61 research outputs found
Nuove tecniche di prospezione archeologica mediante strumenti multifrequenza
EnIn this work we present some results obtained in a measurement survey performed with a stepped frequency Ground Penetrating Radar (GPR). The GPR and the survey at hand have been conceived for archaeological purposes.The stepped frequency GPR has been developed by the Italian Research Consortium CO.RI.S.T.A. in the framework of the ARCHEO project, founded by Italian M.U.R.S.T. The system can work within a large bandwidth and both in ungated and gated mode. It is equipped with a positioning system able to move the transmitting and receiving antennas of the GPR independently on each other and to place them automatically and in a precise fashion. The GPR has been tested first in laboratory of CO.RI.S.T.A., then in a controlled site, and finally in the real archaeological site of Cales, near Capua (Southern Italy), preventively and appositely studied by a team of archaeologists. The final results obtained in the field have been coherent with a previous prospecting performed at Cales and have individuated some new further buried targets, whose nature is still unknown at the moment
Cardiac Hypertrophy: from Pathophysiological Mechanisms to Heart Failure Development
Cardiac hypertrophy develops in response to increased workload to reduce ventricular wall stress and maintain function and efficiency.
Pathological hypertrophy can be adaptive at the beginning. However, if the stimulus persists, it may progress to ventricular chamber dilatation,
contractile dysfunction, and heart failure, resulting in poorer outcome and increased social burden. The main pathophysiological
mechanisms of pathological hypertrophy are cell death, fibrosis, mitochondrial dysfunction, dysregulation of Ca2+-handling proteins,
metabolic changes, fetal gene expression reactivation, impaired protein and mitochondrial quality control, altered sarcomere structure,
and inadequate angiogenesis. Diabetic cardiomyopathy is a condition in which cardiac pathological hypertrophy mainly develop due to
insulin resistance and subsequent hyperglycaemia, associated with altered fatty acid metabolism, altered calcium homeostasis and inflammation.
In this review, we summarize the underlying molecular mechanisms of pathological hypertrophy development and progression,
which can be applied in the development of future novel therapeutic strategies in both reversal and prevention
Pathophysiological mechanisms and clinical evidence of relationship between Nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease
Evidence suggests a close connection between Nonalcoholic Fatty Liver Disease (NAFLD) and increased cardiovascular (CV) risk. Several cross-sectional studies report that NAFLD is related to preclinical atherosclerotic damage, and to coronary, cerebral and peripheral vascular events. Similar results have been showed by prospective studies and also by meta-analyzes on observational studies. The pathophysiological mechanisms of NAFLD are related to insulin resistance, which causes a dysfunction in adipokine production, especially adiponectin, from adipose tissue. A proinflammatory state and an increase in oxidative stress, due to increased reacting oxygen species (ROS) formation with consequent oxidation of free fatty acids and increased de novo lipogenesis with accumulation of triglycerides, are observed. These mechanisms may have an impact on atherosclerotic plaque formation and progression, and they can lead to increased cardiovascular risk in subjects with NAFLD. This review extensively discusses and comments current and developing NAFLD therapies and their possible impact on cardiovascular outcome
Non-Alcoholic Fatty Liver Disease: From Pathogenesis to Clinical Impact
Non-Alcoholic Fatty Liver Disease (NAFLD) is caused by the accumulation of fat in over 5%
of hepatocytes in the absence of alcohol consumption. NAFLD is considered the hepatic manifestation
of metabolic syndrome (MS). Recently, an expert consensus suggested as more appropriate the term
MAFLD (metabolic-associated fatty liver disease). Insulin resistance (IR) plays a key role in the
development of NAFLD, as it causes an increase in hepatic lipogenesis and an inhibition of adipose
tissue lipolysis. Beyond the imbalance of adipokine levels, the increase in the mass of visceral
adipose tissue also determines an increase in free fatty acid (FFA) levels. In turn, an excess of
FFA is able to determine IR through the inhibition of the post-receptor insulin signal. Adipocytes
secrete chemokines, which are able to enroll macrophages inside the adipose tissue, responsible, in
turn, for the increased levels of TNF-. The latter, as well as resistin and other pro-inflammatory
cytokines such as IL-6, enhances insulin resistance and correlates with endothelial dysfunction and
an increased cardiovascular (CV) risk. In this review, the role of diet, intestinal microbiota, genetic
and epigenetic factors, low-degree chronic systemic inflammation, mitochondrial dysfunction, and
endoplasmic reticulum stress on NAFLD have been addressed. Finally, the clinical impact of NAFLD
on cardiovascular and renal outcomes, and its direct link with type 2 diabetes have been discussed
Bipolar Patients and Bullous Pemphigoid after Risperidone Long-Acting Injectable: A Case Report and a Review of the Literature
