as 2800 deaths in Germany in 2019. This corresponds to just under 7% of the modelled new alcohol-attributable cases of disease and death in Germany. Discussion. Alcohol-attributable diseases and injuries are preventable and an increase in the alcohol taxes could substantially reduce the alcohol-attributable burden of disease in Germany.

Mechanical stimulation plays a crucial role in promoting cell differentiation. However, applying physical force directly to cells requires complex equipment and a sterile environment, posing challenges. To overcome this, stimuli-responsive biomaterials or 4D scaffolds can serve as an alternative platform for mechanical stimulation. These scaffolds, fabricated using advanced 3D printing techniques, can apply the necessary force to cells. To optimize their functionality, bioactive molecules or extracellular matrices can be incorporated or decorated on their surfaces. This thesis proposal focuses on developing a versatile material platform that allows customization through systematic composition adjustment and on-demand printing, while also offering surface modification capabilities. The primary objective is to create a novel cell carrier platform using thermo-responsive polymers. By manipulating the additive monomer compositions, we can finely adjust properties such as the transition temperature of the polymers, tailoring them to specific requirements. Furthermore, this platform will enable the fabrication of complex three-dimensional biomaterial structures with controllable porosity, a critical aspect of biomaterial design. Leveraging the capabilities of three-dimensional printing technology, we can program and achieve desired porosity levels in the printed structures, providing enhanced flexibility for biomaterial design. The development of thermo-responsive scaffolds involved three distinct stages aimed at designing an optimized platform that effectively operates within the physiological range while ensuring cell viability. One of the key challenges was to achieve a balance between thermoresponsive behavior and biocompatibility. In the initial stage, we investigated the interplay between a crosslinkable three-armed macromer (trimethylolpropane triacrylate-TMPTA) and various monomers (N-isopropylacrylamide-NiPAAm, methyl methacrylate-MMA, dimethylaminoethyl acrylate

Nicht selten stellt Sie der herausfordernde Pflegealltag wahrscheinlich auch vor Situationen, die Sie körperlich und emotional belasten. Die Fachservicestelle Sachsen, die im Auftrag des Sächsischen Sozialministeriums tätig ist, hilft bei der Orientierung in den Angeboten und unterstützt bei der Suche nach den richtigen Ansprechpartnern vor Ort. Redaktionsschluss: 30.04.2024

Aim: Despite the lack of evidence, current resuscitation guidelines recommend tactile stimulation in apneic infants within the first minutes of life. The aim was to investigate whether timing, duration or intensity of tactile stimulation influences the extent of non-invasive respiratory support in extremely preterm infants during neonatal resuscitation. Methods: In an observational study, we analyzed 47 video recordings and physiological parameters during postnatal transition in preterm infants below 320/7 weeks of gestational age. Infants were divided into three groups according to the intensity of respiratory support. Results: All infants were stimulated at least once during neonatal resuscitation regardless of their respiratory support. Only 51% got stimulated within the first minute. Rubbing the feet was the preferred stimulation method and was followed by rubbing or touching the chest. Almost all very preterm infants were exposed to stimulation and manipulation most of the time within their first 15 min of life. Tactile stimulation lasted significantly longer but stimulation at multiple body areas started later in infants receiving prolonged non-invasive respiratory support. Conclusion: This observational study demonstrated that stimulation of very preterm infants is a commonly used and easy applicable method to stimulate spontaneous breathing during neonatal resuscitation. The concomitant physical stimulation of different body parts and therefore larger surface areas might be beneficial.

