No abstract

Viral protein U (VpU) of HIV-1 plays an important role in downregulation of the main HIV-1 receptor CD4 from the surface of infected cells. Physical binding of VpU to newly synthesized CD4 in the endoplasmic reticulum is an early step in a pathway leading to proteasomal degradation of CD4. In this study, regions in the cytoplasmic domain of VpU involved in CD4 binding were identified by NMR spectroscopy. Amino acids in both helices found in the cytoplasmic region of VpU in membrane-mimicking detergent micelles experience chemical shift perturbations upon binding to CD4, whereas amino acids between the two helices and at the C-terminus of VpU show no or only small changes, respectively. The topology of the complex was further studied with paramagnetic relaxation enhancement. Paramagnetic spin labels were attached at three sequence positions of a CD4 peptide comprising the transmembrane and cytosolic domains of the receptor. VpU binds to a membrane-proximal region in the cytoplasmic domain of CD4. Structured digital abstractVpU and CD4 bind by nuclear magnetic resonance (View interaction)

Purpose The aim of this study was to estimate the prevalence of pain, the extent of analgesics intake and the mental health status of German pre-hospital emergency medical service (EMS) personnel. Methods We conducted a nationwide online survey, which consisted of sociodemographic and job-related items, questions on pain and analgesics intake and the short-version of the validated Depression–Anxiety–Stress Scale (DASS-21). Results A total of 774 EMS personnel with a mean age of 33.03 (standard error [SE] 0.37) years were included into the final analysis of which 23.77% were female. Pain was reported by 58.64% (454 of 774) of the study participants with 10.72% (95% confidence interval [CI] 8.54%; 13.29%) suffering from chronic, 1.68% (95% CI 0.89%; 2.87%) from acute and 46.25% (95% CI 41.49%; 51.30%) from recurrent pain, respectively. Most frequent location of pain was lumbar spine. Analgesics were used by 52.76% (239 of 454) of pre-hospital EMS personnel with pain (acute 76.92% / chronic 69.88% / recurrent 47.90%). Moreover, participants with chronic and recurrent pain indicated significantly higher depression (p ≤ 0.001), anxiety (p ≤ 0.001), and stress (p ≤ 0.001) levels compared to those without pain, respectively. Conclusion This study indicates a high prevalence of pain and analgesics usage in participating German pre-hospital EMS personnel and a poorer mental health in those with chronic and recurrent pain. Therefore, disease prevention and health promotion measures are needed to preserve health of pre-hospital EMS personnel.

Purpose In osteoporosis, prior fracture is a strong predictor of subsequent fracture. This study aimed to assess the imminent risk of subsequent fracture following an initial fracture in osteoporosis patients in Germany, and to identify clinical and demographic characteristics that are independently associated with subsequent fracture risk. Methods In this retrospective, observational cohort study using German real-world claims data, male and female patients aged ≥ 50 years with osteoporosis who experienced an initial (“index”) hip/femur, vertebral, forearm/wrist/hand or shoulder/upper arm fracture between 2010 and 2014 were included. The incidence and timing of subsequent fractures during a 1-year follow-up period were analyzed. Independent risk factors for subsequent fracture were identified by multivariate regression analysis. Results A total of 18,354 patients (mean age: 77 years; standard deviation: 9.8) were included. Of these, 2918 (15.9%) suffered a subsequent fracture during the 1-year follow-up period. The incidence of subsequent fracture was higher following an index vertebral fracture (18.0%) than after an index forearm/wrist/hand fracture (14.1%) or index hip/femur fracture (12.1%). Subsequent 1-year fracture incidence was generally higher in older patients. Index fracture type, age, epilepsy/use of antiepileptics, and heart failure were all independently associated with subsequent fracture risk. Conclusion Osteoporosis patients in Germany are at imminent risk of subsequent fracture during the first year following an initial fracture. They should be targeted for immediate post-fracture treatment to reduce the risk of further fractures, especially in the presence of specific risk factors such as old age or index vertebral fracture.