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

Circulation, Volume 146, Issue Suppl_1, Page A11029-A11029, November 8, 2022. Mitochondrial diseases are some of the most common genetically inherited disorders, yet the prognosis for affected patients has not drastically improved in recent years. Most therapies are supportive as the underlying biochemical derangements in these diseases are incompletely understood. Mitochondrial functions rely on the import of nuclear-encoded proteins, and it has recently been appreciated that defective import of mitochondrial proteins can result in the cytosolic accumulation of these preproteins. The accumulation of these preproteins results in cellular toxicity independently of any changes to the mitochondrial bioenergetic function, raising the possibility that mitochondrial protein import stress may be a yet uncharacterized pathway that links mitochondrial dysfunction with pathology. Here, we model this cytosolic mitochondrial precursor overaccumulation stress (mPOS) in mice through overexpression of the inner mitochondrial membrane protein Adenine Nucleotide Translocase 1 (ANT1). The goal of this study is to determine whether ANT1 can induce mPOS and tissue remodeling prior to the onset of cardiac bioenergetic defects. Using isolated cardiac mitochondria from these mice, we detected a moderate decrease in the levels of Complex I, II ,and IV. By measuring oxygen consumption in these mitochondria from 2-month-old animals, we found only a mild reduction in complex II based state 3 and 4 respirations. No change in complex I-based state 3 and 4 respirations was observed. Using RNAseq and western blot analysis, we find the robust activation of the integrated stress response (ISR). Transcriptomic data further demonstrates a strong upregulation of transcripts involved with 1-carbon metabolism, the amino acid starvation response, and proteolysis. Using echocardiographic evaluation of heart function on anesthetized mice at 6 months old, we find no significant alteration in systolic function. Together these data support the idea that mPOS may be a potent trigger of the ISR in a bioenergetics-independent manner. Whether activation of the ISR can alter cardiac function later in life is being evaluated.

Circulation, Volume 146, Issue Suppl_1, Page A14940-A14940, November 8, 2022. Introduction:Failure of multidrug therapy and the multifactorial nature of kidney injury has paved the path way regenerative medicine with over 45 clinical trials using stem cells-based therapy underway. Neonatal cardiac mesenchymal stem cells (nMSC) are one of the most potent stem cells due to their secretome. HYPOTHESIS: SOD2 and anti-inflammatory miRNAs (miR-214 & 95p) in paracrine secretions (secretome) of nMSC provides renoprotection in a rodent model of glycerol-induced AKI.Methods:nMSC were generated from neonatal myocardium using enzymatic digestion and antibodies-based selection. Secretome was collected by conditioning nMSCs for 72 hours in serum free basal medium. Human kidney cells (HKC) were used forin vitroanti-oxidation assays using cisplatin. THP-1 cells were used for anti-inflammatory assessment. CD1 mice were used for glycerol-induced AKI model. Mice were subjected to AKI via IM glycerol (9mg/kg). nMSC-derived secretome was intravenously administered immediately after, or 4 hours post-glycerol. Blood urea nitrogen (BUN) and creatinine were analyzed in serum. Cell survival/KIM1 was assessed by immunohistology/FACS. Other experiments utilized cisplatin toxicity in HKC.Results:Administration of nMSC secretome (5 or 10mg/kg) at the same time or 4-hours post-glycerol administration significantly reduced serum creatinine and BUN in a glycerol induced AKI animal model. Caspase-9 and KIM1 expression was significantly decreased in tubular cells as compared to placebo at a dose of 10mg/kg. KIM-1 was significantly downregulated as compared to placebo following nMSC-secretome administration. Western blot analysis of HKC treated with cisplatin in presence of nMSC-secretome showed significant reduction in NFkb and pERK expression (p

Circulation, Volume 146, Issue Suppl_1, Page A13918-A13918, November 8, 2022. Introduction:Stress cardiomyopathy (SC) and anterior ST elevation myocardial infarction (AMI) share similar clinical and echocardiographic features on initial presentation, complicating their differentiation. Previously, subtle differences in 12-lead ECG between the two have been reported.Hypothesis:We propose that higher precordial R-wave amplitude on ECG and lower biomarkers values can serve as reliable predictors of SC during initial triage.Methods:Among patients admitted to a single center from 2015-2019 undergoing left heart catheterization (LHC) for suspected AMI, 76 patients with either LHC-proven SC or AMI (38 each) were included. All patients had transthoracic echocardiography (TTE) performed within 24 hours of LHC. Patients were excluded when TTE quality was poor. Left ventricular ejection fraction (LVEF) and speckle-tracking global longitudinal strain (GLS) were calculated from transthoracic apical views. Non-parametric variables were analyzed using Wilcoxon rank sum test. Sensitivity and specificity analyses were performed using ROC curves.Results:LVEF (33+9% vs 33+8%) and GLS (-7.5+2.8% vs -7.9+3.3%) were similar in both groups. R-wave amplitude in ECG leads V1-V2 was higher in SC compared to AMI (V1: 0.96 vs 0.54 mV, p = 0.035; V2: 1.46 vs 0.75 mV, p = 0.037). At index admission, peak pro-BNP was higher (22198 vs 3098, p = 0.002) and peak Troponin-T (1.43 vs 236, p

