The role of ubiquitin ligases in cardiac disease

Rigorous surveillance of protein quality control is essential for the maintenance of normal cardiac function, while the dysregulation of protein turnover is present in a diverse array of common cardiac diseases. Central to the protein quality control found in all cells is the ubiquitin proteasome system (UPS). The UPS plays a critical role in protein trafficking, cellular signaling, and most prominently, protein degradation. As ubiquitin ligases (E3s) control the specificity of the UPS, their description in the cardiomyocyte has highlighted how ubiquitin ligases are critical to the turnover and function of the sarcomere complex, responsible for the heart’s required continuous contraction. In this review, we provide an overview of the UPS, highlighting a comprehensive overview of the cardiac ubiquitin ligases identified to date. We then focus on recent studies of new cardiac ubiquitin ligases outlining their novel roles in protein turnover, cellular signaling, and the regulation of mitochondrial dynamics and receptor turnover in the pathophysiology of cardiac hypertrophy, cardiac atrophy, myocardial infarction, and heart failure

Does shear wave ultrasound independently predict axillary lymph node metastasis in women with invasive breast cancer?

Shear wave elastography (SWE) shows promise as an adjunct to greyscale ultrasound examination in assessing breast masses. In breast cancer, higher lesion stiffness on SWE has been shown to be associated with features of poor prognosis. The purpose of this study was to assess whether lesion stiffness at SWE is an independent predictor of lymph node involvement. Patients with invasive breast cancer treated by primary surgery, who had undergone SWE examination were eligible. Data were retrospectively analysed from 396 consecutive patients. The mean stiffness values were obtained using the Aixplorer(®) ultrasound machine from SuperSonic Imagine Ltd. Measurements were taken from a region of interest positioned over the stiffest part of the abnormality. The average of the mean stiffness value obtained from each of two orthogonal image planes was used for analysis. Associations between lymph node involvement and mean lesion stiffness, invasive cancer size, histologic grade, tumour type, ER expression, HER-2 status and vascular invasion were assessed using univariate and multivariate logistic regression. At univariate analysis, invasive size, histologic grade, HER-2 status, vascular invasion, tumour type and mean stiffness were significantly associated with nodal involvement. Nodal involvement rates ranged from 7 % for tumours with mean stiffness <50 kPa to 41 % for tumours with a mean stiffness of >150 kPa. At multivariate analysis, invasive size, tumour type, vascular invasion, and mean stiffness maintained independent significance. Mean stiffness at SWE is an independent predictor of lymph node metastasis and thus can confer prognostic information additional to that provided by conventional preoperative tumour assessment and staging

Host specificity of epiphytic diatom (Bacillariophyceae) and desmid (Desmidiales) communities

The nature of the relationships between host plants and associated microalgal epiphyton in freshwater ecosystems is largely undetermined. Many studies assume that the host plant, as a biologically active substrate, must have a direct influence on associated epiphytic communities, whereas other studies favor the view that host plants are a neutral substrate with only indirect effects on epiphytic communities. Here, we addressed the question of whether host plant taxonomic identity influences epiphyton community structure in comparison with other factors (which also provided further insight into the general ecology of freshwater microphytobenthos) by examining four types of natural plant substrates at five freshwater sites in the Czech Republic. The results demonstrated that host plant type significantly affected epiphytic community structure; most notably, the genus Sphagnum was found to support remarkably different epiphytic communities, probably including several microalgal substrate specialists. Other host plants we examined included Utricularia spp., Nymphaea spp., and Potamogeton natans L., all of which were presumably neutral substrates. The differences among the host plants varied among sites, however, suggesting the presence of an interaction between these two factors. Thus, we concluded that host plants may not always provide a neutral substrate for microalgal epiphyton and, consequently, biomonitoring surveys should account for variation relating to this factor. Finally, our work showed that epiphytic diatoms (Bacillariophyceae) and desmids (Desmidiales) adopted similar group strategies, thus allowing for generalizations of patterns across entire microphytobentic communities

A pilot study of community-based occupational therapy for persons with dementia (COTID-IT Program) and their caregivers: evidence for applicability in Italy

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Circulating levels of soluble intercellular adhesion molecule-1 (sICAM-1) independently predict depressive symptom severity after 12 months in heart failure patients