Die myotone Dystrophie ist eine autosomal dominant vererbte, multisystemische Erkrankung mit skelettmuskulärem Fokus und wird in zwei Untergruppen eingeteilt, die myotone Dystrophie Typ I (MD1), verursacht durch eine CTG-Trinukleotidexpansion im DMPK-Gen auf Chromosom 19, und die myotone Dystrophie Typ II (MD2), verursacht durch eine Tetranukleotidexpansion im CNBP-Gen auf Chromosom 3. Die Nukleotidexpansionen akkumulieren als mRNA intranukleär und tragen über die Beeinflussung des alternativen Splicings von über 30 Genen zum Erkrankungsmechanismus bei. Daneben akkumulieren die mRNA-Repeats im Zytoplasma und induzieren über die Repeat-assoziierte-non-AUG-Translation (RAN-Translation) die Akkumulation aberranter Proteine. Wenngleich die Patienten der MD2 einen milderen Krankheitsverlauf erleben, zeigen sie ein erhöhtes Auftreten von Autoimmunerkrankungen. In der Pathogenese der Autoimmunerkrankungen spielt die durch Interferon-Typ-I vermittelte Immunreaktion eine wichtige Rolle. In der AG Günther konnte eine erhöhte Expression interferonstimulierter Gene und die erhöhte Expression von Markern des Stresszustandes des endoplasmatischen Retikulums in Fibroblasten von MD2-Patienten nachgewiesen sowie die erhöhte Prävalenz von Autoimmunerkrankungen in MD2 gezeigt werden. Die Auswertung serologischer Parameter im Rahmen dieser Arbeit erlaubte eine klinische Charakterisierung der Patienten und ergab einen positiven Zusammenhang zwischen Höhe der Myoglobin-Konzentration im Serum und Länge der CCTG Repeats. Es wurde die Hypothese aufgestellt, dass die zytoplasmatischen RNA-Repeats über die RAN-Translation und Akkumulation aberranter Proteine zur Induktion von ER-Stress führen, welcher über die gemeinsame Kontaktflächen der Mitochondrien-assoziierten Membranen (MAMs) in die Mitochondrien übertragen wird. Im Rahmen des mitochondrialen Stresszustandes könnte es zu einer Freisetzung mitochondrialer DNA und zur Aktivierung des zytosolischen DNA-Rezeptors cGAS und einer nachfolgend

Pathogenic variants in KCNA2, encoding for the voltage-gated potassium channel Kv1.2, have been identified as the cause for an evolving spectrum of neurological disorders. Affected individuals show early-onset developmental and epileptic encephalopathy, intellectual disability, and movement disorders resulting from cerebellar dysfunction. In addition, individuals with a milder course of epilepsy, complicated hereditary spastic paraplegia, and episodic ataxia have been reported. By analyzing phenotypic, functional, and genetic data from published reports and novel cases, we refine and further delineate phenotypic as well as functional subgroups of KCNA2-associated disorders. Carriers of variants, leading to complex and mixed channel dysfunction that are associated with a gain- and loss-of-potassium conductance, more often show early developmental abnormalities and an earlier onset of epilepsy compared to individuals with variants resulting in loss- or gain-of- function. We describe seven additional individuals harboring three known and the novel KCNA2 variants p.(Pro407Ala) and p.(Tyr417Cys). The location of variants reported here highlights the importance of the proline(405)–valine(406)–proline(407) (PVP) motif in transmembrane domain S6 as a mutational hotspot. A novel case of self-limited infantile seizures suggests a continuous clinical spectrum of KCNA2-related disorders. Our study provides further insights into the clinical spectrum, genotype–phenotype correlation, variability, and predicted functional impact of KCNA2 variants.

Knowledge about cardiac and inflammatory biomarkers in patients with stable coronary artery disease (CAD) is limited. To address this, we analyzed 3072 patients (36% female) with a median follow-up of 10 years in the Leipzig LIFE Heart Study with suspected CAD with coronary angiography. Selected biomarkers included troponin T (hsTNT), N-terminal pro B-type natriuretic peptide (NT-proBNP), copeptin, C-reactive protein (hsCRP), and interleukin-6 (IL-6). Patients were stratified by CAD severity: CAD0 (no sclerosis), CAD1 (non-obstructive, i.e., stenosis < 50%), and CAD2 (one stenosis 50%). Group comparison (GC) included GC1: CAD0 + 1 vs. CAD2; GC2: CAD0 vs. CAD1 + 2. CAD0, CAD1, and CAD2 were apparent in 1271, 631, and 1170 patients, respectively. Adjusted for classical risk factors, hs-cTnT, NT-proBNP, and IL-6 differed significantly in both GC and hsCRP only in GC2. After multivariate analysis, hs-cTnT, NT-proBNP, and IL-6 remained significant in GC1. In GC2, hs-cTnT (p < 0.001) and copeptin (p = 0.014) reached significance. Ten-year survival in groups CAD0, CAD1, and CAD2 was 88.3%, 77.3%, and 72.4%. Incorporation of hs-cTnT, NT-proBNP, copeptin, and IL-6 improved risk prediction (p < 0.001). The studied cardiac and inflammatory biomarkers enable fast and precise non-invasive identification of mortality risk in CAD patients, allowing the tailoring of primary and secondary CAD prevention.

