Cortical delta-opioid receptors potentiate K+ homeostasis during anoxia and oxygen-glucose deprivation.

Central neurons are extremely vulnerable to hypoxic/ischemic insult, which is a major cause of neurologic morbidity and mortality as a consequence of neuronal dysfunction and death. Our recent work has shown that delta-opioid receptor (DOR) is neuroprotective against hypoxic and excitotoxic stress, although the underlying mechanisms remain unclear. Because hypoxia/ischemia disrupts ionic homeostasis with an increase in extracellular K(+), which plays a role in neuronal death, we asked whether DOR activation preserves K(+) homeostasis during hypoxic/ischemic stress. To test this hypothesis, extracellular recordings with K(+)-sensitive microelectrodes were performed in mouse cortical slices under anoxia or oxygen-glucose deprivation (OGD). The main findings in this study are that (1) DOR activation with [D-Ala(2), D-Leu(5)]-enkephalinamide attenuated the anoxia- and OGD-induced increase in extracellular K(+) and decrease in DC potential in cortical slices; (2) DOR inhibition with naltrindole, a DOR antagonist, completely abolished the DOR-mediated prevention of increase in extracellular K(+) and decrease in DC potential; (3) inhibition of protein kinase A (PKA) with N-(2-[p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide dihydrochloride had no effect on the DOR protection; and (4) inhibition of protein kinase C (PKC) with chelerythrine chloride reduced the DOR protection, whereas the PKC activator (phorbol 12-myristate 13-acetate) mimicked the effect of DOR activation on K(+) homeostasis. These data suggest that activation of DOR protects the cortex against anoxia- or ODG-induced derangement of potassium homeostasis, and this protection occurs via a PKC-dependent and PKA-independent pathway. We conclude that an important aspect of DOR-mediated neuroprotection is its early action against derangement of K(+) homeostasis during anoxia or ischemia.     

Quality of life in long term ventilated adult patients with Duchenne muscular dystrophy

The aim of this study was to evaluate quality of life (QoL) and its possible determinants in patients affected by Duchenne muscular dystrophy (DMD) in late stages of their disease, when non-invasive ventilation (NIV) is already established. Forty-eight DMD patients who were treated by NIV were enrolled. QoL was assessed by the Individualized Neuromuscular Quality of Life (INQoL) questionnaire. By this questionnaire, different aspects of QoL were assessed on a scale from 0 (best) to 100 (worst). In addition, motor and respiratory function tests were performed. Dysautonomia symptoms, sleep quality, sleepiness, anxiety, and depression were evaluated by validated questionnaires. The global INQoL score was 42.8 ± 19, reflecting a moderately altered QoL. The physical health domain was heavily impaired while the psychosocial domain was only mildly affected. Independence had the highest scores (81.1 ± 21.2), proving to be the most affected item. On multivariate analysis, maximal inspiratory pressure and Pittsburgh Sleep Quality Index, but not daily duration of NIV therapy, predicted global INQoL score. Respiratory impairment and sleep quality were independent predictors of poor QoL in DMD patients under NIV. Sleep quality in DMD is often disregarded, while it should be carefully addressed to ensure a better QoL.     

miR‐137 inhibits proliferation of melanoma cells by targeting PAK2

MicroRNAs (miRNA) are key players in a variety of cancers including malignant melanoma. miR‐137 has been reported to be a tumor suppressor in melanoma and several targets have been identified for this miRNA. We previously developed a novel proteomics technology, ³⁵S in vivo/vitro labelling analysis for dynamic proteomics (SiLAD). Because of its high sensitivity in analysing protein expression rates, SiLAD has the potential to unravel miRNA effects on mRNAs coding for proteins with long half‐lives or high abundance. Using SiLAD, we discovered that miR‐137 significantly downregulated the expression rate of p21‐activated kinase 2 (PAK2) in melanoma cells. Bioinformatics analysis predicted PAK2 as a direct target of miR‐137, which was confirmed by luciferase reporter assay and Western blot analysis. We found that overexpression of miR‐137 inhibited the proliferation of melanoma cells, which could be phenocopied by knockdown of PAK2 using siRNAs. Furthermore, overexpression of PAK2 restored miR‐137‐mediated suppression of cell proliferation. These findings indicate that miR‐137 could inhibit proliferation through targeting PAK2 in melanoma cells.     

Evaluation of the psychometric properties of the social isolation measure (SIM) in adults with hearing loss

Objective: This study aimed to evaluate the psychometric properties of a brief, hearing-specific outcome measure: the Social Isolation Measure (SIM).

Design: In Phase 1, adults with hearing loss were invited to complete an online survey that contained the SIM, a hearing-specific participation questionnaire, a generic activity and participation questionnaire, and a generic loneliness questionnaire. In Phase 2, the participants were asked to complete the SIM for a second time 2–3 weeks following Phase 1.

Study Sample: One hundred and sixteen adults with hearing loss completed Phase 1. Ninety-five participants also completed Phase 2. Twenty-nine participants were excluded from the Phase 2 data analysis because they reported that their hearing had changed since Phase 1 or because they completed Phase 2 outside of the 2–3?week interval following Phase 1.