Objective. To determine whether inflammatory markers prospectively predict depressive symptom severity 12 months later in heart failure (HF) patients. Methods. In 30 HF patients we assessed depressive symptom severity by the Beck depression inventory (BDI) at baseline as well as 12 months later. We measured circulating levels of the soluble intercellular adhesion molecule (sICAM)-1, the cytokine interleukin (IL)-6 and the acute phase protein C-reactive protein (CRP) at baseline assessment. Results. sICAM-1 (r=.38, p=.045) but not CRP or IL-6 correlated with BDI scores 12 months later. Hierarchical linear regression analysis revealed that independent of baseline BDI assessment, cardiovascular risk factors, indicators of HF disease severity, and medication intake, sICAM-1 significantly predicted BDI scores 12 months later. sICAM-1 independently explained between 7% (beta=.26, p=.040) and 10% (beta=.35, p=.045) of the total variance in BDI scores 12 months later. Conclusion. The findings from this exploratory analysis suggest that the adhesion molecule sICAM-1 is an independent predictor of depressive symptoms 12 months later in HF patients. Our prospective findings support the suggested role for inflammation in increasing future depressive symptom severity and extend this linkage for the first time to HF

The role of ubiquitin ligases in cardiac disease

Rigorous surveillance of protein quality control is essential for the maintenance of normal cardiac function, while the dysregulation of protein turnover is present in a diverse array of common cardiac diseases. Central to the protein quality control found in all cells is the ubiquitin proteasome system (UPS). The UPS plays a critical role in protein trafficking, cellular signaling, and most prominently, protein degradation. As ubiquitin ligases (E3s) control the specificity of the UPS, their description in the cardiomyocyte has highlighted how ubiquitin ligases are critical to the turnover and function of the sarcomere complex, responsible for the heart’s required continuous contraction. In this review, we provide an overview of the UPS, highlighting a comprehensive overview of the cardiac ubiquitin ligases identified to date. We then focus on recent studies of new cardiac ubiquitin ligases outlining their novel roles in protein turnover, cellular signaling, and the regulation of mitochondrial dynamics and receptor turnover in the pathophysiology of cardiac hypertrophy, cardiac atrophy, myocardial infarction, and heart failure

The Impact of COVID-19 Quarantine on Patients With Dementia and Family Caregivers: A Nation-Wide Survey

Introduction: Previous studies showed that quarantine for pandemic diseases is associated with several psychological and medical effects. The consequences of quarantine for COVID-19 pandemic in patients with dementia are unknown. We investigated the clinical changes in patients with Alzheimer’s disease and other dementias, and evaluated caregivers’ distress during COVID-19 quarantine. Methods: The study involved 87 Italian Dementia Centers. Patients with Alzheimer’s Disease (AD), Dementia with Lewy Bodies (DLB), Frontotemporal Dementia (FTD), and Vascular Dementia (VD) were eligible for the study. Family caregivers of patients with dementia were interviewed by phone in April 2020, 45 days after quarantine declaration. Main outcomes were patients’ changes in cognitive, behavioral, and motor symptoms. Secondary outcomes were effects on caregivers’ psychological features. Results: 4913 patients (2934 females, 1979 males) fulfilled the inclusion criteria. Caregivers reported a worsening in cognitive functions in 55.1% of patients, mainly in subjects with DLB and AD. Aggravation of behavioral symptoms was observed in 51.9% of patients. In logistic regression analysis, previous physical independence was associated with both cognitive and behavioral worsening (odds ratio 1.85 [95% CI 1.42–2.39], 1.84 [95% CI 1.43–2.38], respectively). On the contrary, pandemic awareness was a protective factor for the worsening of cognitive and behavioral symptoms (odds ratio 0.74 [95% CI 0.65–0.85]; and 0.72 [95% CI 0.63–0.82], respectively). Approximately 25.9% of patients showed the onset of new behavioral symptoms. A worsening in motor function was reported by 36.7% of patients. Finally, caregivers reported a high increase in anxiety, depression, and distress. Conclusion: Our study shows that quarantine for COVID-19 is associated with an acute worsening of clinical symptoms in patients with dementia as well as increase of caregivers’ burden. Our findings emphasize the importance to implement new strategies to mitigate the effects of quarantine in patients with dementia