Notes

Hydrothermal deterioration associated with proteins.
We have previously reported that human calcified aortic cusps have abundant expression of smooth muscle (SM) markers and co-activators. We hypothesised that cells in bicuspid aortic valve (BAV) cusps and those affected by rheumatic heart valve (RHV) disease may follow a similar phenotypic transition into smooth muscle cells, a process that could be regulated by transforming growth factors (TGFs).

Cusps from eight patients with BAV and seven patients with RHV were analysed for early and late SM markers and regulators of SM gene expression by immunocytochemistry and compared to healthy aortic valves from 12 unused heart valve donors. The ability of TGFs to induce these markers in valve endothelial cells (VECs) on two substrates was assessed.

In total, 7 out of 8 BAVs and all the RHVs showed an increased and atypical expression of early and late SM markers α-SMA, calponin, SM22 and SM-myosin. The SM marker co-activators were aberrantly expressed in six of the BAV and six of the RHV, in a similar regional ps. The similarity between SM marker expression in BAVs and RHVs with our previous study with cusps from patients with aortic stenosis suggests the existance of a common pathological pathway between these different pathologies.
Bicuspid aortic valves and RHVs expressed increased numbers of SM marker-positive VICs and VECs. Concomittantly, these cells expressed MRTF-A and myocardin, key regulators of SM gene expression. TGFβ1 was able to preferentially upregulate SM markers and myocardin in VECs on fibronectin, and fibronectin was found to be upregulated in BAVs and RHVs. These findings suggest a role of VEC as a source of cells that express SM cell markers in BAVs and RHVs. The similarity between SM marker expression in BAVs and RHVs with our previous study with cusps from patients with aortic stenosis suggests the existance of a common pathological pathway between these different pathologies.
Diabetic cardiomyopathy (DCM) is a complex multifaceted disease responsible for elevated heart failure (HF) morbidity and mortality in patients with diabetes mellitus (DM). Patients with DCM exhibit subclinical diastolic dysfunction, progression toward systolic impairment, and abnormal electrophysiology. Hypoglycemia events that occur spontaneously or due to excess insulin administration threaten the lives of patients with DM-with the increased risk of sudden death. However, the molecular underpinnings of this fatal disease remain to be elucidated.

Here, we used the established streptozotocin-induced DCM murine model to investigate how hypoglycemia aggravates DCM progression. We confirmed connexin 43 (Cx43) dissociation from cell-cell interaction and accumulation at mitochondrial inner membrane both in the cardiomyocytes of patients with DM and DCM murine. Here, we observed that cardiac diastolic function, induced by chronic hyperglycemia, was further aggravated upon hypoglycemia challenge. Similar contraumulation of mtCx43 through the MEK/ERK/Src and PI3K/Akt/Src pathways. We provide evidence that Cx43 mislocalization is present in hearts of patients with DM hearts, STZ-induced DCM murine model, and glucose fluctuation challenged NMVMs. Mechanistically, we demonstrated that mtCx43 is responsible for inducing aberrant contraction and disrupts electrophysiology in cardiomyocytes and our results support targeting of mtCx43 in treating DCM.
DCM presents compensatory adaptation of mild mtCx43 accumulation, yet acute hypoglycemia challenges result in further accumulation of mtCx43 through the MEK/ERK/Src and PI3K/Akt/Src pathways. We provide evidence that Cx43 mislocalization is present in hearts of patients with DM hearts, STZ-induced DCM murine model, and glucose fluctuation challenged NMVMs. Mechanistically, we demonstrated that mtCx43 is responsible for inducing aberrant contraction and disrupts electrophysiology in cardiomyocytes and our results support targeting of mtCx43 in treating DCM.
The thioflavin T derivative,
C-Pittsburgh-B (PIB), is used for Alzheimer's disease imaging because it specifically binds to β-amyloid protein deposits in the brain. The aim of this study was to estimate the diagnostic value of combined
C-PIB positron emission tomography/magnetic resonance (PET/MR) in cardiac amyloidosis (CA).