Results: In support of its construct validity, the SIM had a strong correlation with the hearing-specific questionnaire and moderate correlations with the generic questionnaires. The findings also supported the internal consistency, interpretability and test-retest reliability of the SIM.

Conclusions: The SIM was found to have strong psychometric properties. It could serve as a brief measure of perceived social isolation in research or clinical practice.     

Effect of temperature and atmosphere on the conductivity and electrochemical capacitance of single-unit-thick ruthenium dioxide

Wrapping a monoparticulate layer of 2–3-nm RuO₂ around the fibers comprising porous SiO₂ filter paper produces a conductive nanoshell in which ∼90% of the RuO₂ units are surface-sited, creating the equivalent of a supported single-unit layer of the oxide. The room temperature electronic conductivity, normalized for the dimensions of the total RuO₂(SiO₂) object, increases with calcination temperature reaching a maximum of 830 mS cm⁻¹ for a 200 °C-calcined paper, and then sharply decreases at higher temperatures as the nanoparticles in the ultrathin RuO₂ shell ripen and disrupt the connectivity. The calcination temperature also influences the electrochemical capacitance, which is optimized at 150 °C with a RuO₂-normalized specific capacitance of 850 F g⁻¹. Calcining the RuO₂(SiO₂) papers to temperatures ?250 °C reduces the electrochemical capacitance due to structural ordering and ripening of the RuO₂ nanoparticles composing the coating. The electrochemical capacitance and the magnitude of the electronic conductivity of the RuO₂(SiO₂) paper are unaffected by exposure to air, humidified air, Ar, humidified Ar, or methanol-saturated Ar at 25 °C. Exposing the papers at room temperature to either pure H₂ or humidified H₂ significantly reduces the pseudocapacitance and electronic conductivity. X-ray photoelectron spectroscopy confirms reduction of the RuO₂ to Ru and scanning electron microscopy demonstrates shrinkage-induced stress cracking and disruption of the H₂-reacted nanoscale coating. These results indicate that the RuO₂(SiO₂) architecture can serve as a rugged, inexpensive, and conductive gas-diffusion scaffold for the design of a carbon- and ionomer-free anode for direct methanol fuel cells.     

Effects of alcohol on disinhibition towards alcohol-related cues

BackgroundWe investigated (1) the effects of acute alcohol on inhibition of alcohol-related versus neutral cues, (2) the effects of drinking status on inhibition of alcohol-related versus neutral cues, and (3) the similarity of any effects of alcohol or drinking status across two different cue types (lexical versus pictorial).MethodsParticipants received 0.0 g/kg, 0.4 g/kg or 0.6 g/kg of alcohol in a between-subjects design. Healthy, heavy and light social alcohol users (n = 96) completed both lexical and pictorial cue versions of an alcohol-shifting task. Participants were instructed to respond to target stimuli by pressing the spacebar, but to ignore distracter stimuli. Errors towards distracter stimuli were analysed using a series of mixed-model ANOVAs, with between-subjects factors of challenge and drinking status and within-subjects factors of distracter type (alcohol, neutral) and block (shift, non-shift).ResultsLexical commission error data indicated a main effect of distracter (F [1,90] = 43.25, p < 0.001, η² = 0.33), which was qualified by a marginal interaction with challenge condition (F [2,90] = 2.77, p = 0.068, η² = 0.06). Following an acute high dose of alcohol participants made more errors towards alcohol distracters. Pictorial commission error data indicated a significant main effect of distracter (F [1,90] = 67.40, p < 0.001, η² = 0.43), such that all participants made more errors towards neutral image distracters versus alcohol distracter images.ConclusionsOur results reveal acute alcohol's impairment of inhibitory control may be enhanced when a response towards alcohol-related lexical stimuli is required to be withheld.     

Comparison of one versus two bronchodilators in ventilated COPD patients

Objective To compare the bronchodilating effect of a single drug, ipratropium bromide (IBr), with that of its combination with fenoterol (IBr+F).Design The study was triple blind and randomized.Setting Medical-surgical intensive care unit.Patients 12 patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation for severe respiratory failure.Interventions Before administering each drug, peak airway pressure (Ppeak), end inspiratory pressure (Pei), resistive pressure (Pres), and auto positive — end expiratory pressure (auto-PEEP) were measured. Inspiratory system resistance (Rins) and dynamic respiratory system compliance (C) were calculated. Arterial pH and blood gas determinations were made. These measurements were repeated 60 min after administration of each therapeutic regimen. For ipratropium bromide alone the dose was 0.04 mg. When the combination of drugs was used, the doses were 0.04 mg for ipratropium bromide and 0.1 mg for fenoterol.Measurements and results With the combination of both drugs, all the pressures in the airway, as well as the auto-PEEP and the Rins were significantly reduced (p<0.05) with respect to baseline values. With ipratropium bromide alone, no significant changes were observed either in the pressures or in the inspiratory resistance. No significant changes were observed either in the pH or blood gases with any of the treatments. The combination of both drugs produced significantly reduction in Pei and auto-PEEP when compared with ipratropium bromide alone.Conclusions The combination of both drugs is more effective than ipratropium bromide alone at the doses used in this study.