Symptomatic intracranial arterial stenosis (SIAS) is very common in octo-and nonagenarians, especially in the Chinese population, and is likely the most common cause of stroke recurrence worldwide. Clinical trials demonstrate that endovascular treatment, such as stenting, may not be suitable for octogenarians with systemic diseases. Hence, less invasive methods for the octogenarian patients are urgently needed. Our previous study (unique identifier: NCT01321749) showed that repetitive bilateral arm ischemic preconditioning (BAIPC) reduced the incidence of stroke recurrence by improving cerebral perfusion (confirmed by single photon emission computed tomography and transcranial Doppler sonography) in patients younger than 80 years of age; however, the safety and effectiveness of BAIPC on stroke prevention in octo-and nonagenarians with SIAS are still unclear. The objective of this study was to evaluate the safety and effectiveness of BAIPC in reducing stroke recurrence in octo-and nonagenarian patients with SIAS. Fifty-eight patients with SIAS were enrolled in this randomized controlled prospective study for 180 consecutive days. All patients enrolled in the study received standard medical management. Patients in the BAIPC group (n=30) underwent 5 cycles consisting of bilateral arm ischemia followed by reperfusion for 5 min each twice daily. Those in the control group (n=28) underwent sham-BAIPC twice daily. Blood pressure, heart rate, local skin status, plasma myoglobin, and plasma levels of thrombotic and inflammatory markers were documented in both groups before beginning the study and for the first 30 days. Finally, the incidences of stroke recurrence and magnetic resonance imaging during the 180 days of treatment were compared. Compared with the control, BAIPC had no adverse effects on blood pressure, heart rate, local skin integrity, or plasma myoglobin, and did not induce cerebral hemorrhage in the studied cohort. BAIPC reduced plasma high sensitive C-reactive protein, interleukin-6, plasminogen activator inhibitor-1, leukocyte count, and platelet aggregation rate and elevated plasma tissue plasminogen activator (all p<0.01). In 180 days, 2 infarctions and 7 transient ischemic attacks were observed in the BAIPC group compared with 8 infarctions and 11 transient ischemic attacks in the sham BAIPC group (p<0.05). BAIPC may safely inhibit stroke recurrence, protect against brain ischemia, and ameliorate plasma biomarkers of inflammation and coagulation in octo-and nonagenarians with SIAS. A multicenter trial is ongoing.Clinical Trial Registration: www.clinicaltrials.gov, unique identifier: NCT01570231.

Introduction: Integrated knowledge regarding pre-exposure prophylaxis (PrEP) awareness and willingness to use PrEP can be useful for HIV prevention in high incidence groups. This review summarizes the awareness of PrEP and willingness to use PrEP among men who have sex with men (MSM). Methods: Online electronic databases were searched before 31 August 2021. A meta-analysis was conducted to pool studies analysing PrEP awareness and willingness to use PrEP. LOESS regression and linear regression were applied to fit the trends over time for the proportion of MSM aware of PrEP and willing to use PrEP. Dose-response meta-analysis (DRMA) was conducted by a restricted cubic spline model to explore the relationship between willingness to use PrEP and selected factors. Results and Discussion: A total of 156 articles involving 228,403 MSM were included. The pooled proportions of MSM aware of PrEP and willing to use PrEP were 50.0 (95% CI: 44.8-55.2) and 58.6% (95% CI: 54.8-62.4), respectively. PrEP awareness varied among countries with different economic status and different WHO regions, among different publication and research years, PrEP types and support policies. PrEP willingness differed among countries with different economic status and groups with different risks of HIV. The awareness of PrEP increased from 2007 to 2019 with a slope of 0.040260 (p<0.0001), while the proportion of MSM willing to use PrEP decreased from 2007 to 2014 (slope = -0.03647, p = 0.00390) but increased after 2014 (slope = 0.04187, p = 0.03895). The main facilitators of willingness to use PrEP were PrEP awareness, condomless sexual behaviours, high perceived risk of HIV infection and influence of social network. The main barriers were doubts about the efficacy and side effects of PrEP. DRMA results indicated that MSM with more sexual partners and lower level of education were more willing to use PrEP. No publication bias was observed. Conclusions: The proportions of PrEP awareness and willingness to use PrEP among MSM have increased since 2014, although the awareness was low and the willingness was moderate. Improving awareness of PrEP through increasing access to PrEP-related health education and enhancing risk perceptions of HIV infection could have positive effects on the willingness to use PrEP among MSM.

