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

Objectives
Non-alcoholic fatty liver disease (NAFLD) can persist in the stage of simple hepatic steatosis or progress to steatohepatitis (NASH) with an increased risk for cirrhosis and cancer. We examined the mechanisms controlling the progression to severe NASH in order to develop future treatment strategies for this disease.

Design
NFATc1 activation and regulation was examined in livers from patients with NAFLD, cultured and primary hepatocytes and in transgenic mice with differential hepatocyte-specific expression of the transcription factor (Alb-cre, NFATc1c.a . and NFATc1/ ). Animals were fed with high-fat western diet (WD) alone or in combination with tauroursodeoxycholic acid (TUDCA), a candidate drug for NAFLD treatment. NFATc1-dependent ER stress-responses, NLRP3 inflammasome activation and disease progression were assessed both in vitro and in vivo.

Results
NFATc1 expression was weak in healthy livers but strongly induced in advanced NAFLD stages, where it correlates with liver enzyme values as well as hepatic inflammation and fibrosis. Moreover, high-fat WD increased NFATc1 expression, nuclear localisation and activation to promote NAFLD progression, whereas hepatocyte-specific depletion of the transcription factor can prevent mice from disease acceleration. Mechanistically, NFATc1 drives liver cell damage and inflammation through ER stress sensing and activation of the PERK-CHOP unfolded protein response (UPR). Finally, NFATc1-induced disease progression towards NASH can be blocked by TUDCA administration.

Conclusion
NFATc1 stimulates NAFLD progression through chronic ER stress sensing and subsequent activation of terminal UPR signalling in hepatocytes. Interfering with ER stress-responses, for example, by TUDCA, protects fatty livers from progression towards manifest NASH.

Circulation, Volume 146, Issue 19, Page 1483-1485, November 8, 2022.

Introduction
The diagnosis, progression or recurrence of cancer is often highly traumatic for family caregivers (FCs), but systematic assessments of distress and approaches for its prevention and treatment are lacking. Acute leukaemia (AL) is a life-threatening cancer of the blood, which most often presents acutely, requires intensive treatment and is associated with severe physical symptoms. Consequently, traumatic stress may be common in the FCs of patients with AL. We aim to determine the prevalence, severity, longitudinal course and predictors of traumatic stress symptoms in FCs of patients with AL in the first year after diagnosis, and to understand their lived experience of traumatic stress and perceived support needs.

Methods and analysis
This two-site longitudinal, observational, mixed methods study will recruit 223 adult FCs of paediatric or adult patients newly diagnosed with AL from two tertiary care centres. Quantitative data will be collected from self-report questionnaires at enrolment, and 1, 3, 6, 9 and 12 months after admission to hospital for initial treatment. Quantitative data will be analysed using descriptive and machine learning approaches and a multilevel modelling (MLM) approach will be used to confirm machine learning findings. Semi-structured qualitative interviews will be conducted at 3, 6 and 12 months and analysed using a grounded theory approach.

Ethics and dissemination
This study is funded by the Canadian Institutes of Health Research (CIHR number PJT 173255) and has received ethical approval from the Ontario Cancer Research Ethics Board (CTO Project ID: 2104). The data generated have the potential to inform the development of targeted psychosocial interventions for traumatic stress, which is a public health priority for high-risk populations such as FCs of patients with haematological malignancies. An integrated and end-of-study knowledge translation strategy that involves FCs and other stakeholders will be used to interpret and disseminate study results.

Objective
Mindfulness-based stress reduction (MBSR) is a meditation-based therapy originally recommended for stress management. However, it is currently used to alleviate sleep disturbances. Therefore, this contemporary systematic review aimed to elucidate the clinical effects of MBSR on sleep quality and sleep-related daytime impairment in adults with sleep disturbances, including chronic insomnia disorders.

Design
Systematic review and meta-analysis of randomised controlled trials (RCTs).

Methods
A comprehensive search was conducted using the following databases: Ovid MEDLINE, AMED, Ovidembase, PsycINFO, Cochrane Library, CINAHL, and four domestic databases: KoreaMed, KISS, KMbase and NDSL. The final search update was performed in June 2022. Two researchers independently selected relevant studies, assessed the risk of bias and extracted the data.