Objective: To evaluate the 5-year real-world benefit–risk profile of fingolimod in patients with relapsing–remitting MS (RRMS) in Germany. Methods: Post-Authorization Non-interventional German sAfety study of GilEnyA (PANGAEA) is a non-interventional realworld study to prospectively assess the effectiveness and safety of fingolimod in routine clinical practice in Germany. The follow-up period comprised 5 years. Patients were included if they had been diagnosed with RRMS and had been prescribed fingolimod as part of clinical routine. There were no exclusion criteria except the contraindications for fingolimod as defined in the European label. The effectiveness and safety analysis set comprised 4032 and 4067 RRMS patients, respectively. Results: At the time of the 5-year follow-up of PANGAEA, 66.57% of patients still continued fingolimod therapy. Annualized relapse rates decreased from baseline 1.5 ± 1.15 to 0.42 ± 0.734 at year 1 and 0.21 ± 0.483 at year 5, and the disability status remained stable, as demonstrated by the Expanded Disability Status Scale mean change from baseline (0.1 ± 2.51), the decrease of the Multiple Sclerosis Severity Score from 5.1 ± 2.59 at baseline to 3.9 ± 2.31 at the 60-months follow-up, and the percentage of patients with ‘no change’ in the Clinical Global Impression scale at the 60-months follow-up (78.11%). Adverse events (AE) occurring in 75.04% of patients were in line with the known safety profile of fingolimod and were mostly non-serious AE (33.62%) and non-serious adverse drug reactions (50.59%; serious AE 4.98%; serious ADR 10.82%). Conclusions: PANGAEA demonstrated the sustained beneficial effectiveness and safety of fingolimod in the long-term realworld treatment of patients with RRMS.

Brain-derived neurotrophic factor (BDNF), an important neural growth factor, has gained growing interest in neuroscience, but many influencing physiological and analytical aspects still remain unclear. In this study we assessed the impact of storage time at room temperature, repeated freeze/thaw cycles, and storage at 80 C up to 6 months on serum and ethylenediaminetetraacetic acid (EDTA)-plasma BDNF. Furthermore, we assessed correlations of serum and plasma BDNF concentrations in two independent sets of samples. Coefficients of variations (CVs) for serum BDNF concentrations were significantly lower than CVs of plasma concentrations (n = 245, p = 0.006). Mean serum and plasma concentrations at all analyzed time points remained within the acceptable change limit of the inter-assay precision as declared by the manufacturer. Serum and plasma BDNF concentrations correlated positively in both sets of samples and at all analyzed time points of the stability assessment (r = 0.455 to rs = 0.596; p < 0.004). In summary, when considering the acceptable change limit, BDNF was stable in serum and in EDTA-plasma up to 6 months. Due to a higher reliability, we suggest favoring serum over EDTA-plasma for future experiments assessing peripheral BDNF concentrations.

Background: Therapeutic and salutogenic effects of psychedelic drugs have been attributed to psychotherapeutic or psychotherapy-like processes that can unfold during the acute psychedelic experience and beyond. Currently, there are no psychometric instruments available to comprehensively assess psychotherapeutic processes (as conceptualized by empirical psychotherapy research) in the context of psychedelic experiences. Aims: We report the initial validation of the General Change Mechanisms Questionnaire (GCMQ), a self-report instrument designed to measure five empirically established general change mechanisms (GCMs) of psychotherapy—(1) resource activation, (2) therapeutic relationship, (3) problem actuation, (4) clarification, and (5) mastery—in the context of psychedelic experiences. Methods: An online survey in a sample of 1153 English-speaking and 714 German-speaking psychedelic users was conducted to evaluate simultaneously developed English- and German-language versions of the GCMQ. Results: The theory-based factor structure was confirmed. The five GCMQ scales showed good internal consistency. Evidence for convergent validity with external measures was obtained. Significant associations with different settings and with therapeutic, hedonic, and escapist use motives confirmed the hypothesized context dependence of GCM-related psychedelic experiences. Indicating potential therapeutic effects, the association between cumulative stressful life events and well-being was significantly moderated by resource activation, clarification, and mastery. Factor mixture modeling revealed five distinct profiles of GCM-related psychedelic experiences. Conclusion: Initial testing indicates that the GCMQ is a valid and reliable instrument that can be used in future clinical and nonclinical psychedelic research. The five identified profiles of GCM-related experiences may be relevant to clinical uses of psychedelics and psychedelic harm reduction., Peer Reviewed