Neuropsychiatric disorders are found to be associated with bullous pemphigoid (BP), an autoimmune subepidermal blistering disease. Antipsychotics have emerged as possible inducing factors of BP. However, large sample studies concerning BP associated with antipsychotics, as well as with specific mental disorders, are still lacking. Our review retrieved a few clinical studies and case reports on the topic, producing controversial results. We report for the first time a bipolar patient case presenting BP following five-month therapy with risperidone long-acting injectable (LAI). We hypothesize that the dermatological event is associated with the medication administered. The issue emerged during psychiatric consultation and was confirmed by histological examination, direct and indirect immunofluorescence studies, plus positive plasma and cutaneous BP180 and BP230 IgG. Neurodegeneration or neuroinflammation might represent a primary process leading to a cross-reactive immune response between neural and cutaneous antigens and contributing to self-tolerance failure. Furthermore, the time sequence of the shared biological mechanisms leading to clinical manifestations of the neuropsychiatric disorder and BP remains undefined. BP comorbid with bipolar disorder might occasionally represent a serious health risk and affect patients’ physical and psychosocial quality of life. Thus, clinicians treating psychiatric patients should consider BP as a possible adverse effect of psychotropic medications
Role of Albuminuria in Detecting Cardio-Renal Risk and Outcome in Diabetic Subjects
The clinical significance of albuminuria in diabetic subjects and the impact of its reduction
on the main cardiorenal outcomes by different drug classes are among the most interesting research
focuses of recent years. Although nephrologists and cardiologists have been paying attention to the
study of proteinuria for years, currently among diabetics, increased urine albumin excretion
ascertains the highest cardio-renal risk. In fact, diabetes is a condition by itself associated with a
high-risk of both micro/macrovascular complications. Moreover, proteinuria reduction in diabetic
subjects by several treatments lowers both renal and cardiovascular disease progression. The 2019
joint ESC-EASD guidelines on diabetes, prediabetes and cardiovascular (CV) disease assign to
proteinuria a crucial role in defining CV risk level in the diabetic patient. In fact, proteinuria by itself
allows the diabetic patient to be staged at very high CV risk, thus affecting the choice of antihyperglycemic
drug class. The purpose of this review is to present a clear update on the role of
albuminuria as a cardio-renal risk marker, starting from pathophysiological mechanisms in support
of this role. Besides this, we will show the prognostic value in observational studies, as well as
randomized clinical trials (RCTs) demonstrating the potential improvement of cardio-renal
outcomes in diabetic patients by reducing proteinuria
Can Metformin Exert as an Active Drug on Endothelial Dysfunction in Diabetic Subjects?
Abstract: Cardiovascular mortality is a major cause of death among in type 2 diabetes (T2DM).
Endothelial dysfunction (ED) is a well-known important risk factor for the development of diabetes
cardiovascular complications. Therefore, the prevention of diabetic macroangiopathies by preserving
endothelial function represents a major therapeutic concern for all National Health Systems.
Several complex mechanisms support ED in diabetic patients, frequently cross-talking each other:
uncoupling of eNOS with impaired endothelium-dependent vascular response, increased ROS production,
mitochondrial dysfunction, activation of polyol pathway, generation of advanced glycation
end-products (AGEs), activation of protein kinase C (PKC), endothelial inflammation, endothelial
apoptosis and senescence, and dysregulation of microRNAs (miRNAs). Metformin is a milestone
in T2DM treatment. To date, according to most recent EASD/ADA guidelines, it still represents
the first-choice drug in these patients. Intriguingly, several extraglycemic effects of metformin have
been recently observed, among which large preclinical and clinical evidence support metformin’s
efficacy against ED in T2DM. Metformin seems effective thanks to its favorable action on all the
aforementioned pathophysiological ED mechanisms. AMPK pharmacological activation plays a key
role, with metformin inhibiting inflammation and improving ED. Therefore, aim of this review is
to assess metformin’s beneficial effects on endothelial dysfunction in T2DM, which could preempt
development of atherosclerosis
Left bundle branch pacing and cardiac remodeling in HF patients with type 2 diabetes mellitus: epigenetic pathways and clinical outcomes