We enrolled 23 heart failure patients with suspected CA based on echocardiographic and electrocardiograph findings. All patients underwent cardiac
C-PIB PET/MR and non-cardiac biopsy within one week. We also enrolled eight healthy volunteers that underwent cardiac
C-PIB PET/MR as a control group. The cardiac magnetic resonance (CMR) protocol included cine imaging, late gadolinium enhancement (LGE), and native and post-contrast T1 mapping. Extracellular volume (ECV) was measured using pre- and post-contrast T1 mapping images. LVEF, IVSD, LVPW, LVmass, LVESV, LVEDV, native T1 value, ECV, and maximum uptake of myocardial tissue-to-blood background ratio (TBR) values were obtaineping values positively correlated with TBRmax values in CA and non-CA patients. In the future, larger cohort studies are necessary to confirm our findings.
11C-PIB PET/MRI is a valuable tool for the accurate and non-invasive diagnosis of CA because it distinguishes CA patients from non-CA patients and healthy subjects with high specificity and sensitivity. Moreover, native T1 mapping values positively correlated with TBRmax values in CA and non-CA patients. In the future, larger cohort studies are necessary to confirm our findings.Coronavirus disease-2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2; CoV2) is a deadly contagious infectious disease. For those who survive COVID-19, post-COVID cardiac damage greatly increases the risk of cardiomyopathy and heart failure. Currently, the number of COVID-related cases are increasing in Latin America, where a major COVID comorbidity is Chagas' heart disease, which is caused by the parasite Trypanosoma cruzi. However, the interplay between indeterminate Chagas disease and COVID-19 is unknown. We investigated the effect of CoV2 infection on heart pathology in T. cruzi infected mice (coinfected with CoV2 during the indeterminate stage of T. cruzi infection). We used transgenic human angiotensin-converting enzyme 2 (huACE2/hACE2) mice infected with CoV2, T. cruzi, or coinfected with both in this study. We found that the viral load in the hearts of coinfected mice is lower compared to the hearts of mice infected with CoV2 alone. We demonstrated that CoV2 infection significantly alters cardiac immune and energy signaling via adiponectin (C-ApN) and AMP-activated protein kinase (AMPK) signaling. Our studies also showed that increased β-adrenergic receptor (b-AR) and peroxisome proliferator-activated receptors (PPARs) play a major role in shifting the energy balance in the hearts of coinfected female mice from glycolysis to mitochondrial β-oxidation. Our findings suggest that cardiac metabolic signaling may differently regulate the pathogenesis of Chagas cardiomyopathy (CCM) in coinfected mice. We conclude that the C-ApN/AMPK and b-AR/PPAR downstream signaling may play major roles in determining the progression, severity, and phenotype of CCM and heart failure in the context of COVID.
The present study aimed to prospectively evaluate the role of metagenomic next-generation sequencing (mNGS) in the etiological diagnosis of patients with perioperative infective endocarditis (IE).

From May 1st, 2019 to December 31st, 2020, a total of 99 patients with IE were enrolled in the present study according to the modified Duke criteria, etiological, and pathological results. 11 non-IE patients undergoing heart valve surgery in the same period were selected as the control group. A blood culture test was performed immediately after admission, and the valves harvested operatively were examined by blood culture and mNGS.

In the IE group, there were 29 cases (29.3%) with positive blood culture, 16 cases (16.2%) with positive valve culture, and 85 cases (85.9%) with positive valve mNGS. SKF-34288 datasheet Compared to culture-based detection, mNGS achieved better performance with a sensitivity, specificity, area under the curve (AUC) of 0.859, 0.727, and 0.793, respectively. The combined approach using culture and mNGS flture method and displayed high accuracy in detecting pathogens in IE patients. This study provided support for the use of mNGS in the etiological diagnosis of IE.
mNGS outperformed the conventional culture method and displayed high accuracy in detecting pathogens in IE patients. This study provided support for the use of mNGS in the etiological diagnosis of IE.
The objective of this study was to evaluate the effectiveness of formal hepatitis C virus (HCV) education on engagement in therapy in persons experiencing homelessness in an on-site shelter-based model of care. As policies to eliminate Medicaid access restrictions to HCV treatment are expanded, patient education is paramount to achieving HCV elimination targets in difficult-to-engage populations including persons experiencing homelessness.

This prospective study was conducted at 4 shelters in San Francisco and Minneapolis from August 2018 to January 2021. Of the 162 HCV Ab-positive participants, 150 participated in a 30-minute HCV education session. Posteducation changes in knowledge, beliefs, barriers to care, and willingness to accept therapy scores were assessed.

Following education, knowledge scores (mean change, 4.4 ± 4.4;
 < .001) and willingness to accept therapy (70% to 86%;
 = .0002) increased. Perceived barriers to HCV care decreased (mean change, -0.8 ± 5.2;
 = .001). Higher baseline knowledge was associated with lesser gain in knowledge following education (coef., -0.7;
 < .001). Posteducation knowledge (odds ratio, 1.2;
 = .008) was associated with willingness to accept therapy.

An HCV educational intervention successfully increased willingness to engage in HCV therapy in persons experiencing homelessness in an on-site shelter-based HCV model of care.
An HCV educational intervention successfully increased willingness to engage in HCV therapy in persons experiencing homelessness in an on-site shelter-based HCV model of care.
To evaluate a modified surgical technique aiming to reduce bleeding and preserve fertility in morbidly adherent placenta by cervical tourniquet in cesarean sections.

The cesarean section operations and the cervical ligation approach were performed by a single expert consultant obstetrician. The general demographics and clinical characteristics for all participants were collected and studied.

Eleven participants were involved. The uterus was preserved in nine patients, whereas two patients had hysterectomy. The mean blood loss was 1688.8ml for patients whose uterus was preserved. The mean length of stay was 5.5days.

Cervical ligation is a simple method that can be applied by junior and experienced obstetricians to preserve the uterus.
Cervical ligation is a simple method that can be applied by junior and experienced obstetricians to preserve the uterus.
Intracerebral hemorrhage (ICH) has limited therapeutic options. We have shown that an intravenous injection of human umbilical cord-derived mesenchymal stromal cells (hUC-MSC) 24 hafter an ICH in rats reduced the residual hematoma volume after a moderate hemorrhage but was inefficient in severe ICH. Here, we investigated whether a treatment in the hyperacute phase would be more effective in severe ICH.

Wistar rats were randomly selected to receive an intravenous injection of hUC-MSC or the vehicle 1 hafter a severe ICH.

The hyperacute treatment with hUC-MSC did not affect the 22-day survival rate, the motor function or the residual hematoma volume.

These results indicate the need for optimization of hUC-MSC-based therapies for severe ICH.
These results indicate the need for optimization of hUC-MSC-based therapies for severe ICH.
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