Autism spectrum disorder (ASD) is characterized by impaired social interaction and communication skills, repetitive behaviors, restricted interests, and specific sensory processing. Particularly, adults with high-functioning ASD often remain unrecognized, presumably due to their high compensatory skills, but at the cost of high stress, which is often linked to anxiety and depression. This may further explain the significantly high suicide rates and reduced life expectancy among individuals with ASD. Thus, providing support to high-functioning autistic adults in managing core symptoms, as well as co-occurring anxiety and depression, appears essential. To date, only a limited number of evidence-based psychosocial therapeutic options are available, and very few of them have undergone rigorous evaluation in a clinical context. To obtain a comprehensive understanding, a systematic literature search was conducted according to the PRISMA checklist, and only studies demonstrating robust methodological quality were included and discussed in this review article. Although promising initial key factors and methods have been identified, additional evidence-based studies are imperative to ascertain the optimal treatment and evaluate the long-term outcomes for adults with high-functioning ASD., Peer Reviewed

Serotonin is an essential neuromodulator for mental health and animals’ socio-cognitive abilities. However, we previously found that a constitutive depletion of central serotonin did not impair rat cognitive abilities in stand-alone tests. Here, we investigated how a mild and acute decrease in brain serotonin would affect rats’ cognitive abilities. Using a novel rat model of inducible serotonin depletion via the genetic knockdown of tryptophan hydroxylase 2 (TPH2), we achieved a 20% decrease in serotonin levels in the hypothalamus after three weeks of non-invasive oral doxycycline administration. Decision making, cognitive flexibility, and social recognition memory were tested in low-serotonin (Tph2-kd) and control rats. Our results showed that the Tph2-kd rats were more prone to choose disadvantageously in the long term (poor decision making) in the Rat Gambling Task and that only the low-serotonin poor decision makers were more sensitive to probabilistic discounting and had poorer social recognition memory than other low-serotonin and control individuals. Flexibility was unaffected by the acute brain serotonin reduction. Poor social recognition memory was the most central characteristic of the behavioral network of low-serotonin poor decision makers, suggesting a key role of social recognition in the expression of their profile. The acute decrease in brain serotonin appeared to specifically amplify the cognitive impairments of the subgroup of individuals also identified as poor decision makers in the population. This study highlights the great opportunity the Tph2-kd rat model offers to study inter-individual susceptibilities to develop cognitive impairment following mild variations of brain serotonin in otherwise healthy individuals. These transgenic and differential approaches together could be critical for the identification of translational markers and vulnerabilities in the development of mental disorders., This research was funded by the Deutsche Forschungsgemeinschaft (grant number RI 2474/2-1 to Marion Rivalan and AL 1197/5-1 to Natalia Alenina), by the Deutsche Forschungsgemeinschaft to the Center of Excellence NeuroCure DFGEXC 257, and by the EU H2020 MSCA ITN projects ‘‘Serotonin and Beyond’’ to Natalia Alenina and Michael Bader (grant number N 953327)., Deutsche Forschungsgemeinschaft, Deutsche Forschungsgemeinschaft to the Center of Excellence NeuroCure DFGEXC 257, EU H2020 MSCA ITN projects ‘‘Serotonin and Beyond’’ to Natalia Alenina and Michael Bader, Peer Reviewed

Childhood stroke can lead to lifelong disability. Developing algorithms for timely recognition of clinical and paraclinical signs is crucial to ensure prompt stroke diagnosis and minimize decision-making time. This study aimed to characterize clinical and paraclinical symptoms of childhood and neonatal stroke as relevant diagnostic criteria encountered in clinical practice, in order to develop algorithms for prompt stroke diagnosis. The analysis included data from 402 pediatric case histories from 2010 to 2016 and 108 prospective stroke cases from 2017 to 2020. Stroke cases were predominantly diagnosed in newborns, with 362 (71%, 95% CI 68.99–73.01) cases occurring within the first 28 days of birth, and 148 (29%, 95% CI 26.99–31.01) cases occurring after 28 days. The findings of the study enable the development of algorithms for timely stroke recognition, facilitating the selection of optimal treatment options for newborns and children of various age groups. Logistic regression serves as the basis for deriving these algorithms, aiming to initiate early treatment and reduce lifelong morbidity and mortality in children. The study outcomes include the formulation of algorithms for timely recognition of newborn stroke, with plans to adopt these algorithms and train a fuzzy classifier-based diagnostic model using machine learning techniques for efficient stroke recognition., The research was founded by [17.000418.80.07A] the project “Evaluation of incidence, prevalence, risk factors, research of clinical, neuroimaging, neurophysiological, and neurotrophic remedial aspects of cerebrovascular accidents in children” within the state program “Systemogenesis of risk factors, optimization of the medical assistance service, evaluation sustainable and mathematical modeling of Stroke”., “Evaluation of incidence, prevalence, risk factors, research of clinical, neuroimaging, neurophysiological, and neurotrophic remedial aspects of cerebrovascular accidents in children” within the state program “Systemogenesis of risk factors, optimization of the medical assistance service, evaluation sustainable and mathematical modeling of Stroke”, Peer Reviewed

