Neuroprotection and acidosis induced by cortical spreading depression

We read with interest the article “Cortical spreading depression produces a neuroprotective effect activating mitochondrial uncoupling protein-5” published in Neuropsychiatr Dis Treat by Viggiano et al.1 The authors showed that cerebral spreading depression (CSD) triggered uncoupling protein-5 (UCP-5),1 which had been reported to exert a long-term effect upon neuron protection.2 The result is another piece in CSD literature on modifying gene expressions to provide neuroprotection to subsequent ischemic episodes.3,

Complete head cerebral sensitivity mapping for diffuse correlation spectroscopy using subject-specific magnetic resonance imaging models

We characterize cerebral sensitivity across the entire adult human head for diffuse correlation spectroscopy, an optical technique increasingly used for bedside cerebral perfusion monitoring. Sixteen subject-specific magnetic resonance imaging-derived head models were used to identify high sensitivity regions by running Monte Carlo light propagation simulations at over eight hundred uniformly distributed locations on the head. Significant spatial variations in cerebral sensitivity, consistent across subjects, were found. We also identified correlates of such differences suitable for real-time assessment. These variations can be largely attributed to changes in extracerebral thickness and should be taken into account to optimize probe placement in experimental settings

Bioluminescence Imaging of Heme Oxygenase-1 Upregulation in the Gua Sha Procedure

Gua Sha is a traditional Chinese folk therapy that employs skin scraping to cause subcutaneous microvascular blood extravasation and bruises. The protocol for bioluminescent optical imaging of HO-1-luciferase transgenic mice reported in this manuscript provides a rapid in vivo assay of the upregulation of the heme oxygenase-1 (HO-1) gene expression in response to the Gua Sha procedure. HO-1 has long been known to provide cytoprotection against oxidative stress. The upregulation of HO-1, assessed by the bioluminescence output, is thought to represent an antioxidative response to circulating hemoglobin products released by Gua Sha. Gua Sha was administered by repeated strokes of a smooth spoon edge over lubricated skin on the back or other targeted body part of the transgenic mouse until petechiae (splinter hemorrhages) or ecchymosis (bruises) indicative of extravasation of blood from subcutaneous capillaries was observed. After Gua Sha, bioluminescence imaging sessions were carried out daily for several days to follow the dynamics of HO-1 expression in multiple internal organs

The Effect of Swimming Goggles on Intraocular Pressure and Blood Flow within the Optic Nerve Head

Purpose: Goggles are frequently worn in the sport of swimming and are designed to form a seal around the periorbital tissue orbit. The resultant pressure on the eye may have the potential to affect intraocular pressure and blood flow of the optic nerve head. This study evaluates the influence of wearing swimming goggles on intraocular pressure (IOP) and blood flow of the ocular nerve head (ONH) in normal subjects. Materials and Methods: Thirty healthy participants took part in this study. The IOP of each participant was measured using a Goldmann tonometer. Measurements were taken immediately before putting on swimming goggles, at 5, 10, 30, and 60 minutes after putting on swimming goggles, and then immediately after taking off the goggles. Blood flow of the ONH was measured using the Heidelberg retinal flowmeter. Results: The average IOP before, during and after wearing the swimming goggles were 11.88 ± 2.82 mmHg, 14.20 ± 2.81 mmHg and 11.78 ± 2.89 mmHg, respectively. The IOP increased immediately after putting on the goggles (p < 0.05) and then returned to normal values immediately after removal (p> 0.05). Blood flow of the ONH was 336.60 ± 89.07 Arbitrary Units (AU) before and 319.18 ± 96.02 AU after the goggles were worn (p < 0.05). Conclusion: A small but significant IOP elevation was observed immediately after the swimming goggles were put on. This elevated IOP was maintained while the goggles were kept on, and then returned to normal levels as soon as they were taken off. Blood flow of the ONH did not change significantly throughout the experiment. These facts should be considered for safety concerns, especially in advanced glaucoma patients

Acupuncture mobilizes the brain's default mode and its anti-correlated network in healthy subjects

Previous work has shown that acupuncture stimulation evokes deactivation of a limbic-paralimbic-neocortical network (LPNN) as well as activation of somatosensory brain regions. This study explores the activity and functional connectivity of these regions during acupuncture vs. tactile stimulation and vs. acupuncture associated with inadvertent sharp pain. Acupuncture during 201 scans and tactile stimulation during 74 scans for comparison at acupoints LI4, ST36 and LV3 was monitored with fMRI and psychophysical response in 48 healthy subjects. Clusters of deactivated regions in the medial prefrontal, medial parietal and medial temporal lobes as well as activated regions in the sensorimotor and a few paralimbic structures can be identified during acupuncture by general linear model analysis and seed-based cross correlation analysis. Importantly, these clusters showed virtual identity with the default mode network and the anti-correlated task-positive network in response to stimulation. In addition, the amygdala and hypothalamus, structures not routinely reported in the default mode literature, were frequently involved in acupuncture. When acupuncture induced sharp pain, the deactivation was attenuated or became activated instead. Tactile stimulation induced greater activation of the somatosensory regions but less extensive deactivation of the LPNN. These results indicate that the deactivation of the LPNN during acupuncture cannot be completely explained by the demand of attention that is commonly proposed in the default mode literature. Our results suggest that acupuncture mobilizes the anti-correlated functional networks of the brain to mediate its actions, and that the effect is dependent on the psychophysical response