Circulation, Volume 146, Issue Suppl_1, Page A14174-A14174, November 8, 2022. IntroductionPatients with an abnormal (positive) exercise electrocardiography (ECG), but normal stress echocardiography (+ECG/-Echo) have more adverse cardiac events than patients with a negative ECG and normal stress Echo (-ECG/-Echo). However, it is unclear if ECG/Echo discordance is associated with a greater burden of concurrent subclinical coronary atherosclerosis.MethodsIn the Project Baseline Health Study (PBHS), participants underwent stress Echo and a coronary artery calcium (CAC) scan. For this PBHS substudy, participants with no known coronary artery disease (CAD) were analyzed by stress result: -ECG/-Echo, +ECG/-Echo, or +Echo (with or without +ECG). Patients with a submaximal stress test, uninterpretable ECG, resting wall motion abnormality, and/or baseline ejection fraction

Circulation, Volume 146, Issue Suppl_1, Page A11202-A11202, November 8, 2022. Introduction:Caregivers of patients with heart failure (HF) are at high risk of low quality of life due to stress-related to caregiving. Self-reported measures are commonly used to assess relatively long-term stress related to caregiving. Still, biological markers of stress, a short-term stress measure, are rarely used. There is limited knowledge on whether both can predict the quality of life in caregivers of patients with HF.Hypothesis:The stress biomarker (serum cortisol) and subjective distress related to caregiving (Caregiver Burden Inventory) predict the quality of life in caregivers of patients with HF.Methods:In this cross-sectional study, Taiwanese caregivers of patients with HF completed surveys including stress-related caregiving and quality of life measured by the Caregiving Burden Inventory and the Short Form-36, respectively. A blood sample for serum cortisol was collected between 9 and 12 AM. Independent t-test and multivariable linear regression analysis were conducted adjusting for age, gender, education, marital status, relationship with care-recipient and depressive symptoms (Patient Health Questionnaire).Results:Of the 113 caregivers (mean age 54.5 years, 70.8% female, 78% married/cohabitated), 59% cared for patients with NYHA class III/V. Single caregivers had higher serum cortisol levels than married caregivers (11.4 vs. 8.5, p =.002). Males had a significantly higher serum cortisol level than females (10.7 vs. 8.5, p =.010), but males reported a lower caregiver burden than females (1.3 vs. 1.6, p =.049). Both serum cortisol (β =-.36, P=.012) and caregiver burden (β = -.29, P= .018) were significant predictors of physical well-being. Serum cortisol (β= -.28, p=.026) and caregiver burden (β =-.25, p =.027) also significantly predicted mental well-being.Conclusions:Although stress levels are different by caregivers’ characteristics, both cortisol level and self-report caregiver burden have similar predictability of quality of life in caregivers of patients with HF. Reducing stress and caregiver burden is necessary to improve the quality of life in this population.

