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
Risultati per: Incontinenza urinaria da stress o mista
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Abstract TMP66: Correlation Of Cerebrovascular Reserve Assessed By Acetazolamide-stress Spect With Collaterals On Arterial Spin-labeling MRI In Patients With Carotid Occlusive Disease
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.
Abstract TP237: Cofilin Inhibitor Protects Against Hydrogen Peroxide-induced Neuronal Cytotoxicity Via The Inhibition Of Oxidative Stress And Microglial Cell Activation
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.
Abstract 38: Admission Hyperglycemia In Stroke Patients Increases Oxidative Stress In Red Blood Cells
Stroke, Volume 54, Issue Suppl_1, Page A38-A38, February 1, 2023. Background:Our recent study has shown that admission hyperglycemia in stroke patients is associated with red blood cell (RBC) dysregulation, however, the underlying mechanism is still unclear. In addition to transporting oxygen via hemoglobin, RBCs also carry a robust antioxidant system to remove the reactive oxygen species (ROS) continuously produced from hemoglobin autoxidation (Fig A). It has been reported that in vitro hyperglycemia can increase oxidative stress in RBCs. We thus hypothesize that acute hyperglycemia in stroke patients may also affect the antioxidant system in RBCs.Method:Stroke patients with hyperglycemia and normoglycemia (n=12/group) were prospectively recruited in accordance with IRB protocol. Blood was collected at 2 hr, 24 hr, 72 hr and 3 mon post stroke. RBCs were precipitated from whole blood, and leucocytes were removed with depletion filter. The expression and glycosylation of RBC antioxidants, such as catalase (CAT), superoxide dismutase type 1 (SOD1), glutathione peroxidase 1 (GPX1) and peroxiredoxin 2 (PRX2), were quantified using mass spectrometry-based selected reaction monitoring (SRM) method.Result:CAT, SOD1 and GPX1 showed gradually decreased expression in hyperglycemic stroke patients, which may impair the antioxidant capacity of RBCs (Fig B). The glycosylation level of PRX2 was increased in stroke-related hyperglycemia (Fig C), and increased glycosylation was associated with decreased PRX2 activity (Fig D). Consistent with the expression and glycosylation changes in antioxidants, total RBC antioxidant capacity was reduced in hyperglycemic patients, and ROS was significantly accumulated in RBCs (Fig E).Conclusion:Acute hyperglycemia in stroke patients intensifies RBC oxidative stress by affecting the expression and post-translational modification of RBC antioxidants. Larger studies are underway to verify these findings, and explore how hyperglycemia and RBC oxidative stress influence stroke outcome.
Abstract WMP31: Lifetime Stress, Acute Stress, And Long-term Outcomes After Stroke: A Longitudinal Study
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.
Worsened Stroke Outcome in a Model of Preeclampsia is Associated With Poor Collateral Flow and Oxidative Stress
Stroke, Volume 54, Issue 2, Page 354-363, February 1, 2023. Background:Preeclampsia increases the incidence of maternal stroke, a devastating condition that is on the rise. We investigated stroke outcome in a model of experimental preeclampsia with and without treatment with clinically relevant doses of magnesium sulfate (experimental preeclampsia+MgSO4) compared to normal late-pregnant and nonpregnant rats.Methods:Transient middle cerebral artery occlusion was used to induce focal stroke for either 1.5 or 3 hours. Infarct volume and hemorrhagic transformation were determined as measures of stroke outcome. Changes in core middle cerebral artery and collateral flow were measured by dual laser Doppler. The relationship between middle cerebral artery perfusion deficit and infarction was used as a measure of ischemic tolerance. Oxidative stress and endothelial dysfunction were measured by 3-nitrotyrosine and 8-isoprostane, in brain and serum, respectively.Results:Late-pregnant animals had robust collateral flow and greater ischemic tolerance of brain tissue, whereas experimental preeclampsia had greater infarction that was related to poor collateral flow, endothelial dysfunction, and oxidative stress. Importantly, pregnancy appeared preventative of hemorrhagic transformation as it occurred only in nonpregnant animals. MgSO4did not provide benefit to experimental preeclampsia animals for infarction.Conclusions:Stroke outcome was worse in a model of preeclampsia. As preeclampsia increases the risk of future stroke and cardiovascular disease, it is worth understanding the influence of preeclampsia on the material brain and factors that might potentiate injury both during the index pregnancy and years postpartum.
Comparative efficacy for different age groups of psychological or psychosocial treatments on post-traumatic stress disorder: protocol for systematic review, meta-analysis and meta-regression analysis
Introduction
It remains unknown whether psychological or psychosocial treatments for post-traumatic stress disorder (PTSD) have comparable effects across the life span. This study aims at comparing the effects of psychological/psychosocial treatments for PTSD between different age groups of youth, early-middle adults and late adults.