Mindfulness Awareness Is Associated With a Lower Risk of Anxiety and Depressive Symptoms in Older Adults With Neurocognitive Disorders

Background: Apart from depressive disorders, there are great interests in adopting mindfulness based interventions (MBIs) for other mental health conditions. Depression and anxiety are common in people with neurocognitive disorders (NCD). The potential of MBIs as an adjuvant treatment in this cognitively at-risk group should be further explored. Objectives: The current study explored the association between depression and anxiety symptoms with dispositional mindfulness in older adults, and if same association stays in the context of cognitive impairment. Methods: The Hong Kong Mental Morbidity Survey for Older People (MMSOP) is an ongoing epidemiology study of the prevalence of neurocognitive and mental disorders in adults aged 60 years or over in Hong Kong. MMSOP evaluated cognitive function, psychiatric symptoms (Clinical Interview Schedule-revised, CIS-R), chronic physical disease burden, psychosocial support, and resilience factors, including dispositional mindfulness as measured by the Mindful Attention Awareness Scale (MAAS). We analyzed the impact of MAAS on CIS-R and potential moderation effects of mindfulness. Results: In March 2021, 1,218 community dwelling participants completed assessments. The mean age of the sample is 69.0 (SD 6.9) years. Eight hundred and two participants (65.7%) were not demented (CDR 0) and 391 (32%) and 25 (2%) were categorized as having mild NCD (CDR 0.5) and major NCD (CDR 1 or more), respectively. One hundred forty-three (11.7%) satisfied ICD-10 criteria for anxiety or depressive disorder as measured by CIS-R. Linear regression analysis showed that female gender, CIRS, and MAAS scores were significant factors associated with CIS-R scores. MAAS scores moderated and attenuated the impact CIRS on CIS-R (adjusted R2 = 0.447, p < 0.001). MAAS scores remained as significant moderator for CIRS in patients with NCD (CDR ≥ 0.5) (adjusted R2 = 0.33, p < 0.001). Conclusion: Interim findings of the MMSOP suggested that dispositional mindfulness is associated with lower level of mood symptoms in community dwelling older adults in Hong Kong. The interaction effects further suggested that high mindful awareness may reduce the adverse effects of chronic physical morbidity on mental health. The observation stayed in the participants with cognitive impairment. We should further explore MBIs as a non-pharmacological treatment for in older adults at-risk of physical morbidity and cognitive decline

Probiotic and Oxytocin Combination Therapy in Patients with Autism Spectrum Disorder: A Randomized, Double-Blinded, Placebo-Controlled Pilot Trial

Autism spectrum disorder (ASD) is a rapidly growing neurodevelopmental disorder. Both probiotics and oxytocin were reported to have therapeutic potential; however, the combination therapy has not yet been studied. We conducted a randomized, double-blinded, placebo-controlled, 2-stage pilot trial in 35 individuals with ASD aged 3-20 years (median = 10.30 years). Subjects were randomly assigned to receive daily Lactobacillus plantarum PS128 probiotic (6 × 1010 CFUs) or a placebo for 28 weeks; starting on week 16, both groups received oxytocin. The primary outcomes measure socio-behavioral severity using the Social Responsiveness Scale (SRS) and Aberrant Behavior Checklist (ABC). The secondary outcomes include measures of the Clinical Global Impression (CGI) scale, fecal microbiome, blood serum inflammatory markers, and oxytocin. All outcomes were compared between the two groups at baseline, 16 weeks, and 28 weeks into treatment. We observed improvements in ABC and SRS scores and significant improvements in CGI-improvement between those receiving probiotics and oxytocin combination therapy compared to those receiving placebo (p < 0.05). A significant number of favorable gut microbiome network hubs were also identified after combination therapy (p < 0.05). The favorable social cognition response of the combination regimen is highly correlated with the abundance of the Eubacterium hallii group. Our findings suggest synergic effects between probiotics PS128 and oxytocin in ASD patients, although further investigation is warranted

Global prevalence and genotype distribution of hepatitis C virus infection in 2015 : A modelling study

Publisher Copyright: © 2017 Elsevier LtdBackground The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding John C Martin Foundation.publishersversionPeer reviewe

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701