BackgroundLeft bundle branch (LBB) pacing could achieve cardiac resynchronization therapy (CRT) in patients who cannot be resynchronized via the placement of the left ventricle (LV) lead into the coronary sinus. LBB pacing could improve cardiovascular outcomes in heart failure (HF) patients with LBB block who are affected by type 2 diabetes mellitus (T2DM).Study hypothesisLBB pacing could increase the number of CRT responders and lead to the best clinical outcomes in HF patients with T2DM, inducing cardiac remodeling and improving left ventricle ejection fraction (LVEF) via microRNA (miR) modulation.MethodsIn a multicenter observational study, we enrolled 334 HF patients with LBB block and an indication to receive LBB pacing for CRT. In these patients, we evaluated the CRT responder rate, clinical outcomes, and miR expression at 1 year of follow-up.ResultsAt 1 year of follow-up, we had 223 responders (66.8%), 132 hospitalizations for HF (39.5%), 24 cardiac deaths (7.2%), and 37 all-cause deaths (11.1%), with a higher rate of HF hospitalizations (77 (69.4%) vs 55 (24.7%), p < 0.05), and cardiac deaths (13 (11.7% vs 11 (4.9%), p < 0.05) in non-responders vs responders. At the end of follow-up, we found the lowest expression of miR-26, miR-29, miR-30, miR-92, and miR-145 in LBB-pacing non-responders vs responders (p < 0.05), and a direct correlation between miR-30 (0.340, [0.833–1.915]; p 0.001), the 6-minute-walking test (6MWT; 0.168, [0.008–0.060]; p 0.011), angiotensin-receptor-neprilysin inhibitors (ARNI; 0.157, [0.183–4.877]; p 0.035), sodium-glucose-transporter-2 inhibitors (0.245, [2.242–7.283]; p 0.001), and LVEF improvements. C reactive protein (CRP) inversely correlated with LVEF improvement (−0.220, [-(0.066–0.263)]; p 0.001). ARNI (1.373, CI 95% [1.007–1.872], p 0.045), miR-30 (2.713, CI 95% [1.543–4.769], p 0.001), and 6MWT (1.288, CI 95% [1.084–1.998], p 0.001) were predictors of LBB pacing responders at 1 year of follow-up.ConclusionLBB-pacing responders evidenced miR modulation, which was linked to significant improvement of the cardiac pump. Specifically, miR-30 was linked to cardiac pump improvement and predicted responders at 1 year of follow-up in patients with T2DM
Identification of Altered miRNAs in Cerumen of Dogs Affected by Otitis Externa
Otitis externa is one of the most common diseases in dogs. It is associated with bacteria and yeast, which are regarded as secondary causes. Cerumen is a biological substance playing an important role in the protection of ear skin. The involvement of cerumen in immune defense is poorly understood. MicroRNAs can modulate the host immune response and can provide promising biomarkers for several inflammatory and infectious disorder diagnosis. The aims of this study were to profile the cerumen miRNA signature associated with otitis externa in dogs, integrate miRNAs to their target genes related to immune functions, and investigate their potential use as biomarkers. Cerumen was collected from healthy and otitis affected dogs and the expression of miRNAs was profiled by Next Generation Sequencing; the validation of the altered miRNAs was performed using RT-qPCR. The potential ability of miRNAs to modulate immune-related genes was investigated using bioinformatics tools. The results pointed out that 32 miRNAs, of which 14 were up- and 18 down-regulated, were differentially expressed in healthy vs. otitis-affected dogs. These results were verified by RT-qPCR. To assess the diagnostic value of miRNAs, ROC analysis was carried out, highlighting that 4 miRNAs are potential biomarkers to discriminate otitis-affected dogs. Bioinformatics showed that cerumen miRNAs may be involved in the modulation of host immune response. In conclusion, we have demonstrated for the first time that miRNAs can be efficiently extracted and quantified from cerumen, that their profile changes between healthy and otitis affected dogs, and that they may serve as potential biomarkers. Further studies are necessary to confirm their diagnostic value and to investigate their interaction with immune-related genes
Efficacy and durability of multifactorial intervention on mortality and MACEs:a randomized clinical trial in type-2 diabetic kidney disease
Background: Multiple modifiable risk factors for late complications in patients with diabetic kidney disease (DKD), including hyperglycemia, hypertension and dyslipidemia, increase the risk of a poor outcome. DKD is associated with a very high cardiovascular risk, which requires simultaneous treatment of these risk factors by implementing an intensified multifactorial treatment approach. However, the efficacy of a multifactorial intervention on major fatal/non-fatal cardiovascular events (MACEs) in DKD patients has been poorly investigated. Methods: Nephropathy in Diabetes type 2 (NID-2) study is a multicentre, cluster-randomized, open-label clinical trial enrolling 395 DKD patients with albuminuria, diabetic retinopathy (DR) and negative history of CV events in 14 Italian diabetology clinics. Centres were randomly assigned to either Standard-of-Care (SoC) (n = 188) or multifactorial intensive therapy (MT, n = 207) of main cardiovascular risk factors (blood pressure 40/50 mg/dL for men/women and < 175 mg/dL, respectively). Primary endpoint was MACEs occurrence by end of follow-up phase. Secondary endpoints included single components of primary endpoint and all-cause death. Results: At the end of intervention period (median 3.84 and 3.40 years in MT and SoC group, respectively), targets achievement was significantly higher in MT. During 13.0 years (IQR 12.4–13.3) of follow-up, 262 MACEs were recorded (116 in MT vs. 146 in SoC). The adjusted Cox shared-frailty model demonstrated 53% lower risk of MACEs in MT arm (adjusted HR 0.47, 95%CI 0.30–0.74, P = 0.001). Similarly, all-cause death risk was 47% lower (adjusted HR 0.53, 95%CI 0.29–0.93, P = 0.027). Conclusion: MT induces a remarkable benefit on the risk of MACEs and mortality in high-risk DKD patients. Clinical Trial Registration ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT0053592
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