Introduction: The Heart Rate Performance Curve (HRPC) is neither linear nor uniform and related to ß1-adrenoceptor sensitivity. As aging and exercise influence ß1-adrenoceptors we suggested age, sex and performance effects on the HRPC. Aim of the study was to examine the effects of aging on the deflection of the HRPC in maximal incremental cycle ergometer exercise (CE) in a large cohort of healthy subjects. Methods: Heart rate (HR) data of 2,980 men (51 ± 15 years) and 1,944 women (52 ± 14 years) were classified into age groups (≤20 up to >80 years). We analyzed age and performance (P low 25%-quartile and P high 75%-quartile of age predicted power) effects on HR max and on the degree (k) and the type (regular downward deflection k > 0.1, linear −0.1 ≤ k ≤ 0.1 and atypical upward deflection k < −0.1) of the HRPC. Results: k-values decreased significantly with age in men and women and were significantly higher in women. Atypical HRPC's increased by a linear trend from ≤20 to 70 years (m) respectively 80 years (w) from 10 to 43% (m) and 9 to 30% (w). HR max of all age groups was lower in P low and overall number of atypical HRPC's was 21% (m) and 16% (w) higher compared to P high. Conclusion: Aging increased the number of atypical HRPC's with upward deflection in CE tests, which influences exercise intensity prescription especially when using fixed percentages of HR max. Changes in HRPC's were affected by sex and performance, where women generally and subjects with higher performance presented less atypical HRPC's even at older age.

Background: Obesity increases the risk of coronary heart disease, partly due to its strong association with atherogenic dyslipidemia, characterized by high triglycerides and low high-density lipoprotein (HDL) cholesterol levels. Functional impairment of HDL may contribute to the increased cardiovascular mortality, but the effect of obesity on composition, structure, and function of HDL is not well understood. Design and Methods: We determined HDL composition, HDL subclass distribution, parameters of HDL function, and activities of most important enzymes involved in lipoprotein remodeling, including lecithin–cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in relatively young normal weight (n = 26), overweight (n = 22), and obese (n = 20) women. Results: Obesity (body mass index (BMI) ≥ 30) was associated with noticeable changes in LCAT and CETP activities and altered HDL composition, such as decreased apolipoprotein A-I, cholesterol, and phospholipid content, while pro-inflammatory HDL serum amyloid a content was increased. We observed a marked shift towards smaller HDL subclasses in obesity linked to lower anti-oxidative capacity of serum. LCAT activity, HDL subclass distribution, and HDL-cholesterol were associated with soluble leptin receptor, adiponectin, and liver enzyme activities. Of note, most of these alterations were only seen in obese women but not in overweight women. Conclusions: Obesity markedly affects HDL metabolism, composition, and subclass distribution linked to changes in liver and adipose tissue. HDL dysfunction may contribute to increased cardiovascular risk in obesity.

Summary Background Anti‐TNF antibodies were the first biologic treatment option for patients with inflammatory bowel diseases. Aims To assess length of treatment persistence of first anti‐TNF therapy and influencing factors used in the standard care of patients with inflammatory bowel diseases. Methods Single‐centre, retrospective study from a register including patients who received anti‐TNF therapy in the last 20 years at the study centre. Kaplan‐Meier analysis with log‐rank test was used to describe treatment persistence. With multivariable Cox regression analysis, risk factors for treatment failure were investigated. Results Five hundred thirty‐eight patients (CD, Crohn's disease: 367, UC, ulcerative colitis: 147, inflammatory bowel disease unclassified: 24) with a median follow‐up of 8.1 years were included. Median (95% confidence interval) treatment persistence in the total cohort was 2.3 years (28 [22, 38] months), and nearly half of patients withdrew from treatment within 2 years. Male patients were treated longer than females (male: 37 [25, 48] months, female: 23 [14, 33] months, P = 0.002). Treatment persistence was longer in CD compared to UC (CD: 39 [30, 50] months, UC: 13 [9, 19] months, P < 0.001), and patients with CD remained longer on adalimumab than on infliximab treatment (adalimumab: 67 [55, 95] months, infliximab: 19 [14, 31] months, P < 0.001). Treatment failure (52%) and side effects (25%) were the most common reasons for withdrawal from therapy; 14% withdrew due to remission. Female sex was identified as independent predictor for treatment failure in UC (hazard ratio [CI]: 1.73 [1.02‐2.92], P = 0.04). Conclusion Long‐term treatment persistence of first anti‐TNF therapy was limited in patients with inflammatory bowel diseases, primarily due to treatment failure and side effects.

Glioblastoma (GBM) is an utterly devastating cerebral neoplasm and current therapies only marginally improve patients’ overall survival (OS). The PI3K/AKT/mTOR pathway participates in gliomagenesis through regulation of cell growth and proliferation. Since it is an upstream regulator of the rate-limiting translation initiation step of protein synthesis, controlled by eukaryotic initiation factors (eIFs), we aimed for a profound basic characterization of 17 eIFs to identify potential novel therapeutic targets for gliomas. Therefore, we retrospectively analyzed expressions of mTOR-related proteins and eIFs in human astrocytoma samples (WHO grades I–IV) and compared them to non-neoplastic cortical control brain tissue (CCBT) using immunoblot analyses and immunohistochemistry. We examined mRNA expression using qRT-PCR and additionally performed in silico analyses to observe the influence of eIFs on patients’ survival. Protein and mRNA expressions of eIF3B, eIF3I, eIF4A1, eIF4H, eIF5 and eIF6 were significantly increased in high grade gliomas compared to CCBT and partially in low grade gliomas. However, short OS was only associated with high eIF3I gene expression in low grade gliomas, but not in GBM. In GBM, high eIF4H gene expression significantly correlated with shorter patient survival. In conclusion, we identified eIF3I and eIF4H as the most promising targets for future therapy for glioma patients.

Consumer electronics returns are typically returned by the retailer to the manufacturer for a full refund of the wholesale price. This practice does not sufficiently motivate the retailer to reduce the volume of returns. Different mechanisms have been proposed to incentivize the retailer to reduce returns, such as a reduced wholesale price for returns below a target, but they do not consider the subsequent disposition of returns. The high value of returns usually justifies refurbishment and resale. We study how competition between refurbished returns sold by the manufacturer and new products sold at the retailer affects retailer behavior. We find that the retailer never exerts more effort to reduce returns when faced with competition through the online store. The manufacturer's profitability, however, is always higher with an online store. The online store is also preferable to a strategy where the manufacturer only partially refunds the retailer for returns.