Cigarette smoke extract exacerbates hyperpermeability of cerebral endothelial cells after oxygen glucose deprivation and reoxygenation

Cigarette smoking is a risk factor for stroke and is linked to stroke severity. Previous studies have shown that cigarette smoke extract (CSE) triggers endothelial dysfunction in vitro by initiating oxidative stress and/or an inflammatory response. In addition, cerebral endothelial dysfunction (particularly at the level of the blood-brain barrier [BBB]) contributes to stroke pathogenesis. Therefore, we hypothesized that cigarette smoking may influence stroke, at least in part, by exacerbating ischaemia-induced BBB disruption. To test this, we examined the effect of CSE on the permeability of cerebral endothelial cells exposed to oxygen glucose deprivation and reoxygenation (OGD + RO). We found that the loss of BBB integrity following ischaemic/reperfusion-like conditions was significantly worsened by CSE. Despite this being associated with increased mRNA expression of Nox catalytic subunits, reactive oxygen species (ROS) levels were however markedly lower. Furthermore, this occurred in association with elevated expression of antioxidant enzymes (SOD1, SOD2, and Gpx-1), suggesting an antioxidant defence response. Lastly, we found that CSE significantly upregulated mRNA expression of cytokines (IL-6 and TGF-β). Collectively, these results show that acute exposure to CSE worsens BBB disruption caused by OGD + RO, however, this is not linked to elevated ROS levels but may involve inflammatory mechanisms

A Randomized Controlled Trial of a Self‐Regulation Intervention for Older Adults with Asthma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98408/1/jgs12218.pd

Properties and biases of the global heat flow compilation

Geothermal heat flow is inferred from the gradient of temperature values in boreholes or short-penetration probe measurements. Such measurements are expensive and logistically challenging in remote locations and, therefore, often targeted to regions of economic interest. As a result, measurements are not distributed evenly. Some tectonic, geologic and even topographic settings are overrepresented in global heat flow compilations; other settings are underrepresented or completely missing. These limitations in representation have implications for empirical heat flow models that use catalogue data to assign heat flow by the similarity of observables. In this contribution, we analyse the sampling bias in the Global Heat Flow database of the International Heat Flow Commission; the most recent and extensive heat flow catalogue, and discuss the implications for accurate prediction and global appraisals. We also suggest correction weights to reduce the bias when the catalogue is used for empirical modelling. From comparison with auxiliary variables, we find that each of the following settings is highly overrepresented for heat flow measurements; continental crust, sedimentary rocks, volcanic rocks, and Phanerozoic regions with hydrocarbon exploration. Oceanic crust, cratons, and metamorphic rocks are underrepresented. The findings also suggest a general tendency to measure heat flow in areas where the values are elevated; however, this conclusion depends on which auxiliary variable is under consideration to determine the settings. We anticipate that using our correction weights to balance disproportional representation will improve empirical heat flow models for remote regions and assist in the ongoing assessment of the Global Heat Flow database

What promotes or prevents greater use of appropriate compression in people with venous leg ulcers? A qualitative interview study with nurses in the north of England using the Theoretical Domains Framework

OBJECTIVES: To investigate factors that promote and prevent the use of compression therapy in people with venous leg ulcers. DESIGN: Qualitative interview study with nurses using the Theoretical Domains Framework (TDF). SETTING: Three National Health Service Trusts in England. PARTICIPANTS: Purposive sample of 15 nurses delivering wound care. RESULTS: Nurses described factors which made provision of compression therapy challenging. Organisational barriers (TDF domains environmental context and resources/knowledge, skills/behavioural regulation) included heavy/increasing caseloads; lack of knowledge/skills and the provision of training; and prescribing issues (variations in bandaging systems/whether nurses could prescribe). Absence of specialist leg ulcer services to refer patients into was perceived as a barrier to providing optimal care by some community-based nurses. Compression use was perceived to be facilitated by clinics for timely initial assessment; continuity of staff and good liaison between vascular/leg ulcer clinics and community teams; clear local policies and care pathways; and opportunities for training such as ‘shadowing’ in vascular/leg ulcer clinics. Patient engagement barriers (TDF domains goals/beliefs about consequences) focused on getting patients ‘on board’ with compression, and supporting them in using it. Clear explanations were seen as key in promoting compression use. CONCLUSIONS: Rising workload pressures present significant challenges to enhancing leg ulcer services. There may be opportunities to develop facilitated approaches to enable community nursing teams to make changes to practice, enhancing quality of patient care. The majority of venous leg ulcers could be managed in the community without referral to specialist community services if issues relating to workloads/skills/training are addressed. Barriers to promoting compression use could also be targeted, for example, through the development of clear patient information leaflets. While the patient engagement barriers may be easier/quicker to address than organisational barriers, unless organisational barriers are addressed it seems unlikely that all people who would benefit from compression therapy will receive it

Diverse outcomes of CO2 fixation using alkali metal amides including formation of a heterobimetallic lithium-sodium carbamato-anhydride via lithium-sodium bis-hexamethyldisilazide

Fixation of CO2 by lithium amides derived from pyrrole and diisopropylamine generates a lithium carbamate polymer and dodecamer respectively. Moving to lithium-sodium hexamethyldisilazide produces a more complicated, intriguing reaction, where unusually the bimetallic composition is maintained in the product but its composition contains both carbamato and anhydride functionalities

Functional status predicts acute care readmissions from inpatient rehabilitation in the stroke population

