Associations Between Multidimensional Sleep Health Parameters and Adolescents' Self-reported Light Exposure in the Free-living Environment.

The objective of this study was to characterize the associations between light exposure in the free-living environment and multiple dimensions of sleep health of typically developing adolescents. Fifty-six (29 girls, 27 boys) typically developing adolescents (mean age = 13.59, SD = 0.89, range = 12-17 years) participated. For six consecutive nights, sleep was assessed in the home environment using actigraphy. During the same period, participants were asked to fill out a daily sleep log and a daily light exposure log, and to complete questionnaires regarding their alertness and subjective sleep satisfaction. Longer self-reported exposure to daylight in the morning was associated with longer objectively measured sleep duration. Longer self-reported exposures to electronic devices in the evening were associated with later objectively measured sleep onset and offset times, shorter sleep duration, and greater day-to-day sleep variability. Longer morning exposure to outdoor light was associated with a longer sleep duration. Self-reported light exposure was not associated with sleep satisfaction, alertness/sleepiness, or sleep efficiency. Among the covariates, circadian preference accounted for the highest percentage of variance. Adolescents' sleep health is associated with the self-reported duration of exposure to daylight in the morning and to electronic devices in the evening.

[Evidence-Based Treatment and Differential Diagnoses of Olecranon Bursitis]. / Evidenz-basierte Behandlung und Differenzialdiagnostik der Bursitis olecrani.

Evidence-Based Treatment and Differential Diagnoses of Olecranon Bursitis Abstract. Bursitis olecrani is a common clinical diagnosis that can have systemic, infectious and traumatic causes. In this article we want to present the diagnostics, possible differential diagnoses, complications and the current therapy recommendations as a practical guide.

[Pain after Shoulder Prosthesis Is Not Always Due to Infection or Loosening]. / Schmerz nach Schulterprothese ­ nicht immer Infekt oder Lockerung.

Pain after Shoulder Prosthesis Is Not Always Due to Infection or Loosening Abstract. Summary: Suprascapular nerve neuropathy is becoming increasingly recognized as a reason for persistent shoulder pain. The underlying cause may be iatrogenic, as in the case of our patient, or due to ganglionic compression or traction. Unfortunately, diagnosis and thus adequate therapy is frequently delayed. With this case study, we would like to bring the neuropathy of the suprascapular nerve into focus for the general practice.

Evaluation of Microfluidic Ceiling Designs for the Capture of Circulating Tumor Cells on a Microarray Platform.

The capture of circulating tumor cells (CTCs) is still a challenging application for microfluidic chips, as these cells are rare and hidden in a huge background of blood cells. Here, different microfluidic ceiling designs in regard to their capture efficiency for CTCs in model experiments and more realistic conditions of blood samples spiked with a clinically relevant amount of tumor cells are evaluated. An optimized design for the capture platform that allows highly efficient recovery of CTCs from size-based pre-enriched samples under realistic conditions is obtained. Furthermore, the viability of captured tumor cells as well as single cell recovery for downstream genomic analysis is demonstrated. Additionally, the authors' findings underline the importance of evaluating rational design rules for microfluidic devices based on theoretical models by application-specific experiments.

Handling of informed consent and patient inclusion in research with geriatric trauma patients - a matter of protection or disrespect?

BACKGROUND: Despite the aging of numerous societies and future health care challenges, clinical research in the elderly is underrepresented. The aim of this review was to analyze the current practice exemplary in gerontotraumatology and to discuss potential improvements. MATERIALS AND METHODS: A literature review was performed in 2016 based on a PubMed search for gerontotraumatologic studies published between 2005 and 2015. Trials were evaluated for methodology and ethical and age-related aspects. RESULTS: The search revealed 649 articles, 183 of which met the inclusion criteria. The age range for inclusion was heterogeneous; one-third of trials included patients <65 years and only 11% excluded very elderly. Seventy-four trials excluded patients with typical comorbidities, with 55% of these without stating scientific reasons. Frailty was assessed in 94 trials and defined as the exclusion criterion in 66 of them. Informed consent (IC) was reportedly obtained in 144 trials; descriptions of the IC process mostly remained vague. Substitute decision making was described in 19 trials; the consenting party remained unclear in 45 articles. Diagnosed dementia was a primary exclusion criterion in 31% of the trials. Seventeen trials assessed decisional capacity before inclusion, with six using specific assessments. CONCLUSION: Many trials in gerontotraumatology exclude relevant subgroups of patients, and thus risk presenting biased estimates of the relevant treatment effects. Exclusion based on age, cognitive impairment, or other exhaustive exclusion criteria impedes specific scientific progress in the treatment of elderly patients. Meaningful trials could profit from a staged, transparent approach that fosters shared decision making. Rethinking current policies is indispensable to improve treatment and care of elderly trauma patients and to protect study participants and researchers alike.