Methods and analysis
A systematic search will be conducted among thirteen electronic databases, including Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, EMBASE, ERIC, PubMed, SCOPUS, Web of Science, Published International Literature on Traumatic Stress, China National Knowledge Infrastructure Database, the Wanfang database, the Chinese Scientific Journal Database (VIP Database) and ProQuest Dissertations and Theses, from inception to 15 May 2022. Electronic searches will be supplemented by a comprehensive grey literature search in Conference proceedings and trial registries. Randomised controlled trials (RCTs) comparing psychological or psychosocial treatments for PTSD with control conditions in all age groups will be included. The primary outcome is the between-treatments efficacy for PTSD that refers to the outcomes of the RCTs included in the meta-analysis. Effect sizes will be calculated for all comparisons and pooled with a fixed effects model or a random effects model. Differences in the efficacy of psychological/psychosocial therapies for PTSD across the age groups will be examined by stratified analyses and meta-regression analyses.
Ethics and dissemination
Data used in this study will be anonymised. These data will not be used for other purposes than research. Authors who supply the data will be acknowledged. The authors declare that no conflicts of interest exist. The findings of this study will be disseminated through briefing reports, publications and presentations.
Trial registration number
CRD42022334305.
Stress and coping strategies among parents of children with cancer at Tikur Anbessa Specialized Hospital paediatric oncology unit, Ethiopia: a phenomenological study
Objective
This study explores sources of stress, conditions that help reduce stress levels and coping strategies among parents of children with cancer receiving chemotherapy at Tikur Anbessa Specialized Hospital (TASH) in Ethiopia.
Design
A qualitative phenomenological approach was used.
Setting
Parents of children receiving chemotherapy at the TASH paediatric oncology unit.
Participants
Fifteen semistructured in-depth interviews were conducted with nine mothers and six fathers of children with cancer from November 2020 to January 2021.
Results
Sources of stress related to child’s health condition as the severity of the child’s illness, fear of treatment side effects and loss of body parts were identified. Parents mentioned experiencing stress arising from limited access to health facilities, long waiting times, prolonged hospital stays, lack of chemotherapy drugs, and limited or inadequate information about their child’s disease condition and treatment. Other sources of stress were insufficient social support, stigmatisation of cancer and financial problems. Conditions decreasing parents’ stress included positive changes in the child’s health, receiving cancer treatment and access to drugs. Receiving counselling from healthcare providers, getting social support and knowing someone who had a positive treatment outcome also helped reduce stress. Coping strategies used by parents were religious practices including prayer, crying, accepting the child’s condition, denial and communication with health providers.
Conclusion
The main causes of stress identified by parents of children with cancer in Ethiopia were the severity of their child’s illness, expectations of poor treatment outcomes, unavailability of cancer treatment services and lack of social/financial support. Measures that should be considered to reduce parents’ stress include providing psycho-oncological care for parents and improving the counselling available to parents concerning the nature of the child’s illness, its treatment, diagnostic procedures and treatment side effects. It may also be helpful to establish and strengthen family support groups and parent-to-parent communication, improve the availability of chemotherapy drugs and offer more education on coping strategies.
Mindfulness-Based Stress Reduction vs Escitalopram for the Treatment of Anxiety Disorders
This randomized clinical trial evaluates whether mindfulness-based stress reduction is noninferior to escitalopram in the treatment of anxiety disorders.
Feasibility and acceptance of self-hypnosis to reduce chronic stress levels on family in-home caregivers of elderly people: protocol for the POSSAID pilot, randomised, wait-list controlled trial
Introduction
Family members who care for elderly people experience high levels of chronic stress because of the intensive assistance they provide permanently to those who are losing their autonomy. Often considered a burden, this stress causes serious consequences to their health and worsens their quality of life (QoL). Reducing caregivers’ chronic stress via self-hypnosis protocols may be an effective treatment. The objective is to evaluate the feasibility and acceptance of self-hypnosis protocols taught by hypnotherapy-trained nurses to reduce the chronic stress of in-family caregivers.
Methods and analysis
This study is a prospective, monocentric, non-blinded, parallel, pilot, randomised waitlist-controlled trial that will be conducted at the University Hospital of Reunion Island. Sixty participants will be randomly allocated to one of two groups: a self-hypnosis group (intervention) or a waitlist control group. After an 8-week training programme, intervention participants will practice self-hypnosis for ten minutes/day over 8 weeks and subsequently be followed up for 16 weeks thereafter. The primary outcome is to assess the feasibility of a 16-week self-hypnosis protocol for in-family caregivers. Secondary outcomes include the evaluation of the effects of practising self-hypnosis among in-family caregivers of elderly people concerning their stress levels, sleep disorders, levels of fatigue, and QoL at 2, 4 and 8 months on an exploratory basis.
Ethics and dissemination
Ethics approval was obtained from the Institutional Ethics Committee CPP Ile de France VI—Groupe Hospitalier Pitié Salpêtrière on 14 April 2021 (ID RCB: 2021-A00009-32). All participants will receive information about the trial in verbal and written forms. They will give an oral consent which is notified in a dedicated research file prior before enrolment. Results will be published in peer-reviewed journals as well as presented and disseminated at conferences.
Trial registration number
NCT04909970.
