Electroacupuncture pretreatment attenuates cerebral ischemic injury through α7 nicotinic acetylcholine receptor-mediated inhibition of high-mobility group box 1 release in rats

<p>Abstract</p> <p>Background</p> <p>We have previously reported that electroacupuncture (EA) pretreatment induced tolerance against cerebral ischemic injury, but the mechanisms underlying this effect of EA are unknown. In this study, we assessed the effect of EA pretreatment on the expression of α7 nicotinic acetylcholine receptors (α7nAChR), using the ischemia-reperfusion model of focal cerebral ischemia in rats. Further, we investigated the role of high mobility group box 1 (HMGB1) in neuroprotection mediated by the α7nAChR and EA.</p> <p>Methods</p> <p>Rats were treated with EA at the acupoint "Baihui (GV 20)" 24 h before focal cerebral ischemia which was induced for 120 min by middle cerebral artery occlusion. Neurobehavioral scores, infarction volumes, neuronal apoptosis, and HMGB1 levels were evaluated after reperfusion. The α7nAChR agonist PHA-543613 and the antagonist α-bungarotoxin (α-BGT) were used to investigate the role of the α7nAChR in mediating neuroprotective effects. The roles of the α7nAChR and HMGB1 release in neuroprotection were further tested in neuronal cultures exposed to oxygen and glucose deprivation (OGD).</p> <p>Results</p> <p>Our results showed that the expression of α7nAChR was significantly decreased after reperfusion. EA pretreatment prevented the reduction in neuronal expression of α7nAChR after reperfusion in the ischemic penumbra. Pretreatment with PHA-543613 afforded neuroprotective effects against ischemic damage. Moreover, EA pretreatment reduced infarct volume, improved neurological outcome, inhibited neuronal apoptosis and HMGB1 release following reperfusion, and the beneficial effects were attenuated by α-BGT. The HMGB1 levels in plasma and the penumbral brain tissue were correlated with the number of apoptotic neurons in the ischemic penumbra. Furthermore, OGD in cultured neurons triggered HMGB1 release into the culture medium, and this effect was efficiently suppressed by PHA-543,613. Pretreatment with α-BGT reversed the inhibitory effect of PHA-543,613 on HMGB1 release.</p> <p>Conclusion</p> <p>These data demonstrate that EA pretreatment strongly protects the brain against transient cerebral ischemic injury, and inhibits HMGB1 release through α7nAChR activation in rats. These findings suggest the novel potential for stroke interventions harnessing the anti-inflammatory effects of α7nAChR activation, through acupuncture or pharmacological strategies.</p

Avoidable costs of physical treatments for chronic back, neck and shoulder pain within the Spanish National Health Service: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Back, neck and shoulder pain are the most common causes of occupational disability. They reduce health-related quality of life and have a significant economic impact. Many different forms of physical treatment are routinely used. The objective of this study was to estimate the cost of physical treatments which, despite the absence of evidence supporting their effectiveness, were used between 2004 and 2007 for chronic and non-specific neck pain (NP), back pain (BP) and shoulder pain (SP), within the Spanish National Health Service in the Canary Islands (SNHSCI).</p> <p>Methods</p> <p>Chronic patients referred from the SNHSCI to private physical therapy centres for NP, BP or SP, between 2004 and 2007, were identified. The cost of providing physical therapies to these patients was estimated. Systematic reviews (SRs) and clinical practice guidelines (CPGs) for NP, BP and SP available in the same period were searched for and rated according to the Oxman and AGREE criteria, respectively. Those rated positively for ≥70% of the criteria, were used to categorise physical therapies as Effective; Ineffective; Inconclusive; and Insufficiently Assessed. The main outcome was the cost of physical therapies included in each of these categories.</p> <p>Results</p> <p>8,308 chronic cases of NP, 4,693 of BP and 5,035 of SP, were included in this study. Among prescribed treatments, 39.88% were considered Effective (physical exercise and manual therapy with mobilization); 23.06% Ineffective; 13.38% Inconclusive, and 23.66% Insufficiently Assessed. The total cost of treatments was € 5,107,720. Effective therapies accounted for € 2,069,932.</p> <p>Conclusions</p> <p>Sixty percent of the resources allocated by the SNHSCI to fund physical treatment for NP, BP and SP in private practices are spent on forms of treatment proven to be ineffective, or for which there is no evidence of effectiveness.</p

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

DAQ platform based on SoC-FPGA for high resolution time stamping in cosmic ray detection

Accurate timing in cosmic ray detection is critical for reconstruction of events from multiple scattered detectors. Since most of the detectors dedicated to study cosmic rays generate continuous analog signals, a precise timing depends on the sampling rate and the subsequent triggering system operating on the generated digital data stream. In this paper, a data acquisition platform based on a fully programmable System-On-Chip (SoC) and a high-speed analog to digital converter, able to manage 8-bit data resolution, 500MHz sampling rate and GPS connection for data synchronization is presented. The SoC is a ZYNQ 7000 device with a Field Programmable Gate Array (FPGA) and a dual core ARM processor embedded on a single chip. The system achieves 2 ns time resolution and is also able to increase data amplitude resolution through oversampling and can simultaneously generate a real time histogram of the incoming data. The platform has an embedded high voltage power supply control with temperature and pressure compensation for optimal and stable operation of different detectors. While the time critical activities are handled and carried out by the FPGA, software running on the dual core ARM processor with a real time operating system (FreeRTOS) provides Ethernet connection for remote control of the platform