Introduction: Ayurveda, South Asia’s largest and most relevant system of Traditional Medicine, holds a legal status akin to conventional Western medicine in India and elsewhere. There is an almost complete lack of data on the use of Ayurveda in Germany. The aim of this study was to investigate Ayurveda’s utilization patterns, entry points, and factors influencing its use and the perception of Ayurveda among the German population. Methods: Basis of this manuscript was an online-representative survey which involved 4,065 participants aged 18–75 about the use and acceptance of Traditional, Complementary and Integrative Medicine (TCIM) in Germany. The survey was conducted online using Computer Assisted Web Interview (CAWI) in 2022. The dataset was analyzed descriptively and inferentially. Results: Altogether 9.3% (n = 377) of all survey participants (n = 4,065) had already used Ayurveda somehow, either more often (1.7%) or at least once in a lifetime (7.6%). Responders associated Ayurveda primarily with Indian Medicine (27.7%) and wellness (18%). Commonly used Ayurvedic services included non-medical treatments at wellness resorts/spas (48.3%), in outpatient practices (27.1%), and hotels (23.6%). 30.2% of the participants believe in Ayurveda’s therapeutic potential. 76.7% of Ayurveda users find healthy nutrition important or very important. Nine predictors were found to classify Ayurveda users vs. non-users with spirituality and belief in Ayurveda’s therapeutic efficacy as the most relevant ones. Ayurveda seems to be primarily used by well-educated and female individuals, often from higher-income groups and with a rather modern social milieu-orientation. Conclusion: Study results suggest that about every tenth German citizen has used Ayurveda in the past and about one third believes in its therapeutic potential. Because Ayurvedic therapies are often not evidence-based, there is an urgent need to perform high quality randomized controlled trials to investigate potential e, Peer Reviewed

Rheumatoid arthritis (RA) is a debilitating autoimmune condition characterized by chronic synovitis, joint damage, and inflammation, leading to impaired joint functionality. Existing RA treatments, although effective to some extent, are not without side effects, prompting a search for more potent therapies. Recent research has revealed the critical role of FAS-associated death domain protein (FADD) microvesicular shedding in RA pathogenesis, expanding its scope beyond apoptosis to include inflammatory and immune pathways. This study aimed to investigate the intricate relationship between mi-RNA 128a, autoimmune and inflammatory pathways, and adenosine levels in modulating FADD expression and microvesicular shedding in a Freund’s complete adjuvant (FCA) induced RA rat model and further explore the antirheumatoid potency of trimetazidine (TMZ). The FCA treated model exhibited significantly elevated levels of serum fibrogenic, inflammatory, immunological and rheumatological diagnostic markers, confirming successful RA induction. Our results revealed that the FCA-induced RA model showed a significant reduction in the expression of FADD in paw tissue and increased microvesicular FADD shedding in synovial fluid, which was attributed to the significant increase in the expression of the epigenetic miRNA 128a gene in addition to the downregulation of adenosine levels. These findings were further supported by the significant activation of the TLR4/MYD88 pathway and its downstream inflammatory IkB/NFB markers. Interestingly, TMZ administration significantly improved, with a potency similar to methotrexate (MTX), the deterioration effect of FCA treatment, as evidenced by a significant attenuation of fibrogenic, inflammatory, immunological, and rheumatological markers. Our investigations indicated that TMZ uniquely acted by targeting epigenetic miRNA128a expression and elevating adenosine levels in paw tissue, leading to increased expression of FADD of paw tissue and mitigated F, Peer Reviewed

