Risultati per: Nelle donne lo stress danneggia la salute dell’intestino

Introduction
Emergency service workers are routinely exposed to stress and trauma, and there is a need to address mental health symptoms early to prevent chronic impairment and/or psychiatric disorder. Digital health innovations mean that face-to-face psychosocial interventions can now be delivered remotely, which is particularly appealing to populations who have strong preferences for digital delivery, such as emergency service workers. This two phase study aims to first adapt the Skills fOr Life Adjustment and Resilience (SOLAR) programme into a smartphone application (‘app’), and then evaluate the effectiveness of this new app.
Methods and analyses
First, focus groups and codesign activities with mental health professionals and emergency service workers will be conducted to develop and test the prototype smartphone version of SOLAR (ie, SOLAR-m). Second, a multicentre randomised controlled trial will investigate the effectiveness of the new app, compared with an active control app, in reducing symptoms of anxiety and depression (primary outcome), as well as other indicators of mental health and work performance. Firefighters from one of the largest urban fire and rescue services in Australia who are currently experiencing distress will be invited to participate. After screening and baseline assessment, 240 will be randomised to receive either SOLAR-m or the control app for 5 weeks, with measurements pre, post and 3-month follow-up. Analyses will be conducted within an intention-to-treat framework using mixed modelling.

Ethics and dissemination
The current trial has received ethics approval from the University of Melbourne Human Research Ethics Committee (2021-20632-18826-5). Study results will be disseminated through peer-reviewed journals and conferences, with a focus on how to expand the new app to other trauma-affected populations if proven effective.

Trial registration number
ANZCTRN12621001141831.

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Objective
This study intended to assess the impact of COVID-19 pandemic on anxiety and stress among healthcare professionals in Ethiopia.

Design
This study applied a design of systematic review and meta-analysis of observational studies.

Data sources

Eligibility criteria and outcomes
Observational studies examining anxiety and stress among healthcare professionals in Ethiopia following COVID-19 pandemic were considered. The primary outcomes were the prevalence of anxiety and stress and the secondary outcomes were factors associated to the prevalence of anxiety and stress.

Data extraction and synthesis
Two authors extracted the data and performed quality assessment independently. The Newcastle-Ottawa Scale was used to evaluate the quality of eligible studies. Random-effect model with the inverse variance method was used to estimate the pooled effect size of the outcome variables with its 95% CI. Publication bias was checked by DOI plot and Luis Furuya Kanamori index. Stata V.14.0 (StataCorp) software was used for statistical analysis.

Results
Thirteen studies were included. From eight studies the pooled prevalence of anxiety was 46% (95% CI 0.30% to 0.61%, 2=0.0497, I2=99.07%, p

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This technology could improve exercise testing and ambulatory monitoring.

Stroke, Volume 54, Issue Suppl_1, Page ATP237-ATP237, February 1, 2023. Microglial activation & the failure of the antioxidant defense mechanisms are major hallmarks in different central nervous system injuries, mainly ischemic & hemorrhagic strokes. Cofilin is a cytoskeleton-associated protein involved in actin binding & severing. In our previous studies, we identified the potential role of cofilin in mediating microglial activation & neuronal apoptosis in ischemic & hemorrhagic conditions. Others have highlighted the involvement of cofilin in ROS production & the resultant neuronal death; however, more studies are needed to delineate the role of cofilin in oxidative stress conditions. Hence, the present study is aimed to investigate the role of cofilin in hydrogen peroxide (H2O2)-induced microglial activation & oxidative neuronal injury & its protection using a first-in-class small-molecule inhibitor of cofilin (SZ-3). An in vitro H2O2-induced cell death model was used in two different types of cells, human neuroblastoma (SH-SY5Y) & microglial (HMC3) cell lines. Cell viability was assessed by the Cell Counting Kit-8 assay. Western blotting was used to measure the expression levels of several proteins. Our results show that treatment with H2O2increases the expression of cofilin & slingshot-1 (SSH-1), an upstream regulator of cofilin, in microglial cells, which was significantly reduced in the SZ3 treated group. Cofilin inhibition significantly attenuated H2O2-induced microglial activation by reducing the release of proinflammatory mediators (HMGB1, TNF-α). Furthermore, we demonstrate that SZ3 protects against H2O2-induced cytotoxicity in SH-SY5Y cells & activates the AKT signaling pathway by increasing its phosphorylation levels. SZ3 treatment also induces the expression of Nrf2, a major transcription factor that regulates the oxidative stress response, & its related antioxidant enzymes (HO-1, SOD2, NQO1) in the SY-SY5Y cell. Together, these results suggest that cofilin inhibition plays an essential role in protecting neuronal cells under H2O2-induced oxidative stress, possibly by activating the antioxidant defense mechanisms & reducing microglial activation.