Results
Of the 7516 records searched, 20 RCTs and 21 reports were included. In the subgroup analysis, MBSR did not improve objective or subjective sleep quality in chronic insomnia and cancers. However, MBSR versus waitlist control might have been effective in improving subjective sleep quality, but with substantial heterogeneity (standardised mean difference=–0.32; 95% CI: –0.56 to –0.08; I2=71%). In addition, MBSR compared with active control did not improve the sleep-related daytime impairments including depression, anxiety, stress, fatigue and quality of life. The overall risk of bias included in this review was a concern because of performance and detection bias.

Conclusions
MBSR might be ineffective for improving sleep quality in patients with chronic insomnia and cancers. In addition, more than half of the RCTs included in this review had small sample sizes and were vulnerable to performance and detection biases. Therefore, well-designed RCTs with larger sample sizes are required to confirm the clinical effects of MBSR in adults with sleep disturbances.

PROSPERO registration number
CRD42015027963.

Comunicato del 29/10/2022 n°3

Circulation, Volume 146, Issue Suppl_1, Page A12932-A12932, November 8, 2022. Introduction:Exercise Stress Echocardiography (ESE) is recommended as a screening tool for the evaluation of Coronary Artery Disease (CAD) in patients with suspected Radiation-Induced Heart Disease (RIHD). Up to now, studies have only evaluated its association with the extent of CAD.HypothesisCancer survivors treated with chest Radiotherapy (RT) that undergo an ESE and have a +ESE develop more MACE than those who have -ESE.Methods:A retrospective, descriptive, cohort study was conducted. Patients who had chest RT and underwent ESE with Treadmill Bruce Stress Protocol, from 2000 to 2012, at Mayo Clinic Rochester and Mayo Clinic Health System were included. A univariate analysis was performed to characterize the population. An analysis including Kruskal Wallis and Pearson Chi-Squared tests was completed to identify variables associated with + SE (Table 1). Multivariable Cox Model for MACE was conducted and is shown in Table 2. A time-to-event curve using Kaplan-Meier estimates is shown in Figure 1.Results:We identified 113 patients, with a mean age of 67 years and a median follow-up of 15.1 years. Of those, 99% were female, 98% were breast cancer survivors, 59% had HTN, 14% DM, 11% AFib, 2% COPD, and 12% had a history of MI. All the patients received >3000cGy of Photon RT, and 57% were treated with systemic cancer therapies. A +ESE was seen in 20.3% of the patients with no significant difference in METS achieved compared with patients who had a -ESE. COPD, RT dose, and systemic therapies, specifically doxorubicin, were associated with a +ESE. The cumulative incidence of MACE was higher in the group of +ESE (p=0.029). After adjustment for HTN, DM, smoking history, hyperlipidemia, and prior MI, the HR for MACE associated with a +ESE was 1.97 (1.09-3.59).Conclusion:MACE was more frequent in patients with a +ESE who received chest RT and doxorubicin versus -ESE. These results support the usefulness of ESE in cancer survivors after RT as a cardiovascular screening tool.

Circulation, Volume 146, Issue Suppl_1, Page A9376-A9376, November 8, 2022. Introduction:Our previous study has shown that 6-week low-Mg diet-induced hypomagnesemia results in mitochondrial dysfunction, cardiac diastolic dysfunction, and seizure-related death. Transient receptor potential cation channel subfamily M 7 (TRPM7) is a Mg transporter with both channel and kinase function located in the plasma membrane. We investigated the role of TRPM7 in hypomagnesemia-associated changes.Methods:For cardiac-specific knockdown of TRPM7, pAAV[miR30]-cTnT >EGFP:Scramble-shRNA as control (Con) and pAAV[miR30]-cTnT >EGFP:TRPM7 shRNA as TRPM7 knockdown (T7KD) were injected into mice through the jugular vein at 10 weeks old. One week later, mice were fed with a normal diet (nlMg, 2000 mg/kg Mg) or a low-Mg diet (HypoMg, 15-30 mg/kg Mg) for 4 weeks.Results:TRPM7 was increased significantly in wild type mouse hearts under the low-Mg diet (1.45±0.18-fold of mice with normal diet, P

