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Human aging is associated with skeletal muscle atrophy and functional impairment (sarcopenia). Multiple lines of evidence suggest that mitochondrial dysfunction is a major contributor to sarcopenia. We evaluated whether healthy aging was associated with a transcriptional profile reflecting mitochondrial impairment and whether resistance exercise could reverse this signature to that approximating a younger physiological age. Skeletal muscle biopsies from healthy older (N = 25) and younger (N = 26) adult men and women were compared using gene expression profiling, and a subset of these were related to measurements of muscle strength. 14 of the older adults had muscle samples taken before and after a six-month resistance exercise-training program. Before exercise training, older adults were 59% weaker than younger, but after six months of training in older adults, strength improved significantly (P<0.001) such that they were only 38% lower than young adults. As a consequence of age, we found 596 genes differentially expressed using a false discovery rate cut-off of 5%. Prior to the exercise training, the transcriptome profile showed a dramatic enrichment of genes associated with mitochondrial function with age. However, following exercise training the transcriptional signature of aging was markedly reversed back to that of younger levels for most genes that were affected by both age and exercise. We conclude that healthy older adults show evidence of mitochondrial impairment and muscle weakness, but that this can be partially reversed at the phenotypic level, and substantially reversed at the transcriptome level, following six months of resistance exercise training.

We have derived values of the Ultraviolet Index (UVI) at solar noon using the Tropospheric Ultraviolet Model (TUV) driven by ozone, temperature and aerosol fields from climate simulations of the first phase of the Chemistry-Climate Model Initiative (CCMI-1). Since clouds remain one of the largest uncertainties in climate projections, we simulated only the clear-sky UVI. We compared the modelled UVI climatologies against present-day climatological values of UVI derived from both satellite data (the OMI-Aura OMUVBd product) and ground-based measurements (from the NDACC network). Depending on the region, relative differences between the UVI obtained from CCMI/TUV calculations and the ground-based measurements ranged between −5.9% and 10.6%. We then calculated the UVI evolution throughout the 21st century for the four Representative Concentration Pathways (RCPs 2.6, 4.5, 6.0 and 8.5). Compared to 1960s values, we found an average increase in the UVI in 2100 (of 2–4%) in the tropical belt (30°N-30°S). For the mid-latitudes, we observed a 1.8 to 3.4 % increase in the Southern Hemisphere for RCP 2.6, 4.5 and 6.0, and found a 2.3% decrease in RCP 8.5. Higher increases in UVI are projected in the Northern Hemisphere except for RCP 8.5. At high latitudes, ozone recovery is well identified and induces a complete return of mean UVI levels to 1960 values for RCP 8.5 in the Southern Hemisphere. In the Northern Hemisphere, UVI levels in 2100 are higher by 0.5 to 5.5% for RCP 2.6, 4.5 and 6.0 and they are lower by 7.9% for RCP 8.5. We analysed the impacts of greenhouse gases (GHGs) and ozone-depleting substances (ODSs) on UVI from 1960 by comparing CCMI sensitivity simulations (1960–2100) with fixed GHGs or ODSs at their respective 1960 levels. As expected with ODS fixed at their 1960 levels, there is no large decrease in ozone levels and consequently no sudden increase in UVI levels. With fixed GHG, we observed a delayed return of ozone to 1960 values, with a corresponding pattern of change observed on UVI, and looking at the UVI difference between 2090s values and 1960s values, we found an 8 % increase in the tropical belt during the summer of each hemisphere. Finally we show that, while in the Southern Hemisphere the UVI is mainly driven by total ozone column, in the Northern Hemisphere both total ozone column and aerosol optical depth drive UVI levels, with aerosol optical depth having twice as much influence on the UVI as total ozone column does.

Background Strategies such as Choosing Wisely have been established to identify the overuse of interventions considered as low-value. Reduction of low-value practices will require patients to understand why certain interventions are no longer recommended. The objective of this study was to determine whether older adults accept the rationale for and perceive themselves ready to de-adopt annual electrocardiogram testing, imaging for low back pain, the use of antibiotics for sinusitis, the use of sedative-hypnotics for insomnia, and the use of antipsychotics to treat behavioural symptoms of dementia. Methods A self-administered iPad survey was distributed to consecutive patients aged 50 years and older, presenting to three primary care outpatient practices in Ontario, Canada. Data from patients who were able and willing to complete the survey while waiting to see their physician were included. The survey queried knowledge, attitudes and behaviours around the targeted low-value interventions, before and after exposure to a Choosing Wisely Canada patient educational brochure on one of these five topics. A subset of patients agreed to participate in a semi-structured interview after their clinic visit. Results Three-hundred and forty-four patients (mean age 63, range 50–88, 59 % female) read the materials and completed the survey. Forty-eight percent (95 % CI 43–53 %) intended to discuss the information with a healthcare provider. Forty-five percent (95 % CI 40–51 %) expressed a desire to change current low-value practices. Approximately two-thirds of those who indicated they would not change future behaviours explained that it was because they were already espousing the Choosing Wisely values. After reading the Choosing Wisely brochures, knowledge improved independent of age, sex and education in 48 % (95 % CI 38–57 %) of participants about electrocardiogram testing, in 74 % (95 % CI 65–82 %) about use of antipsychotics, in 66 % (95 % CI 52–78 %) about use of antibiotics for sinusitis, in 60 % (95 % CI 46–72 %) about imaging for low back pain, and in 40 % (95 % CI 26–55 %) about sedative-hypnotic use in the elderly. Conclusions The majority of primary care patients seem ready to de-adopt low-value practices. Provision of education in clinic waiting rooms can help improve knowledge around unnecessary care.