The article processing charge was funded by the Open Access Publication Fund of Humboldt-Universität zu Berlin., Background: In light of the aging population, increasingly suffering from the metabolic syndrome (MS), strategies need to be developed to address global public health challenges known to be associated with MS such as arthritis. As physical activity (PA) may play a crucial role in tackling those challenges, this study aimed to determine the association between the number of MS risk factors, PA and arthritis in people ≥ 50 years old. Methods: Data from the Survey of Health, Ageing, and Retirement in Europe (SHARE) were used to estimate the prevalence of arthritis and MS risk factors in the European population ≥ 50 years and to evaluate the associations between MS risk factors, PA and arthritis. Binary logistic regression was performed to calculate the odds ratio of different factors. Results: 73,125 participants were included in the analysis. 55.75% of patients stated at least one of the three MS risk factors. The prevalence of rheumatoid arthritis (RA) and osteoarthritis (OA)/other rheumatism among ≥ 50 years population was 10.19% and 19.32% respectively. Females showed a higher prevalence of arthritis than males. Prevalence did not differ between groups with different levels of PA. Arthritis prevalence was positively correlated with the number of MS risk factors (P < 0.01) but not with PA (P > 0.05). Conclusion: Middle-aged and older Europeans with multiple comorbidities suffered from RA, OA or other rheumatism more frequently than participants with fewer comorbidities, while the level of physical activity was not associated with the number of metabolic risk factors in patients with RA and OA/other rheumatism., Peer Reviewed

Background: The high prevalence of injuries in female athletes necessitates a course of action that not only enhances research in this field but also incorporates improved prevention programs and regular health monitoring of highly stressed structures such as tendons and muscles. Since myometry is already used by coaches and physiotherapists, it is important to investigate whether tissue stiffness varies in different types of sports, and whether such measures are affected by an acute training session. Methods: Myometric measurements of the Achilles tendon (AT) and soleus muscle (SM) were performed in the longitudinal plane and relaxed tendon position. In total, 38 healthy professional female athletes were examined, applying a quasi-experimental study design, with subgroup analysis performed for different sports. To investigate the stiffness of the AT and SM, 24 female handball and volleyball athletes performed a standardized maximal incremental performance test on a treadmill. In this subgroup, myometric measurements were taken before and after the exercise test. Results: The measurements showed no significant difference between the mean pre- (AT: 661.46 N/m; SM 441.48 N/m) and post-exercise stiffness (AT: 644.71 N/m; SM: 439.07 N/m). Subgroup analysis for different types of sports showed significantly lower AT and SM stiffness in swimming athletes compared to handball (p = 0.002), volleyball (p = 0.000) and hammer throw athletes (p = 0.008). Conclusions: Myometry can be performed on the same day as an acute training session in healthy female professional volleyball and handball athletes. Female swimmers have significantly lower AT and SM stiffness compared to female handball, volleyball and hammer throw athletes. These results show that the stiffness differences in the AT and SM can be assessed by myometry., This research received no external funding., Peer Reviewed

There is an association between sleep quality and glioma-specific outcomes, including survival. The critical role of sleep in survival among subjects with glioma may be due to sleep-induced activation of brain drainage (BD), that is dramatically suppressed in subjects with glioma. Emerging evidence demonstrates that photobiomodulation (PBM) is an effective technology for both the stimulation of BD and as an add-on therapy for glioma. Emerging evidence suggests that PBM during sleep stimulates BD more strongly than when awake. In this study on male Wistar rats, we clearly demonstrate that the PBM course during sleep vs. when awake more effectively suppresses glioma growth and increases survival compared with the control. The study of the mechanisms of this phenomenon revealed stronger effects of the PBM course in sleeping vs. awake rats on the stimulation of BD and an immune response against glioma, including an increase in the number of CD8+ in glioma cells, activation of apoptosis, and blockage of the proliferation of glioma cells. Our new technology for sleep-phototherapy opens a new strategy to improve the quality of medical care for patients with brain cancer, using promising smart-sleep and non-invasive approaches of glioma treatment., Russian Science Foundation, Peer Reviewed