Circulation, Volume 146, Issue Suppl_1, Page A15056-A15056, November 8, 2022. Ischemic heart disease (IHD), a major cause of heart failure, is characterized by metabolic dysfunction and myocardial cell death. Cellular hypoxia activates hypoxia inducible factor 1α (HIF1α) to initiate metabolic, angiogenic, and growth-factor related responses. Under normoxia, HIF1α is degraded by prolyl hydroxylase (PHD) domain-containing proteins via the proteasome. Due to the short half-life of HIF1α (

Circulation, Volume 146, Issue Suppl_1, Page A12063-A12063, November 8, 2022. Introduction:Antidepressants, namely selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are efficacious in reducing posttraumatic stress disorder (PTSD) symptoms, but their implications for cardiovascular health are unclear. Although SSRI/SNRI treatment could improve PTSD—thus decreasing cardiovascular risk, antidepressant use has also predicted cardiovascular events. This study examined if antidepressant use was associated with developing ischemic heart disease (IHD) in women veterans with PTSD.Methods:The Veterans Affairs (VA) electronic health record (EHR) database was used to identify women veterans with PTSD who engaged with VA healthcare from 2000-2019. Antidepressant use (documented in the EHR) was categorized as SSRIs, SNRIs, both SSRIs/SNRIs, other, or none (ref). We used Cox regression with time-varying exposure and covariates to estimate effects of antidepressants on risk of incident IHD (angina, MI, CAD). Once a woman was exposed to antidepressants, she was considered exposed until IHD onset or censoring. Age, race, ethnicity, and a range of time-varying risk factors [traditional risk factors (e.g., hypertension), other medical risk factors (e.g., obesity), women-specific risk factors (e.g., preeclampsia), psychiatric risk factors (e.g., depression)], were covariates.Results:The analytic sample comprised 143,324 women without IHD at start of follow-up; mean age was 36.1 years (SD=11.0). Over a median follow-up of 8.6 years, there were 6,633 incident IHD cases. When adjusting for demographics and traditional IHD risk factors, exposure to SNRIs was associated with a 33% greater rate of IHD (95% CI: 1.24-1.43), SSRIs with a 27% greater rate (95% CI: 1.20-1.34), both SSRIs/SNRIs with a 59% greater rate (95% CI: 1.01-2.49), and other antidepressants with a 24% greater rate (95% CI: 1.17-1.31). Associations with SNRIs (HR=1.21, 95% CI: 1.12-1.30), SSRIs (HR=1.15, 95% CI: 1.09-1.22), and other antidepressants (HR=1.19, 95% CI: 1.13-1.26) remained significant in fully adjusted models.Conclusions:Antidepressant use in women veterans with PTSD may exacerbate risk of IHD. Mechanism-focused research and further work in women veterans without PTSD is also needed.

Circulation, Volume 146, Issue Suppl_1, Page A12929-A12929, November 8, 2022. Introduction:Posttraumatic stress disorder (PTSD) has been associated with ischemic heart disease in women veterans. To date, the evidence for the potential association of PTSD with other cardiovascular disorders remains limited. Furthermore, the overwhelming majority of the research in this area has been conducted predominately in men. The goal of this investigation was to evaluate the association of PTSD with incident stroke in a large cohort of women veterans.Methods:Veterans Affairs (VA) electronic health records were used to identify women veterans aged ≥18 years who visited any VAs nationwide from 1/1/2000-12/31/2017. Diagnosis of each risk factor and disorder was based on administrative billing codes (International Classification of Disease versions 9 and 10). The final study cohorts included 1:2 matched group of patients with and without PTSD respectively. The cohorts were matched for age, traditional risk factors such as diabetes, hypertension, hyperlipidemia and smoking, as well as obesity, chronic kidney disease, psychiatric disorders (depression, anxiety), female specific risk factors (e.g., pre-eclampsia), drug and alcohol dependence, neuroendocrine disorders (e.g., hypo or hyperthyroidism), and number of visits. Cox regression was used to model incident stroke as a function of PTSD.Results:The study population included 398,769 patients, including 132,293 with PTSD and 265,846 matched patients without PTSD. The cox regression analysis revealed that PTSD was significantly associated with greater rates of incident stroke (hazard ratio [HR]=1.64, 95% confidence interval: 1.43-1.86, p

