Sex-Specific Associations of Brain-Derived Neurotrophic Factor and Cardiorespiratory Fitness in the General Population

The brain-derived neurotrophic factor (BDNF) was initially considered to be neuron-specific. Meanwhile, this neurotrophin is peripherally also secreted by skeletal muscle cells and increases due to exercise. Whether BDNF is related to cardiorespiratory fitness (CRF) is currently unclear. We analyzed the association of serum BDNF levels with CRF in the general population (Study of Health in Pomerania (SHIP-TREND) from Northeast Germany; n = 1607, 51% female; median age 48 years). Sex-stratified linear regression models adjusted for age, height, smoking, body fat, lean mass, physical activity, and depression analyzed the association between BDNF and maximal oxygen consumption (VO2peak), maximal oxygen consumption normalized for body weight (VO2peak/kg), and oxygen consumption at the anaerobic threshold (VO2@AT). In women, 1mL/min higher VO2peak, VO2peak/kg, and VO2@AT were associated with a 2.43 pg/mL (95% confidence interval [CI]: 1.16 to 3.69 pg/mL; p = 0.0002), 150.66 pg/mL (95% CI: 63.42 to 237.90 pg/mL; p = 0.0007), and 2.68 pg/mL (95% CI: 0.5 to 4.8 pg/mL; p = 0.01) higher BDNF serum concentration, respectively. No significant associations were found in men. Further research is needed to understand the sex-specific association between CRF and BDNF. © 2019 by the authors. Licensee MDPI, Basel, Switzerland

Sex-Specific associations of brain-derived neurotrophic factor and cardiorespiratory fitness in the general population

The brain-derived neurotrophic factor (BDNF) was initially considered to be neuron-specific. Meanwhile, this neurotrophin is peripherally also secreted by skeletal muscle cells and increases due to exercise. Whether BDNF is related to cardiorespiratory fitness (CRF) is currently unclear. We analyzed the association of serum BDNF levels with CRF in the general population (Study of Health in Pomerania (SHIP-TREND) from Northeast Germany; n = 1607, 51% female; median age 48 years). Sex-stratified linear regression models adjusted for age, height, smoking, body fat, lean mass, physical activity, and depression analyzed the association between BDNF and maximal oxygen consumption (VO2peak), maximal oxygen consumption normalized for body weight (VO2peak/kg), and oxygen consumption at the anaerobic threshold (VO2@AT). In women, 1mL/min higher VO2peak, VO2peak/kg, and VO2@AT were associated with a 2.43 pg/mL (95% confidence interval [CI]: 1.16 to 3.69 pg/mL; p = 0.0002), 150.66 pg/mL (95% CI: 63.42 to 237.90 pg/mL; p = 0.0007), and 2.68 pg/mL (95% CI: 0.5 to 4.8 pg/mL; p = 0.01) higher BDNF serum concentration, respectively. No significant associations were found in men. Further research is needed to understand the sex-specific association between CRF and BDNF. © 2019 by the authors. Licensee MDPI, Basel, Switzerland

Vat Photopolymerization of Cemented Carbide Specimen

Numerous studies show that vat photopolymerization enables near-net-shape printing of ceramics and plastics with complex geometries. In this study, vat photopolymerization was investigated for cemented carbide specimens. Custom-developed photosensitive WC-12 Co (wt%) slurries were used for printing green bodies. The samples were examined for defects using quantitative microstructure analysis. A thermogravimetric analysis was performed to develop a debinding program for the green bodies. After sintering, the microstructure and surface roughness were evaluated. As mechanical parameters, Vickers hardness and Palmqvist fracture toughness were considered. A linear shrinkage of 26–27% was determined. The remaining porosity fraction was 9.0%. No free graphite formation, and almost no η-phase formation occurred. WC grain growth was observed. 76% of the WC grains measured were in the suitable size range for metal cutting tool applications. A hardness of 1157 HV10 and a Palmqvist fracture toughness of 12 [Formula: see text] was achieved. The achieved microstructure exhibits a high porosity fraction and local cracks. As a result, vat photopolymerization can become an alternative forming method for cemented carbide components if the amount of residual porosity and defects can be reduced

The impact of parental role distributions, work participation, and stress factors on family health-related outcomes: Study protocol of the prospective multi-method cohort "Dresden Study on Parenting, Work, and Mental Health" (DREAM)