Gap junction communication (GJC) mediated by connexins is critical for heart function. To gain insight into the causal relationship of molecular mechanisms of disease pathology, it is important to understand which mechanisms contribute to impairment of gap junctional communication. Here, we present an update on the known modulators of connexins, including various interaction partners, kinases, and signaling cascades. This gap junction network (GJN) can serve as a blueprint for data mining approaches exploring the growing number of publicly available data sets from experimental and clinical studies.

Abstract. In the context of epilepsy monitoring, electroencephalography (EEG) remains the modality of choice. Functional near-infrared spectroscopy (fNIRS) is a relatively innovative modality that cannot only characterize hemodynamic profiles of seizures but also allow for long-term recordings. We employ deep learning methods to investigate the benefits of integrating fNIRS measures for seizure detection. We designed a deep recurrent neural network with long short-term memory units and subsequently validated it using the CHBMIT scalp EEG database—a compendium of 896 h of surface EEG seizure recordings. After validating our network using EEG, fNIRS, and multimodal data comprising a corpus of 89 seizures from 40 refractory epileptic patients was used as model input to evaluate the integration of fNIRS measures. Following heuristic hyperparameter optimization, multimodal EEG-fNIRS data provide superior performance metrics (sensitivity and specificity of 89.7% and 95.5%, respectively) in a seizure detection task, with low generalization errors and loss. False detection rates are generally low, with 11.8% and 5.6% for EEG and multimodal data, respectively. Employing multimodal neuroimaging, particularly EEG-fNIRS, in epileptic patients, can enhance seizure detection performance. Furthermore, the neural network model proposed and characterized herein offers a promising framework for future multimodal investigations in seizure detection and prediction.

The transfection efficiency (TE) of chitosan–plasmid DNA (pDNA) polyplexes can be critically modulated by the polymer degree of deacetylation (DDA) and molecular weight (MW). This study was performed to test the hypothesis that the TE dependence on chitosan MW and DDA is related to the polyplex stability, hence their intracellular decondensation/unpacking kinetics. Major barriers to nonviral gene transfer were studied by image-based quantification. Although uptake increased with increased DDA, it did not appear to be a structure-dependent process affecting TE, nor was nuclear entry. Colocalization analysis showed that all chitosans trafficked through lysosomes with similar kinetics. Fluorescent resonant energy transfer (FRET) analysis revealed a distinct relationship between TE and polyplex dissociation rate. The most efficient chitosans showed an intermediate stability and a kinetics of dissociation, which occurred in synchrony with lysosomal escape. In contrast, a rapid dissociation before lysosomal escape was found for the inefficient low DDA chitosan whereas the highly stable and inefficient complex formed by a high MW and high DDA chitosan did not dissociate even after 24 hours. This study identified that the kinetics of decondensation in relation to lysosomal escape was a most critical structure-dependent process affecting the TE of chitosan polyplexes.

Aqueous L-selenomethionine (SeMet) embryo exposures represent a rapid and simplified method for investigating the embryotoxic effects of SeMet. Using zebrafish (Danio rerio) as a model organism, the objective of the present study was to characterize the effects of waterborne exposure to both SeMet and tert-butyl hydroperoxide (tBOOH) to early life stages of zebrafish pre-treated with the antioxidant tert-butyl hydroquinone (tBHQ) in an attempt to investigate the mechanism of Se toxicity as it relates to oxidative stress. During the initial concentration range finding experiment, recently fertilized embryos were exposed for five days to 5, 25, 125, and 625 µ g/L tBHQ pre-treatment. Survival, hatchability, time to hatch, the frequency and severity of deformities (total and type), and changes in the expression of seven antioxidant-associated genes were determined. Exposures to SeMet and tBOOH reduced hatchability, increased time to hatch, decreased survival, increased the incidence and severity of deformities, and increased glutathione-disulfide reductase (gsr) expression in the pre-treated tBOOH treatment group. g Se/L (as SeMet). These exposures informed the second experiment in which embryos were exposed to two concentrations of SeMet (25 and 125 µ g Se/L) and 75 mg/L tBOOH either with (tBOOH-t, 25-t, 125-t) or without (tBOOH, 25, 125) a 4 h 100 µ