Stroke, Volume 54, Issue Suppl_1, Page AWMP6-AWMP6, February 1, 2023. Introduction:Hyperglycemia has consistently been associated with worse outcome following an acute ischemic stroke (AIS). Recent studies have shown that a stress glucose ratio (SGR) may be a better predictor of critical illness than absolute hyperglycemia. An elevated initial stress glucose ratio (iSGR) was significantly associated with malignant cerebral edema and ICH after thrombectomy. We sought to identify genetic loci related to iSGR in a cohort of the GENISIS (Genetics of Early Neurological InStability after Ischemic Stroke) study.Methods:GENISIS is a multi-site international study that enrolled AIS patients within 6 hours of symptom onset. A sub-cohort with available initial glucose and HbA1c levels was selected. For all patients, Hg38 imputed genotypes were available. iSGR was calculated by dividing initial glucose by the estimated average glucose concentration (= 28.7 * A1c – 46.7) and normalized by log transformation for the GWAS. Association was adjusted by age, sex, baseline NIHSS, principal components and genotyping rounds. Samples were analyzed by country of origin and ethnicity using Plink2 and then meta-analyzed by ethnicity using METAL.Results:Three separate populations were identified (African-Americans n=299; European-Americans n=622; and Spanish n=625). Median age was 71 (IQR 60-80) with 46% female. Baseline NIHSS was 11 (IQR 5-16). A suggestive loci (chr13:rs9560146, p=9.88×10-8) was identified in the meta-analysis. Gene-based analyses suggested that the loci in chromosome 13 is driven byKLF5(p=0.002). In addition, rs9560146 is also associated withKLF5gene expression in brain (eQTL p=3.30×10-3; frontal cortex: Braineac).Conclusions:We demonstrated that a variant inKLF5may be associated with iSGR in a cohort of AIS patients.KLF5is induced under hypoxia conditions and interacts with HIF-1a to mediate glucose homeostasis. Recently, a pre-clinical study demonstrated that a micro RNA (miR-10b-3p) had neuroprotective effects against ischemia/reperfusion injury by targeting KLF5. Thus, investigating the genetic architecture of stress hyperglycemia may be informative and reveal variants, genes or pathways involved in ischemic brain injury. We plan to recruit a cohort for replication and sample size expansion.

Stroke, Volume 54, Issue Suppl_1, Page AWP61-AWP61, February 1, 2023. Introduction:After an ischemic stroke or transient ischemic attack (TIA), patients may have post-event anxiety and re-experience transient neurological symptoms. However, some stroke patients develop persistent and disabling symptoms of post-traumatic stress disorder (PTSD). Data on post-stroke post-traumatic stress disorder (PS-PTSD) is sparse.Methods:We conducted a single-center observational pilot study of 20 adult patients diagnosed with stroke or TIA in the previous 31 days to 1 year. Patients completed the PTSD Check List-5 (PCL-5), Patient Health Questionnaire-9 (PHQ-9), stroke specific Quality of Life Scale-12 (SS-QOL-12), modified Rankin Scale of disability, and the National Institutes of Health Stroke Scale. The PCL-5 is a 20 item self-report score assessing symptoms of re-experiencing (Criterion B), avoidance (Criterion C), negative alterations in cognition or mood (Criterion D), and hyperarousal (Criterion E). Subjects were classified as having PS-PTSD with PCL-5 score ≥33 or endorsement of moderate symptoms in at least one B item, one C item, two D items, and two E items.Results:Twenty patients completed the PCL-5 and 19 completed the follow up scales. Seven patients (35%) were found to have PS-PTSD. Higher PCL-5 scores were significantly correlated with lower SS-QOL12 scores indicating worsened quality of life (r= -0.709, P=.001) and higher PHQ9 scores representing more depressive symptoms (r= 0.727, P