Circulation, Volume 146, Issue Suppl_1, Page A14139-A14139, November 8, 2022. Introduction:AHA guidelines recommend non-invasive cardiac testing (NIT) within 72 hours after an emergency department (ED) evaluation for suspected acute coronary syndrome (ACS), after acute myocardial infarction (AMI) has been excluded. However, the effectiveness of this strategy to reduce the risk of future AMI or death, in low-risk patients is contested.Hypothesis:We hypothesized that in patients with low risk based on history, electrocardiogram, age, risk factors and troponin (HEART) based scoring, early NIT may not be beneficial compared to higher risk.Methods:We compared the effectiveness of early NIT vs. no early testing, in a retrospective cohort of adult (age ≥18) members of the Kaiser Permanente Southern California health system from 05/2016-12/2020. We included all adults presenting at EDs with suspected ACS and who had data to compute HEART score. We stratified the cohort into low risk (score 0-3); intermediate risk (score 4-6) and high-risk (score ≥7) based on HEART score. Within each group, confounder adjusted instrumental variables models were used to evaluate the marginal effect of early NIT, and the number needed to treat (NNT) was calculated as the inverse of the absolute composite risk reduction in death/AMI within 30 days of ED discharge.Results:The cohort included 174,936 patients [61% Low risk (mean age 53; female 58%; early NIT 5%), 36% intermediate risk (mean age 71; female 72%; early NIT 18%), and 3% high risk (mean age 74, female 45%; early NIT 23%)]. The risk reduction in 30-day death/AMI due to early NIT increased progressively through the intermediate-risk (NNT = 59) and high-risk groups (NNT = 24) (Table 1). Risk reduction in the low-risk group was not statistically significant.Conclusions:HEART score based high risk patients may benefit the most from early NIT. However, the majority of the suspected ACS cohort was classified as low risk and the benefit of early NIT on 30-day death/AMI was uncertain in this low-risk group.

Circulation, Volume 146, Issue Suppl_1, Page A14263-A14263, November 8, 2022. Introduction:The presence of pulmonary vascular disease (PVD) may be under-recognized during standard hemodynamic evaluation in patients with Fontan physiology. Assessment of pulmonary vascular reserve (VR) (Δ pulmonary artery pressure/Δ cardiac index) utilizing pharmacologic stress testing could be a better way of identifying PVD in pediatric patients. The objective of this study is to diagnose Fontan patients with PVD utilizing pharmacologic stress testing.Hypothesis:Pharmacologic stress testing will unmask Fontan patients as having PVD.Methods:Single center record review of cardiac catheterizations with dobutamine administration in Fontan patients from January 2021 to June 2022. Following acquisition of baseline data on room air, a dobutamine infusion was started at 5 mcg/kg/min with dose escalation as needed until an appropriate heart rate response was achieved. Hemodynamics were reassessed at each dose interval, but data are reported at the highest cardiac index (CI). Abnormal VR was defined as > 3 mmHg/l.Results:Eighteen Fontan patients (87% male) were included. Median age at the time of catheterization was 14 (IQR 11, 16) years with mean duration of Fontan circulation of 9.9 ± 3.9 years. The primary indication for catheterization was exercise intolerance (65%). Dobutamine administration did not result in a significant change in indexed pulmonary vascular resistance (PVRi) (2.1 ± 0.8 v 2.4 ± 1.31 iWU, p = 0.21) or Fontan pressure (12 [IQR 11, 14] v 14 (IQR 12, 15), p=1.0]. Eight patients had a PVRi ≥ 2.0 iWu at baseline; while 4 (22% of the cohort) had a PVRi < 2.0 iWU at baseline but had an abnormal VR.Conclusions:PVD is common in Fontan patients but may be missed in some patients without pharmacologic stress testing. Accurate diagnosis of PVD will allow for optimization of Fontan circulation with pulmonary vasodilators.

Circulation, Volume 146, Issue Suppl_1, Page A14359-A14359, November 8, 2022. Background:Psychosocial stress is associated with worse cardiac outcomes, but little is known about the prognostic impact of marital stress in young adults (≤55 years) with acute myocardial infarction (AMI). We investigated the association between marital stress and 1-year health outcomes in young AMI survivors.Methods:We used data from the VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients), which enrolled people aged 18-55 years with AMI (2008-2012). Marital stress was assessed among married/partnered participants at 1 month post-AMI using the Stockholm Marital Stress Scale, categorized as absent/mild, moderate, and severe. Main outcomes were physical/mental health status, generic/disease-specific quality of life, angina, depressive symptoms, and all-cause readmission at 1 year post-AMI. Linear and logistic regression models were sequentially adjusted for baseline health status, demographics, and socioeconomic factors (including education level, income level, employment status, and insurance status).Results:Among the 1593 married/partnered participants in our study, more women reported severe marital stress than men (39.4% vs 30.4%, p=0.001). Having severe marital stress was associated with worse physical and mental health, lower generic and cardiovascular-specific quality of life, more angina and depressive symptoms, and 1.48 times higher all-cause readmission at 1 year post-AMI. These associations remained significant after adjusting for baseline health score and patient demographics (Table Model 1), but they attenuated and became non-significant when further adjusting for socioeconomic factors (Model 2).Conclusion:Marital stress was associated with worse health outcomes in young AMI patients, which can be partially mediated by socioeconomic factors. Further research is needed to understand this complex relationship and potential causal pathway associated with these findings.