Objective: Acute care readmission risk is an increasingly recognized problem that has garnered significant attention, yet the reasons for acute care readmission in the inpatient rehabilitation population are complex and likely multifactorial. Information on both medical comorbidities and functional status is routinely collected for stroke patients participating in inpatient rehabilitation. We sought to determine whether functional status is a more robust predictor of acute care readmissions in the inpatient rehabilitation stroke population compared with medical comorbidities using a large, administrative data set. Methods: A retrospective analysis of data from the Uniform Data System for Medical Rehabilitation from the years 2002 to 2011 was performed examining stroke patients admitted to inpatient rehabilitation facilities. A Basic Model for predicting acute care readmission risk based on age and functional status was compared with models incorporating functional status and medical comorbidities (Basic-Plus) or models including age and medical comorbidities alone (Age-Comorbidity). C-statistics were compared to evaluate model performance. Findings: There were a total of 803,124 patients: 88,187 (11%) patients were transferred back to an acute hospital: 22,247 (2.8%) within 3 days, 43,481 (5.4%) within 7 days, and 85,431 (10.6%) within 30 days. The C-statistics for the Basic Model were 0.701, 0.672, and 0.682 at days 3, 7, and 30 respectively. As compared to the Basic Model, the best-performing Basic-Plus model was the Basic+Elixhauser model with C-statistics differences of +0.011, +0.011, and + 0.012, and the best-performing Age-Comorbidity model was the Age+Elixhauser model with C-statistic differences of -0.124, -0.098, and -0.098 at days 3, 7, and 30 respectively. Conclusions: Readmission models for the inpatient rehabilitation stroke population based on functional status and age showed better predictive ability than models based on medical comorbidities

A Lagerstätte from Australia provides insight into the nature of Miocene mesic ecosystems

Reduced precipitation in the Miocene triggered the geographic contraction of rainforest ecosystems around the world. In Australia, this change was particularly pronounced; mesic rainforest ecosystems that once dominated the landscape transformed into the shrublands, grasslands, and deserts of today. A lack of well-preserved fossils has made it difficult to understand the nature of Australian ecosystems before the aridification. Here, we report on an exceptionally well-preserved rainforest biota from New South Wales, Australia. This Konservat-Lagerstätte hosts a rich diversity of microfossils, plants, insects, spiders, and vertebrate remains preserved in goethite. We document evidence for several species interactions including predation, parasitism, and pollination. The fossils are indicative of an oxbow lake in a mesic rainforest and suggest that rainforest distributions have shifted since the Miocene. The variety of fossils preserved, together with high fidelity of preservation, allows for unprecedented insights into the mesic ecosystems that dominated Australia during the Miocene

Structural studies of donor-free and donor-solvated sodium carboxylates

Focusing mainly on sodium 2-ethylhexanoate, this study reveals that the carboxylate exists as a dimer in MeOD solution as evidenced by Diffusion Ordered NMR SpectroscopY (DOSY). Two crystalline varieties with distinct polymeric structures have been synthesised and crystallographically characterised. A mixed 1,10-phenanthroline–water solvate [{(C5H10)(C2H5)COONa.(H2O)[1,10-phen]}2]∞ contains dimeric [Na(OH)2]2 subunits, which propagate through hydrogen bonds between O atoms of the carboxylate and OH water bonds. Adjacent polymeric chains interdigitate with each other through π-π interactions between 1,10-phen rings. Solvent-free sodium 2-ethylhexanoate has five-coordinate cations comprising one bidentate chelating and three monodentate carboxylate oxygen atoms. Here, the packing arrangement is different with the central hydrophilic (NaO2)∞ core surrounded by a wrapping of disordered alkyl groups. A similar polymeric structure is observed for the crystalline DMSO-solvated sodium valproate [{(C3H7)(C4H8)COONa.(DMSO)}]∞. This adopts a layered arrangement comprising alternating sodium carboxylate hydrophilic layers and hydrophobic organic bilayers

Adjuvant enzalutamide for the treatment of early-stage androgen-receptor positive, triple-negative breast cancer: a feasibility study.

PURPOSE: Chemotherapy with or without immunotherapy remains the mainstay of treatment for triple-negative breast cancer (TNBC). A subset of TNBCs express the androgen receptor (AR), representing a potential new therapeutic target. This study assessed the feasibility of adjuvant enzalutamide, an AR antagonist, in early-stage, AR-positive (AR +) TNBC. METHODS: This study was a single-arm, open-label, multicenter trial in which patients with stage I-III, AR ≥ 1% TNBC who had completed standard-of-care therapy were treated with enzalutamide 160 mg/day orally for 1 year. The primary objective of this study was to evaluate the feasibility of 1 year of adjuvant enzalutamide, defined as the treatment discontinuation rate of enzalutamide due to toxicity, withdrawal of consent, or other events related to tolerability. Secondary endpoints included disease-free survival (DFS), overall survival (OS), safety, and genomic features of recurrent tumors. RESULTS: Fifty patients were enrolled in this study. Thirty-five patients completed 1 year of therapy, thereby meeting the prespecified trial endpoint for feasibility. Thirty-two patients elected to continue with an optional second year of treatment. Grade ≥ 3 treatment-related adverse events were uncommon. The 1-year, 2-year, and 3-year DFS were 94%, 92% , and 80%, respectively. Median OS has not been reached. CONCLUSION: This clinical trial demonstrates that adjuvant enzalutamide is a feasible and well-tolerated regimen in patients with an early-stage AR + TNBC. Randomized trials in the metastatic setting may inform patient selection through biomarker development; longer follow-up is needed to determine the effect of anti-androgens on DFS and OS in this patient population