G2-checkpoint targeting and radiosensitization of HPV/p16-positive HNSCC cells through the inhibition of Chk1 and Wee1.

BACKGROUND AND PURPOSE: HPV-positive HNSCC cells are characterized by radiosensitivity, inefficient DNA double-strand break repair and a profound and prolonged arrest in G2. Here we explored the effect of clinically relevant inhibitors of Chk1 and Wee1 to inhibit the radiation-induced G2-arrest in order to achieve further radiosensitization. MATERIAL AND METHODS: Assessment of Chk1 activity by Western blot; assessment of cell cycle distribution by propidium iodide staining and flow cytometry; assessment of cell survival by colony formation assay. HPV+ HNSCC cell lines: UD-SCC-2, UM-SCC-47 and UPCI-SCC-154; Chk1 inhibitors: LY2603618, MK8776; Wee1 inhibitor: AZD1775. RESULTS: Specific Chk1 inhibitors efficiently abrogated the radiation-induced G2-arrest and caused radiosensitization. Wee-inhibition by AZD1775 resulted in the activation of Chk1. This feedback mechanism is likely to counteract some of the effects of Wee1 inhibition but could be antagonized through the combined inhibition of both kinases. Combined inhibition was effective using profoundly reduced concentrations of both inhibitors and resulted in more efficient radiosensitization of the HPV-positive cell lines compared to p53 proficient normal human fibroblasts. CONCLUSIONS: Specific Chk1 inhibitors as well as the combined inhibition of Chk1 and Wee1 radiosensitize HPV-positive HNSCC cells.

Predicting oral absorption of drugs: a case study with a novel class of antimicrobial agents.

PURPOSE: The purpose of this work was to evaluate an oral absorption prediction model, maximum absorbable dose (MAD), which predicts a theoretical dose of drug that could be absorbed across rat intestine based on consideration of intestinal permeability, solute solubility, intestinal volume, and residence time. METHODS: In the present study, Caco-2 cell permeability, as a surrogate for rat intestinal permeability, and aqueous solubility were measured for 27 oxazolidinones. The oxazolidinones are a novel class of potential antibacterial agents currently under investigation. These values were used to estimate MAD for each of the compounds. Finally, these predicted values were compared to previously measured bioavailability data in the rat in order to estimate oral absorption properties. RESULTS: A reasonably good correlation between predicted dose absorbed and bioavailability was observed for most of the compounds. In a few cases involving relatively insoluble compounds, absorption was underestimated. For these compounds while aqueous solubility was low. solubility in 5% polysorbate 80 was significantly higher, a solvent possibly more representative of the small intestinal lumen. CONCLUSIONS: These results suggest that MAD may be useful for prioritizing early discovery candidates with respect to oral absorption potential. In the case of compounds with poor aqueous solubility, additional factors may have to be considered such as solubility in the intestinal lumen.

Pharmacokinetics and efficacy of linezolid in a gerbil model of Streptococcus pneumoniae-induced acute otitis media.

The oxazolidinone linezolid represents a new antibacterial class of potential benefit in managing multidrug-resistant gram-positive infections, including those caused by Streptococcus pneumoniae. In a gerbil model of acute otitis media (AOM) induced by either penicillin-resistant S. pneumoniae (PRSP; amoxicillin MIC = 8 micro g/ml, linezolid MIC = 1 micro g/ml) or penicillin-susceptible S. pneumoniae (PSSP; amoxicillin MIC = 0.015 micro g/ml, linezolid MIC = 1 micro g/ml), we explored the plasma and ear fluid levels of linezolid required to demonstrate efficacy. Threshold pathogen doses required to induce bilateral AOM (1,500 CFU/ear with PRSP; 30 CFU/ear with PSSP) were administered to gerbils by intrabullar injection on day 0. At peak infection ( approximately 10(6) to 10(7) CFU/ear flush; day 2 for PRSP-AOM and day 3 for PSSP-AOM), twice-a-day oral doses of linezolid, amoxicillin, or vehicle were administered over 4.5 days prior to collection and assay of middle ear effluents for S. pneumoniae content. Linezolid doses of >/=10 mg/kg of body weight induced significant cure rates of >/=72% versus both PRSP and PSSP infections, whereas amoxicillin at MIC of >/=42%, a C(max)/MIC ratio of >/=3.1, and a (24-h area under the curve)/MIC ratio of >/=30 h. Application of this model will be useful in defining preclinical pharmacodynamic relationships of novel antibiotics necessary to cure S. pneumoniae-induced AOM.