Objective The goal of this research was to demonstrate the efficacy of telemedicine via design, implementation and evaluation of a web-based remote patient monitoring system (WB-RPMS) across the tertiary/university teaching hospitals in a developing country Nigeria, as a tool to continue to expand access to an affordable and resilient tertiary healthcare system through the challenging times of the COVID-19 pandemic or any future disruptions. Methods This research employed an agile and human-centred design thinking philosophy, which saw the researchers iteratively collaborate with clinicians across the system development value chain. It also employed qualitative and quantitative research methods for new system evaluations. After the system's development, a 20-patient sample was randomly selected from members of the National Youth Service Corp to evaluate the WB-RPMS Patient Portal for usability and user experience through a survey based on the system usability scale. Again, the COREQ standards for reporting research result were adopted for this study. Results The evaluation of the WB-RPMS Patient Portal by a select patient sample showed that 95.0% of the respondents believed that they would like to use the system frequently. It was also discovered that 90.0% of all respondents also indicated that they found the Patient Portal to be simple; 85.0% of the respondents believed and indicated that the WB-RPMS Patient Portal was easy to use. Conclusions The result of the usability evaluation of the developed WB-RPMS Patient Portal showed that it was well received by the select patient sample and by the clinicians who participated in the development process. In fact, the performance of the system shows that it has the potential to remotely support and sustain improved access to affordable healthcare for outpatients in developing countries even during times of uncertainties and disruptions as recently occasioned by COVID-19 pandemic., Peer Reviewed

Introduction The emergence of new SARS-CoV-2 variants, capable of escaping the humoral immunity acquired by the available vaccines, together with waning immunity and vaccine hesitancy, challenges the efficacy of the vaccination strategy in fighting COVID-19. Improved therapeutic strategies are urgently needed to better intervene particularly in severe cases of the disease. They should aim at controlling the hyperinflammatory state generated on infection, reducing lung tissue pathology and inhibiting viral replication. Previous research has pointed to a possible role for the chaperone HSP90 in SARS-CoV-2 replication and COVID-19 pathogenesis. Pharmacological intervention through HSP90 inhibitors was shown to be beneficial in the treatment of inflammatory diseases, infections and reducing replication of diverse viruses. Methods In this study, we investigated the effects of the potent HSP90 inhibitor Ganetespib (STA-9090) in vitro on alveolar epithelial cells and alveolar macrophages to characterise its effects on cell activation and viral replication. Additionally, the Syrian hamster animal model was used to evaluate its efficacy in controlling systemic inflammation and viral burden after infection. Results In vitro, STA-9090 reduced viral replication on alveolar epithelial cells in a dose-dependent manner and lowered significantly the expression of proinflammatory genes, in both alveolar epithelial cells and alveolar macrophages. In vivo, although no reduction in viral load was observed, administration of STA-9090 led to an overall improvement of the clinical condition of infected animals, with reduced oedema formation and lung tissue pathology. Conclusion Altogether, we show that HSP90 inhibition could serve as a potential treatment option for moderate and severe cases of COVID-19., http://dx.doi.org/10.13039/501100002347Bundesministerium für Bildung und Forschung, http://dx.doi.org/10.13039/501100013865Stiftung Charité, http://dx.doi.org/10.13039/501100006188Einstein Stiftung Berlin, http://dx.doi.org/10.13039/501100001659Deutsche Forschungsgemeinschaft, http://dx.doi.org/10.13039/501100001656Helmholtz-Gemeinschaft, Peer Reviewed

Objective: Providing country-level estimates for prevalence rates of Generalized Anxiety Disorder (GAD), COVID-19 exposure and food insecurity (FI) and assessing the role of persistent threats to survival—exemplified by exposure to COVID-19 and FI—for the mental health crisis in Africa. Methods: Original phone-based survey data from Mozambique, Sierra Leone, Tanzania and Uganda (12 consecutive cross-sections in 2021; n = 23,943) were analyzed to estimate prevalence rates of GAD. Logistic regression models and mediation analysis using structural equation models identify risk and protective factors. Results: The overall prevalence of GAD in 2021 was 23.3%; 40.2% in Mozambique, 17.0% in Sierra Leone, 18.0% in Tanzania, and 19.1% in Uganda. Both COVID-19 exposure (ORadj. 1.4; CI 1.3–1.6) and FI (ORadj 3.2; CI 2.7–3.8) are independent and significant predictors of GAD. Thus, the impact of FI on GAD was considerably stronger than that of COVID-19 exposure. Conclusion: Persistent threats to survival play a substantial role for mental health, specifically GAD. High anxiety prevalence in the population requires programs to reduce violence and enhance social support. Even during a pandemic, addressing FI as a key driver of GAD should be prioritized by policymakers., Peer Reviewed