The Dresden Study on Parenting, Work, and Mental Health (“DResdner Studie zu Elternschaft, Arbeit, und Mentaler Gesundheit”, DREAM) aims to prospectively investigate the relationship between parental work participation, role distribution, stress factors, and their effects on perinatal outcomes and long-term family mental and somatic health in a community sample targeting N = 4,000 individuals, i.e., 2,000 couples, expecting a child and residing in Dresden, Germany (interim sample of N = 1,410 participants, recruitment ongoing). Various questionnaires are completed at four measurement points from pregnancy to 2 years postpartum (prolongation into middle childhood planned). Applying a multi-method approach, long-term endocrinological data (analyses of hair cortisol concentrations and other endogenous hormones, “DREAMHAIR”) and qualitative interview data (regarding gender role attitudes and distribution of domestic work, child care, and paid employment; “DREAMTALK”) are obtained. In this study protocol, the theoretical background, methods, and preliminary results considering sociodemographic characteristics during pregnancy and birth-related factors at 8 weeks postpartum are presented. Additionally, there is a focus on our endocrinological sub-study DREAMHAIR. In this sub-study currently comprising N = 152 participants, i.e., 88 families (recruitment ongoing), we want to gain knowledge on the transgenerational processes of stress regulation and psychopathology in the whole family by analyzing hair cortisol concentrations in both parents and children during the course from pregnancy (or after birth regarding children) to at least 2 years postpartum. By comparing data of the community sample to a clinical sample of mothers with postpartum mental disorders, their children, and their partners during the period between admission and discharge from a mother-baby unit and post-treatment (“DREAMMBU”), the course of mothers' psychopathology, parent-infant interaction, and infant regulation disorders with special regard to long-term endocrine correlates will be examined. With previous studies neglecting the fathers or partners involved, a major advantage of DREAM is the use of a multi-method and multi-level approach by examining the whole family in a longitudinal design. Therefore, the DREAM study will contribute to a better understanding of the role of social, work, and stress factors for mental and somatic health and its long-term endocrine correlates in the natural course of becoming a family

Pulmonary magnetic resonance-guided online adaptive radiotherapy of locally advanced: the PUMA trial

Abstract Background Patients with locally-advanced non-small-cell lung cancer (LA-NSCLC) are often ineligible for surgery, so that definitive chemoradiotherapy (CRT) represents the treatment of choice. Nevertheless, long-term tumor control is often not achieved. Intensification of radiotherapy (RT) to improve locoregional tumor control is limited by the detrimental effect of higher radiation exposure of thoracic organs-at-risk (OAR). This narrow therapeutic ratio may be expanded by exploiting the advantages of magnetic resonance (MR) linear accelerators, mainly the online adaptation of the treatment plan to the current anatomy based on daily acquired MR images. However, MR-guidance is both labor-intensive and increases treatment times, which raises the question of its clinical feasibility to treat LA-NSCLC. Therefore, the PUMA trial was designed as a prospective, multicenter phase I trial to demonstrate the clinical feasibility of MR-guided online adaptive RT in LA-NSCLC. Methods Thirty patients with LA-NSCLC in stage III A-C will be accrued at three German university hospitals to receive MR-guided online adaptive RT at two different MR-linac systems (MRIdian Linac®, View Ray Inc. and Elekta Unity®, Elekta AB) with concurrent chemotherapy. Conventionally fractioned RT with isotoxic dose escalation up to 70 Gy is applied. Online plan adaptation is performed once weekly or in case of major anatomical changes. Patients are followed-up by thoracic CT- and MR-imaging for 24 months after treatment. The primary endpoint is twofold: (1) successfully completed online adapted fractions, (2) on-table time. Main secondary endpoints include adaptation frequency, toxicity, local tumor control, progression-free and overall survival. Discussion PUMA aims to demonstrate the clinical feasibility of MR-guided online adaptive RT of LA-NSCLC. If successful, PUMA will be followed by a clinical phase II trial that further investigates the clinical benefits of this approach. Moreover, PUMA is part of a large multidisciplinary project to develop MR-guidance techniques. Trial registration ClinicalTrials.gov: NCT05237453

Platelet PD-L1 reflects collective intratumoral PD-L1 expression and predicts immunotherapy response in non-small cell lung cancer

Immune-checkpoint inhibitors (ICI) have transformed oncological therapy. Up to 20% of all non-small cell lung cancers (NSCLCs) show durable responses upon treatment with ICI, however, robust markers to predict therapy response are missing. Here we show that blood platelets interact with lung cancer cells and that PD-L1 protein is transferred from tumor cells to platelets in a fibronectin 1, integrin α5β1 and GPIbα-dependent manner. Platelets from NSCLC patients are found to express PD-L1 and platelet PD-L1 possess the ability to inhibit CD4 and CD8 T-cells. An algorithm is developed to calculate the activation independent adjusted PD-L1 payload of platelets (pPD-L1(Adj.)), which is found to be superior in predicting the response towards ICI as compared to standard histological PD-L1 quantification on tumor biopsies. Our data suggest that platelet PD-L1 reflects the collective tumor PD-L1 expression, plays important roles in tumor immune evasion and overcomes limitations of histological quantification of often heterogeneous intratumoral PD-L1 expression