Circulation, Volume 146, Issue Suppl_1, Page A14496-A14496, November 8, 2022. Introduction:Diet induced obese (DIO) mice display increased inducible atrial fibrillation (AF) and an overall increase in reactive oxygen species (ROS) production. NADPH oxidase 2 (NOX2), a major source of cytosolic ROS production in human atria, has been implicated in AF independent of obesity and is significantly increased in the atria of DIO mice. Although treatment with MitoTEMPO, a mitochondrial specific antioxidant reduced AF burden in DIO mice, the actual role of NOX2 in increasing ROS production and atrial remodeling in the context of obesity-induced AF remains unclear.Hypothesis:To test the hypothesis that increased NOX2 modulates atrial remodeling in obesity-induced AF, we used control mice, DIO andNox2-KO mice fed with a 60% HFD for 10 weeks (DIO-KO) and DIO mice treated with a NOX2 blocker, apocynin (DIO-Apocynin).Methods:Trans-esophageal rapid (TE) pacing was used to look at the AF phenotype. Cellular electrophysiology (EP), Western blotting, whole-cell patch clamping were performed to study ion channel remodeling and ROS production.Results:All three DIO mouse groups displayed significantly greater body weight compared to their respective controls (Figure A) After TE pacing, DIO-Apocynin mice displayed 28.26 ± 25.40 s and DIO-KO mice displayed 17.43 ± 31.80 s compared to 167.3 ± 168.9 s in DIO mice (Figure B). NOX2 inhibition reversed obesity-induced ion channel remodeling of potassium channels such asKCNQ1andKCNE1encoding for the IKs current andKCNA5encoding for the IKur current and also reduced mediators of oxidative stress. (Figure C-M) Lastly, voltage clamp in DIO-KO mice showed that NOX2 inhibition reverses obesity-induced IK current increase. (Figure N-O)Conclusions:Thus, these results prove that antioxidant therapy targeting Nox2 abrogated ion channel remodeling and reversed the obesity-induced AF burden. Our findings show the importance of targeting specific antioxidant pathways to manage the AF in patients with obesity.

Circulation, Volume 146, Issue Suppl_1, Page A15067-A15067, November 8, 2022. Introduction:Ischemia with non-obstructive coronary arteries (INOCA) is a relatively new condition, often observed in patients with angina. However, the exact pathophysiology of INOCA is not fully understood, and its management remains very debated.Hypothesis:We hypothesized that admission hyperglycemia in INOCA patients could be associated with the risk of being re-hospitalized for chest pain.Methods:We evaluated INOCA patients referred to our Institution between 2016 and 2021 for percutaneous coronary intervention (PCI). We divided our population in quintiles according to the values of the stress hyperglycemia ratio (SHR), calculated as the ratio of admission blood glucose (expressed as mmol/L) and HB1Ac (%). We calculated Kaplan-Meier product limits for cumulative ratio of reaching the endpoint and we applied the log-rank test. To further confirm our results, we performed a multivariable analysis in order to adjust for potential confounders.Results:2874 INOCA patients were enrolled in our study. At 1-year follow-up, the risk of hospitalization for chest pain was progressively higher in patients with higher SHR values (p