Stroke, Volume 54, Issue Suppl_1, Page ATMP32-ATMP32, February 1, 2023. Introduction:CD38 enzymatic activity is the main determinant of the age-dependent decline in nicotinamide adenine dinucleotide (NAD+) levels and the loss of CD38 function has been associated with increased longevity in rodents. Therefore, we hypothesize that the loss of CD38 and its enzymatic function will improve cognitive performance in advanced age through the preservation of NAD+levels and the protection against oxidative stress.Methods:CD38 Knockout (CD38KO) and C57BL/6J (wild type WT) male mice were aged for at least 24 months. The cognitive performance was compared through Barnes maze, Fear conditioning and Y-maze tests. Dihydroethidium (DHE), Diaminofluorescein-2 diacetate (DAF) and nicotinamide adenine dinucleotide phosphate NAD(P)H staining were used to assess the levels of superoxide, nitric oxide (NO) and NAD(P)H in the brain, respectively.Results:5 WT and 5 CD38KO mice aged (24-30) months were included. While there were no significant differences in fear conditioning and Y-maze tests, CD38KO mice showed better memory performance in Barnes maze test including shorter distance travelled (CD38KO: 2±0.06 vs WT: 3.7±1.1 m, p=0.008), longer time in proximity of the holes (CD38KO: 51.2±11.1 vs WT: 34.6±8.4 s, p=0.027), and shorter distance from the hole (CD38KO: 0.17±0.025 vs WT: 0.23±0.04 m, p=0.038) and less errors (CD38KO: 3.5±2.3 vs WKY: 6±0.7, p=0.04). Brain tissue analysis showed 58% lower superoxide (p

Stroke, Volume 54, Issue Suppl_1, Page AWP50-AWP50, February 1, 2023. Introduction:Stress hyperglycemia is an essential survival response. However, it is associated with poor prognosis after ischemic stroke, and its contribution to collateral failure is not well defined. We investigated whether stress hyperglycemia would be associated with early neurological deterioration (END) in acute large vessel occlusion (LVO) patients who present with mild neurological deficit.Methods:From a multicenter stroke registry, ischemic stroke patients with acute anterior circulation LVO and mild symptoms (NIHSS

Stroke, Volume 54, Issue Suppl_1, Page A104-A104, February 1, 2023. Introduction:Cytochrome b5 reductase 3 (Cyb5R3) is a heme iron reductase that reverses oxidized soluble guanylate cyclase (sGC) heme iron (Fe3+Fe2+) to preserve nitric oxide signaling. Under oxidative stress, such as occurs with sickle cell disease (SCD) and ischemic stroke, Cyb5R3 redox signaling provides resilience against tissue damage. A loss-of-function (roughly 50%) Cyb5R3 missense variant (T117S) occurs with high frequency (0.23 minor allele) in persons of African ancestry, who also suffer a greater burden of sickle cell anemia and ischemic stroke than other races. We hypothesized that Cyb5R3 regulates the erythropoietin response to ischemic stroke in a mouse model of SCD.Methods:Age-matched male SCD mice with wild-type Cyb5R3 (SSWT) or T117S Cyb5R3 (SST117S) underwent middle cerebral artery occlusion (55 min) and reperfusion (48 hr). Blood was sampled at baseline and 48h reperfusion for hematology measurements. Brains were stained with 2,3,5-triphenyltetrazolium chloride to quantify infarct volume. Erythropoietin (EPO), heme oxygenase 1 (HMOX1) and sGC were assayed by Western blot.Results:We found brain infarct volume to be greater in SST117Svs SSWT(63 vs 27 cm3, respectively; P=0.003). Red cells, hematocrit and hemoglobin decreased in SST117Spost-stroke, which was opposite to SSWT(red cells: -13% vs 13%, P=0.01; hematocrit: -20% vs 0%, P=0.03; hemoglobin: -18% vs 3%, P=0.02, respectively). In the absence of stroke (age-matched controls), SSWThad elevated HMOX1 protein compared to SST117S, which normalized in post-stroke SSWTbut was unchanged in post-stroke SST117S. Kidney and plasma EPO levels significantly increased in SSWTpost-stroke, but not in SST117S. In vitro studies using HEK293 cells showed EPO and HMOX1 decrease with Cyb5R3 knockdown by siRNA.Conclusion:Our findings suggest a modifying role for Cyb5R3 in brain-kidney crosstalk during ischemic stroke, wherein loss of T117S Cyb5R3 activity negatively impacts renal and plasma EPO levels and resilience against infarct of ischemic brain tissue. The Cyb5R3 axis on which the brain-kidney-blood response to stroke in SCD turns represents a novel target for precision medicine approaches to managing stroke risk and pathology in SCD carriers of the T117S variant.

