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AbstractMany beneficial proprieties have been associated with polyphenols from green tea, such as chemopreventive, anticarcinogenic, antiatherogenic and antioxidant actions. In this study, we investigated the effects of green tea polyphenols (GTPs) and their principal catechins on the function of P-glycoprotein (P-gp), which is involved in the multidrug resistance phenotype of cancer cells. GTPs (30 μg/ml) inhibit the photolabeling of P-gp by 75% and increase the accumulation of rhodamine-123 (R-123) 3-fold in the multidrug-resistant cell line CHRC5, indicating that GTPs interact with P-gp and inhibit its transport activity. Moreover, the modulation of P-gp transport by GTPs was a reversible process. Among the catechins present in GTPs, EGCG, ECG and CG are responsible for inhibiting P-gp. In addition, EGCG potentiates the cytotoxicity of vinblastine (VBL) in CHRC5 cells. The inhibitory effect of EGCG on P-gp was also observed in human Caco-2 cells, which form an intestinal epithelial-like monolayer. Our results indicate that, in addition to their anti-cancer properties, GTPs and more particularly EGCG inhibit the binding and efflux of drugs by P-gp. Thus, GTPs or EGCG might be potential agents for modulating the bioavailability of P-gp substrates at the intestine and the multidrug resistance phenotype associated with expression of this transporter in cancer cells.

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.

In this study we used functional magnetic resonance imaging to investigate age-related changes in large-scale brain functional networks during memory encoding and recognition in 12 younger and 16 older adults. For each participant, functional brain networks were constructed by computing temporal correlation matrices of 90 brain regions and analyzed using graph theoretical approaches. We found the age-related changes mainly in the long-range connections with widespread reductions associated with aging in the fronto-temporal and temporo-parietal regions, and a few age-related increases in the posterior parietal regions. Graph theoretical analysis revealed that the older adults had longer path lengths linking different regions in the functional brain networks as compared to the younger adults. Further analysis indicated that the increases in shortest path length in the networks were combined with the loss of long-range connections. Finally, we showed that for older adults, frontal areas played reduced roles in the network (reduced regional centrality), whereas several default-mode regions played increased roles relative to younger subjects (increased regional centrality). Together, our results suggest that normal aging is associated with disruption of large-scale brain systems during the performance of memory tasks, which provides novel insights into the understanding of age-related decline in multiple cognitive functions.

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.

The World Health Organization has called on nation-states to statutorily govern, and integrate into state-funded healthcare systems, practitioners of traditional and complementary medicine (T&CM) (whose therapeutic approaches that fall outside the boundaries of conventional biomedicine). To date, however, there exist few rigorous reports of the degree to which individual nations have responded to this call. This study, an environmental scan, comprehensively documents the statutory governance and government reimbursement of T&CM practitioners in the United States (US). Across the US, where health practitioner governance falls within state and territorial (rather than federal) jurisdiction, over 300 laws have been enacted to statutorily regulate a wide range of T&CM practitioners. Nurse-midwives and chiropractors are universally licensed across all 56 US regulatory jurisdictions (50 states, 5 territories and the District of Columbia); other major T&CM practitioner groups are regulated in fewer jurisdictions (acupuncturists, n = 52; massage therapists, n = 50; direct-entry [non-nurse] midwives, n = 36; naturopaths, n = 24). Additional statutory stipulations exist to govern chiropractic assistants (n = 30), auricular (ear) acupuncture practitioners (n = 24), homeopathic practitioners (n = 3), and psychedelic facilitators (n = 1), as well as biomedical professionals who practice acupuncture and related techniques, e.g., ‘dry needling’ (n = 44). While professional entry requirements for licensed T&CM practitioners are substantially harmonized across jurisdictions, restricted titles and statutory scopes of practice vary. Ten states have furthermore implemented ‘safe harbor’ (‘negative licensing’) exemption laws enabling otherwise-unregulated T&CM practitioners to legally practice. Limited government reimbursement for T&CM care is available across several federal and state programs, including Medicare, Tricare, Veterans Health Authority, and Medicaid. Nurse-midwifery and chiropractic care is most frequently reimbursed; acupuncturists, naturopaths and massage therapists are eligible for much more limited coverage. Medicaid programs for low-income people in ten states furthermore cover the services of (unlicensed but statutorily-recognized) birth doulas. Additional research is needed to assess the impact of these regulations on US health 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.

It has been reported that the elderly use co-contraction of the tibialis anterior (TA) and plantarflexor muscles for longer duration during quiet standing than the young. However, the particular role of ankle muscle co-contractions in the elderly during quiet standing remains unclear. Therefore, the objective of this study was to investigate the association between ankle muscle co-contractions and postural steadiness during standing in the elderly. Twenty-seven young (27.2±4.5yrs) and twenty-three elderly (66.2±5.0yrs) subjects were asked to stand quietly on a force plate for five trials. The center of pressure (COP) trajectory and its velocity (COPv) as well as the center of mass (COM) trajectory and its velocity (COMv) and acceleration (ACC) were calculated using the force plate outputs. Electromyograms were obtained from the right TA, soleus (SOL), and medial gastrocnemius (MG) muscles. Periods of TA activity (TAon) and inactivity (TAoff) were determined using an EMG threshold based on TA resting level. Our results indicate that, in the elderly, the COPv, COMv, and ACC variability were significantly larger during TAon periods compared to TAoff periods. However, in the young, no significant association between respective variability and TA activity was found. We conclude that ankle muscle co-contractions in the elderly are not associated with an increase, but a decrease in postural steadiness. Future studies are needed to clarify the causal relationship between (1) ankle muscle co-contractions and (2) joint stiffness and multi-segmental actions during standing as well as their changes with aging.