Circulation, Volume 146, Issue Suppl_1, Page A14230-A14230, November 8, 2022. Introduction:Stress echocardiography (SE) is a common functional imaging modality used for the detection of symptomatic coronary artery disease (CAD). Currently, the interpretation of SE relies on sex-based comparators for reporting parameters, including exercise time and functional aerobic capacity. These parameters are based on the cisgender male and female populations but have not been studied among transgender (TG) patients. Thus, we sought to characterize the SE parameters among a group of TG women.Methods:We designed a case-control study of TG women who underwent a SE at the Mayo Clinic. Each TG patient was age-matched with 2 cis-males and 2 cis-females. Demographics, medical history, and SE data were extracted. Conditional logistic regression analysis was performed to compare the TG cohort with each cisgender cohort separately.Results:Among the 43 TG females (age 57.7±9 years, 94.9% white), the prevalence of CAD was less than in cis-males (p=0.013) but similar to cis-females. For SE parameters, TG females had higher resting heart rates than cis-males (median [Q1, Q3]: 80 [71,93] vs 70 [64, 77]; p=0.002). Double product (24816 [21156, 27864] vs 26864 [22444, 30660]; p=0.016), exercise time (7.3 minutes [6,9] vs 8.5 [7.2, 9.5]; p=0.041), and metabolic equivalents (8.2 [7, 10] vs 9.5 [8.2, 10.5]; p=0.018), were all lower in TG females than cis-males. Exercise ejection fraction was higher in the transgender cohort than in cis-females (70 [70, 75] vs 70 [65, 70]; p=0.007). There was no difference in functional aerobic capacity or in the rest or stress wall motion score indices among the groups. Finally, there was no difference in the prevalence of positive electrocardiogram or SE studies.Conclusion:In conclusion, we report for the first time SE profiles for TG females which display an overall distinct phenotype compared to cis-males and cis-females. Larger prospective studies are warranted to further define these parameters for the TG population.

Circulation, Volume 146, Issue Suppl_1, Page A110-A110, November 8, 2022. Background:Vagus nerve stimulation (VNS) has been shown to improve survival and neurological outcomes after cardiac arrest (CA) and resuscitation by improving mitochondrial function, increasing cerebral blood flow, and reducing inflammation. However, the therapeutic cellular and subcellular mechanisms of VNS are not clearly understood in CA injury. Endoplasmic reticulum (ER) stress after cardiac arrest also contributes to cell death and is an underexplored area.Objective:The aim of this study was to investigate the protective effects of customized threshold-adjusted VNS (tVNS) in a rat model of CA and resuscitation in reducing ER stress and cell apoptosis.Methods and Results:Sprague-Dawley rats underwent 12 min asphyxial-CA followed by resuscitation. Rats were assigned to either post-resuscitation tVNS for 2 h or no-tVNS (control). tVNS was applied by electrode placement in the left cervical vagus nerve immediately after resuscitation. The tVNS was determined by a 15-20% reduction from the immediate baseline heart rate as the effective and physiological threshold for each animal. This enabled customized parameters for individual animals. At 2 h post-ROSC, rats were perfused with normal saline, and the whole brain was removed. The whole brain was then processed for protein expression by western blotting. We also prepared sham rats that did not receive CA or tVNS. For measuring ER stress we evaluated the expression of p-IRE1α protein and for apoptosis, we measured p-BAD protein. We observed a significantly higher protein expression of p-IRE1α in whole brain tissue after CA in control groups in comparison to the sham (p

Incontro a Padova sull”ospedale sano’

Objectives
Understanding the pathway by which neighbourhood factors influence glycaemic control may be crucial to addressing health disparities in diabetes. This study aimed to examine if the pathway between neighbourhood factors and glycaemic control is mediated by stress.

Design
Structured equation modelling (SEM) was used to investigate direct and indirect effects in the relationship between neighbourhood factors, stress and glycaemic control, with standardised estimates to allow comparison of paths.

Participants
Data was obtained from 615 adults with type 2 diabetes in the Southeastern United States.

Primary and secondary outcome measures
The primary outcome variable was glycaemic control determined by glycated haemoglobin (HbA1c) within the prior 6 months. Neighbourhood factors included neighbourhood violence, aesthetic quality of the neighbourhood, access to healthy food, and social cohesion. Stress was measured using the perceived stress scale.

Results
In the final model (2(158)=406.97, p

Iniziato studio Humanitas-Cremit. Focus su foto e racconti

Comunicato del 01/10/2022 n°1

Passaggio di consegne con Roberto Speranza