Stroke, Volume 54, Issue Suppl_1, Page AWMP31-AWMP31, February 1, 2023. Background:Stroke is a sudden-onset, unexpected life event over which individuals have little control. These features can make the experience of having a stroke extremely stressful, which may potentiate its debilitating effects. We previously identified short-term associations among lifetime stress/trauma exposure (LSE), post-stroke acute stress (AS), Modified Rankin Scale (mRS) and Fugl-Meyer at 90 days post-stroke. However, their association with long-term stroke-related disability remains unknown.Hypothesis:Higher lifetime trauma and AS symptoms will be associated with poorer long-term disability 1-year post stroke.Method:Multi-site national study of patients admitted for a new stroke. Assessments included Acute Stress Disorder Interview 2-10 days post-stroke, LSE 90 days post-stroke, and Stroke Impact Scale (SIS), modified Rankin Scale (mRS), & Telephone Montreal Cognitive Assessment (tMOCA) at 1-year post-stroke. Structural Equation Modeling examined relationships among LSE, AS, and outcomes, controlling for admission NIHSS score and demographics.Results:Among key predictors and covariates (demographics, acute NIHSS), AS immediately post-stroke was the strongest direct correlate of poorer mRS scores and SIS scores at 1-year (ps < .001), and the second strongest direct correlate of tMOCA scores at 1-year; higher d90 LSE was directly associated with poorer SIS (p< .001), and indirectly associated with poorer mRS, SIS, & tMOCA scores at 1-year (allps < .001) through its association with high AS (p< .001) at admission.Conclusion:Lifetime stress and stress symptoms in the acute stroke setting are both associated with disability and cognitive impairment 12 months post-stroke; their assessment may be useful to facilitate early identification of high-risk patients and development of interventions that help improve functional and cognitive outcomes after stroke.

Stroke, Volume 54, Issue Suppl_1, Page ATMP66-ATMP66, February 1, 2023. Introduction:We investigated the relationship between the level of cerebral collateral circulation on arterial spin-labeling (ASL) magnetic resonance imaging (MRI) and cerebrovascular reserve (CVR) on acetazolamide (ACZ)-stress single photon emission computed tomography (SPECT) brain scans in internal carotid artery (ICA) stenosis.Methods:This study enrolled 129 patients with severe ICA stenosis ( >70%). Collateral circulation was assessed in pulsed ASL images based on the presence of arterial transit artifact (ATA) that late-arriving flow appears as serpiginous high ASL signal within cortical vessels. CVR based on rest-SPECT and ACZ-stress SPECT with Tc-99m-ECD was calculated. The ASL CBF maps were independently assessed by two neuroradiologists blinded to clinical information. The two neuroradiologists graded on two slices of ASL images corresponding to Alberta Stroke Program Early Computed Tomography Score (ASPECTS) location using a 4-point scale for ASL intensity.Results:With ACZ-stress SPECT, the 88/129 (68%) patients showed normal CVR and 41/129 (32%) patients showed decreased CVR. In 73/88 (82%) of the normal CVR group patients, ASL showed ATA in ipsilateral to the stenosis. In 19/41 (46%) of the decreased CVR group patients, ASL showed no evidence of ATA in ipsilateral to the stenosis. Significant positive relationship was observed between the normal CVR group and the ATA showing group in ICA stenosis patients (p = 0.001, chi-square test). The ASL-based ASPECTS scores of brain in the ipsilateral side was lower than the scores in the contralateral side to the ICA stenosis (p < 0.0001, Wilcoxon signed rank test). The ASL-based ASPECTS scores of brain ipsilateral side to the ICA stenosis was lower in the reduced CVR group than normal CVR group (p = 0.005).Conclusion:This study demonstrated the statistically significant positive correlation between good collaterals on ASL MRI and intact CVR in patients with ICA stenosis.