Aims This study investigated the safety and efficacy of remote ischemic conditioning (RIC) on ameliorating the sequelae of ischemic moyamoya disease (iMMD). Methods A total of 30 iMMD patients underwent long‐term RIC and were followed up at 0.5, 1, and 2 years for clinical outcomes, including frequency of stroke recurrence, Patient Global Impression of Change (PGIC) scale, peak systolic velocities (PSV), and cerebral perfusion. Results During the whole RIC treatment process, no RIC‐related adverse event occurred. Only one of 30 patients suffered a onetime infarction (3.3%), and the ratios of acceptable PGIC were 88.2%, 64.3%, and 92.3% at 0.5, 1, and 2 years follow‐up. Kaplan‐Meier analysis showed the frequency of stroke recurrence was significantly reduced after RIC (P = .013). The frequency of TIA per week was 1.1 (0.6, 2.8) prior to RIC and 0.1 (0.0, 0.5) post‐RIC (P < .01). Compared to baseline, PSV values were significantly reduced after RIC treatment (P = .002 at 0.5, P = .331 at 1, and P = .006 at 2 years). In patients undergoing perfusion studies, 75% obtained improvement on followed‐up SPECT and 95% on followed‐up PET maps. Conclusions Remote ischemic conditioning may be beneficial on controlling iMMD‐induced ischemic events, relieving symptoms, and improving cerebral perfusion, without incidence of complications in this case series.

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Hypoxic preconditioning (HPC) elicits resistance to more drastic subsequent insults, which potentially provide neuroprotective therapeutic strategy, but the underlying mechanisms remain to be fully elucidated. Here, we examined the effects of HPC on synaptic ultrastructure in olfactory bulb of mice. Mice underwent up to five cycles of repeated HPC treatments, and hypoxic tolerance was assessed with a standard gasp reflex assay. As expected, HPC induced an increase in tolerance time. To assess synaptic responses, Western blots were used to quantify protein levels of representative markers for glia, neuron, and synapse, and transmission electron microscopy was used to examine synaptic ultrastructure and mitochondrial density. HPC did not significantly alter the protein levels of astroglial marker (GFAP), neuron-specific markers (GAP43, Tuj-1, and OMP), synaptic number markers (synaptophysin and SNAP25) or the percentage of excitatory synapses versus inhibitory synapses. However, HPC significantly affected synaptic curvature and the percentage of synapses with presynaptic mitochondria, which showed concomitant change pattern. These findings demonstrate that HPC is associated with changes in synaptic ultrastructure.

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BackgroundThe aim of this study was to compare the use of the standard 12-lead electrocardiogram (ECG) with the SAN-Atrial-AVN-His (SAAH) ECG (Model PHS-A10), a new automated and integrated signals recognition system that detects micro-waveforms within the P, QRS, and T-wave, in a pig model of acute myocardial infarction (MI).Material/MethodsSix medium-sized domestic Chinese pigs underwent general anesthesia, and an angioplasty balloon was placed and dilated for 120 minutes in the first diagonal coronary artery arising from the left anterior descending (LAD) coronary artery. A standard ECG and a SAAH ECG (Model PHS-A10) were used to evaluate: 1) the number of wavelets in ST-T segment in lead V5; 2) the duration of the repolarization initial (Ri), or duration of the wavelets starting from the J-point to the endpoint of the wavelets in the ST interval; 3) the duration of the repolarization terminal (Rt), of the wavelets, starting from the endpoint of the wavelets in the ST interval to the cross-point of the T-wave and baseline; 4) the ratio Ri: Rt.ResultsFollowing coronary artery occlusion, duration of Ri and Ri/Rt increased, and Rt decreased, which was detected by the SAAH ECG (Model PHS-A10) within 12 seconds, compared with standard ECG that detected ST segment depression at 24 seconds following coronary artery occlusion.ConclusionsThe findings from this preliminary study in a pig model of acute MI support the need for clinical studies to evaluate the SAAH ECG (Model PHS-A10) for the early detection of acute MI.