Ema, rischio stress sistemi sanitari da Covid e influenza
Per circolazione concomitante, assieme a virus sinciziale
Describing post-traumatic stress disorder and its associations with depression, anxiety and insomnia: a descriptive study in Italian adults with Marfan syndrome during the COVID-19 third wave
Objective
The evaluation of post-traumatic stress disorder (PTSD), depression, anxiety and insomnia in patients with Marfan syndrome (MFS) during the third wave of the COVID-19 pandemic in a region of northern Italy (Lombardy) and the investigation of which mental health, sociodemographic and clinical factors were associated with PTSD.
Design
Descriptive observational design with cross-sectional data collection procedure.
Setting
A single Italian MFS-specific specialised and reference centre in Lombardy (Italy) between February and April 2021.
Participants
112 adults with MFS. The majority of participants were female (n=64; 57.1%), with a high school diploma (n=52; 46.4%) and active workers (n=66; 58.9%). The mean age was 41.89 years (SD=14.00), and the mean time from diagnosis was 15.18 years (SD=11.91).
Primary and secondary outcomes
Descriptive statistics described PTSD, which was the primary outcome, as well as depression, anxiety and insomnia, which were the secondary outcomes. Four linear regression models described the predictors of PTSD total score and its three domains: avoidance, intrusion and hyperarousal.
Results
One out of 10 patients with MFS had mild psychological symptoms regarding depression, anxiety and insomnia, and scores of PTSD that indicated clinical worries about the mental health status. The presence of PTSD was mainly predicted by anxiety (β=0.647; p
Qualitative study to explore UK medical students and junior doctors experiences of occupational stress and mental health during the COVID-19 pandemic
Objectives
This qualitative study aimed to explore the occupational experiences of medical students and junior doctors working during the COVID-19 pandemic. In particular, the research sought to identify factors which mediated work stress, barriers to disclosing mental health problems and levels of support medical students and junior doctors received during the pandemic.
Design
This study was a form of thematic analysis and adopted an inductive, ‘bottom-up’ approach, in which coded categories were derived from rich, descriptive data.
Setting
Semistructured interviews were conducted online with UK-based medical students and junior doctors. Interviews were recorded, and analysis was done by coding salient quotes into themes.
Participants
The final sample consisted of seven junior doctors and eight medical students, during the summer of 2021.
Results
High levels of occupational stress were identified, which were exacerbated by COVID-19. A number of organisational difficulties associated with the pandemic compounded participants’ experiences of work stress. Participants recognised progress towards promoting and managing mental health within the profession but may still be reluctant to access support services. Barriers to disclosure included fear of stigmatisation, concerns about adding to colleagues’ workloads, lack of clarity about career implications and mistrust of occupational health services.
Conclusions
While attitudes towards mental health have improved, medical students and junior doctors may avoid seeking help. Given the immense pressures faced by health services, it is imperative that extra measures are implemented to minimise work-stress, encourage help-seeking behaviours and promote supportive work cultures.
Iss, scoperto un marcatore di malattie collegate allo stress
Soprattutto in donne con un’infanzia con esperienze avverse
Antepartum and labour-related single predictors of non-participation, dropout and lost to follow up in a randomised controlled trial comparing internet-based cognitive-behaviour therapy with treatment as usual for women with negative birth experiences and/or post-traumatic stress following childbirth
Objectives
Internet-based interventions are often hampered by high dropout rates. The number of individuals who decline to participate or dropout are reported, but reasons for dropout are not. Identification of barriers to participation and predictors of dropout may help improve the efficacy of internet-based clinical trials. The aim was to investigate a large number of possible predictors for non-participation and dropout in a randomised controlled trial for women with a negative birth experience and/or post-traumatic stress following childbirth.
Setting
A childbirth clinic at a university hospital in Sweden.
Participants
The sample included 1523 women who gave birth between September 2013 and February 2018. All women who rated an overall negative birth experience on a Likert scale, and/or had an immediate caesarean section (CS), and/or severe postpartum haemorrhage (≥ 2000 mL) were eligible.
Methods
Demographic, antepartum, and labour-related/postpartum predictors were investigated for non-participation (eligible but denied participation), pre-treatment dropout (prior to intervention start), treatment dropout, and loss to follow-up. Descriptive statistics and logistic regression were used in the data analysis.
Results
A majority (80.3 %) were non-participants. Non-participation was predicted by lower level of education, being foreign-born, no experience of counselling for fear of childbirth, multiparity, vaginal delivery (vs CS and vacuum-assisted delivery) and absence of: preeclampsia, anal sphincter injury and intrapartum fetal distress. Pretreatment dropout was predicted by the absence of severe haemorrhage. Treatment dropout was predicted by vaginal delivery (vs immediate CS), vertex presentation and good overall birth experience. Loss to follow-up was predicted by vaginal delivery (vs immediate CS or vacuum-assisted delivery) and absence of intrapartum fetal distress.
Conclusions
Mothers with no obstetric complications were more likely to not participate and dropout at different time points. Both demographic, antepartum and obstetrical variables are important to attend to while designing procedures to maximise participation in internet-delivered cognitive–behavioral therapy.
Trial registration number
ISRCTN39318241
Stress Testing in High-Risk Patients after PCI
New England Journal of Medicine, Volume 387, Issue 21, November 2022.