Circulation, Volume 146, Issue Suppl_1, Page A14497-A14497, November 8, 2022. Introduction:Hypertensive response during stress echocardiography has been predominately studied in a healthy population without many comorbidities, unlike the patients for which these tests are indicated. We performed a retrospective study identifying clinical predictors of hypertensive response to both exercise (EXE) and dobutamine (DSE) stress echo.Methods:Retrospective analysis was performed on all patients who underwent stress echo from January 1, 2015 to February 28, 2017 in a tertiary care academic center. Patient demographics, comorbidities, medications and stress echo parameters were evaluated. Patients were characterized based on stress echo completed as EXE or DSE. The primary outcome was hypertensive response.Results:4670 patients were enrolled: 1238 in the DSE group and 3432 in the EXE group. On multivariable analysis, only resting SBP remained a significant predictor of hypertensive response during DSE (odds ratio (OR) per 20mmHg 3.21, CI 1.57-6.59,p=.001) with an AUC of 0.76. On multivariable analysis, obesity (OR 2.27, CI 1.08-4.8,p=.03), diabetes (OR 3.24, CI 1.22-8.6,p=.02), resting SBP (OR 4.44, CI 2.35-8.38,p

Circulation, Volume 146, Issue Suppl_1, Page A14778-A14778, November 8, 2022. Introduction and Hypothesis:Arterial healing following stent implantation involves a series of biological reactions such as thrombosis, inflammation, neointimal regeneration. Clinical evidences have shown favorable arterial healing after thin-strut stents, however, there has been a lack ofin vivoimaging evidence on how strut thickness affect vascular healing process. We evaluated local endothelial shear stress (ESS) and healing response of a thin-strut bioresorbable scaffold (BRS, 100μm) compared to first-generation 157μm-thickness ABSORB.Methods and Results:BRS and ABSORB were simultaneously implanted in left coronary arteries of the same pigs (n=7). Detailed scaffolded-artery 3D model was reconstructed based on OCT and angiography. Scaffold-related inflammation response was serially assessed by dual-modal OCT-near-infrared fluorescence (OCT-NIRF) molecular imaging using macrophage-mannose receptor-Cy7 as an inflammation-targeting agent. On ESS analysis, regions with athero-prone low ESS were significantly greater in thick-ABSORB compared to BRS. Dual-modal OCT-NIRF imaging visualized arterial inflammation activity at peri-strut regionsin vivo(Figure). Based on coregistered ESS-NIRF data, we found a significant inverse correlation was found between ESS and NIRF activity (p

Circulation, Volume 146, Issue Suppl_1, Page A10351-A10351, November 8, 2022. Introduction:The cumulative burden of chronic stress and life events can be measured by Allostatic load (AL), whose high values are related to poorer health outcomes and increased risk of cardiovascular disease (CVD). The primary objective of this study is to analyze the impact of androgen deprivation therapy (ADT) on AL variation in patients upon diagnosis of prostate cancer (PC).Hypothesis:ADT may increase AL variation in prostate cancer patients.Methods:Data were obtained from a Cleveland area integrated health care systems informatics platform. The initial cohort included males ≥18 years diagnosed with PC between 2005 and 2022. AL was calculated using multiple markers representing the cardiovascular, metabolic, and immune systems (Table 1) before diagnosis and monthly during the first year. ADT use was captured based on prescribed medications. A linear-mixed-effects model, adjusted for patient demographics, CVD risk factors, and cancer characteristics, and treatment, was used to study AL monthly variation. The analysis was stratified by Non-Hispanic White (NHW) and Non-Hispanic Black (NHB) race.Results:We analyzed a total of 7,168 PC adenocarcinoma patients (31.7% NHB vs 68.3% NHW), of which 20.9% received ADT. NHBs had higher AL pre-PC diagnosis than NHWs (p=0.001). AL monthly variation was 0.15 (±0.02) higher in all PC patients on ADT (p

Circulation, Volume 146, Issue Suppl_1, Page A15731-A15731, November 8, 2022. Reactive oxygen species (ROS) exacerbate atherosclerosis (athero). ROS levels are elevated by specific non-coding, small nucleolar (sno) RNAs encoded within introns of theRpl13agene. We therefore tested the hypothesis that these snoRNAs promote athero, using “snoKO” mice deficient inRpl13asnoRNAs, but not inRpl13aitself. ROS levels assessed by CellROX Orange were 35% lower in snoKO than snoRNA+/+aorta frozen sections (p