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OBJECTIVE: Coronary artery disease is one of the first causes of death in the Western world; for this reason, it is essential to identify new, systemic, non-invasive and low-cost cardiovascular risk markers. The acute coronary syndrome includes ST-Elevation Myocardial Infarction (STEMI) and Non-ST-Elevation Myocardial Infarction (NSTEMI), based on ECG findings. We aimed to evaluate Renal Resistive Index (RRI) as a marker of cardiovascular risk and assess the associations with other cardiovascular risk factors (metabolic indexes, mineral metabolism disorders and endothelial dysfunction and atherosclerosis markers) in STEMI and NSTEMI patients. PATIENTS AND METHODS: Clinical, laboratory and instrumental examinations as metabolic and inflammation indexes, markers of atherosclerosis and endothelial dysfunction (renal function, mineral metabolism disorders, inflammation indexes, Intima Media Thickness (IMT), Ankle Brachial Pressure Index, Left Ventricular Mass Index, Relative Wall Thickness) were performed. RESULTS: Eighty-one patients with STEMI and NSTEMI were enrolled. We showed a significant positive correlation between RRI and age (p<0.01), intact parathyroid hormone (p<0.01) and IMT (p<0.01), as well as a significant negative correlation between RRI and body surface area (BSA) (p=0.02), estimated Glomerular Filtration Rate (eGFR) (p<0.01), serum calcium (p<0.01) and 25-hydroxy-vitamin D (p=0.03). Moreover, we found a significant correlation between RRI and male patients (p<0.01), coronary artery disease history (CAD) (p=0.049), hypertension (p=0.025) and left ventricular eccentric hypertrophy (LVEH) (p=0.047). CONCLUSIONS: Our study showed an association between RRI and the main traditional and non-traditional cardiovascular risk factors involved in atherosclerosis pathogenesis, such as age, BSA, hypertension, male sex, CAD history, mineral metabolism disorders and LVEH, in patients with preserved renal function. Moreover, we found a significant correlation between RRI and eGFR, suggesting that RRI could be useful in the evaluation of both renal function and progression of renal damage, even in an early stage with a conserved or only slightly reduced kidney function. We also showed a significant correlation with some markers of systemic atherosclerosis such as IMT and LVEH. For a more precise assessment of prognosis and cardiovascular risk in patients with high cardiovascular mortality, we suggest performing a systematic RRI evaluation, considering the non-invasive nature of the procedure, its reproducibility, easy execution, and low costs. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Resistant hypertension (RH) may be associated with Obstructive Sleep Apnea (OSA), determining a remarkable increase in cardiovascular risk. The aim of the study was to assess the effect of six months with continuous positive airway pressure (CPAP) treatment on blood pressure (BP) values, cardiovascular risk markers, and exercise tolerance in patients with RH and OSA. PATIENTS AND METHODS: Twenty-four patients with RH and OSA were recruited and 24-hour ambulatory BP, intima-media thickness (IMT), flow mediated dilation (FMD), renal resistive index (RRI), and endurance cardiopulmonary exercise testing (CPET) were obtained at enrollment and after 6-month treatment. RESULTS: Significant reduction in clinic systolic and diastolic BP, IMT, and RRI (p = 0.003, p = 0.009, p = 0.020, p = 0.04, respectively) and increase in the left ventricular ejection fraction (p = 0.035) were observed after a 6-month therapy with CPAP. Moreover, improvement in all polysomnographic parameters (number of apneas/hypopneas per hour (p < 0.001), number of episodes of night-time hemoglobin desaturation (ODI) (p = 0.010)), an improvement in Epworth Sleepiness Scale (p < 0.001), as well as in endurance time during constant workload CPET (p = 0.017) were observed too. CONCLUSIONS: CPAP treatment for six months reduces BP and improves cardiovascular risk and exercise tolerance in patients with RH and OSA. An extended cardiovascular assessment, including exercise testing, might be helpful in this population, given the possible reversibility of some endothelial dysfunction and atherosclerotic markers with CPAP treatment, as reported in our study. [ABSTRACT FROM AUTHOR]

Introduction: Cardiovascular (CV) complications are the most frequent cause of morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) patients. In 2017, the Italian Medicines Agency authorised tolvaptan, a vasopressin V2 receptor antagonist, for the treatment of ADPKD, based on the Tolvaptan Phase 3 Efficacy and Safety Study in ADPKD (TEMPO 3: 4), TEMPO 4: 4 and Replicating Evidence of Preserved Renal Function: An Investigation of Tolvaptan Safety and Efficacy (REPRISE) studies., Aim of the Study: The aim of the study was to assess the impact of tolvaptan on CV risk and quality of life, evaluated by nutritional, inflammatory, metabolic, instrumental parameters and psychocognitive tests on ADPKD patients., Methods and Materials: We evaluated 36 patients with ADPKD; 10 patients (7 males, mean age 42.5±7.0 years) treated with tolvaptan and 26 controls (11 males, mean age 36.7±9.1 years). They underwent, at T0, monthly, and at T1 (1 year) clinical, laboratory and instrumental evaluation, in addition to psychocognitive tests., Results: In ADPKD patients treated with tolvaptan, we found at T1, a decrease in carotid intima-- media thickness (p=0.048), epicardial adipose tissue thickness (p=0.002), C-reactive protein (p=0.026), sympathovagal balance during night (p=0.045) and increased flow-mediated dilation (p=0.023) with a reduction in depression (Hamilton and Beck tests, p=0.008 and p=0.002, respectively) compared with controls., Conclusion: These preliminary results suggest that treatment with tolvaptan could improve early atherosclerosis and endothelial dysfunction markers and improve mood in ADPKD patients (probably by acting on endothelial cell and adipocyte V2 receptors)., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Cardiovascular disease is one of the main causes of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Autonomic dysfunction is associated with an increased risk for all cardiovascular events in the general population and can be evaluated with heart rate variability (HRV)., Objective: To evaluate HRV in ADPKD patients with mild hypertension versus hypertensive patients with organ damage and healthy controls (HC)., Materials and Methods: We have enrolled 65 patients: 21 ADPKD patients (10 males), 20 patients with hypertension (14 males), and 24 HC (10 males). Biochemical analysis, clinical evaluation, anthropometric data, intima-media thickness, 24-h ECG Holter recording, and echocardiography were investigated at the time of enrollment., Results: No significant differences in HRV parameters were found between ADPKD with mild hypertension and hypertensive patients with organ damage. The median of HRV variables in time domain as SDNN (global autonomic activity) was significantly lower in ADPKD and hypertensive patients than HC (p < 0.05). In the frequency domain analysis, low frequency (LF), which mainly reflects the sympathetic component, showed higher values in ADPKD and hypertensive patients than HC during the night (p < 0.01). During the night, the sympathovagal balance, LF/high frequency (HF), showed higher values in ADPKD and hypertensive patients than HC (p < 0.0001). Conversely, LF day was lower in ADPKD and hypertensive patients than HC (p < 0.01). HF, which mainly reflects the parasympathetic component, was lower in ADPKD and hypertensive patients during the night than HC (p < 0.0001)., Conclusions: HRV reduction is present in ADPKD patients with mild hypertension in the absence of organ damage. The evaluation of sympathovagal balance can provide novel information on the cardiovascular risk in ADPKD patients in addition to classical risk factors., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Background: Chronic kidney disease (CKD) is a highly prevalent condition. Urologic disorders are known causes of CKD, but often remain undiagnosed and underestimated also for their insidious onset and slow progression. We aimed to evaluate the prevalence of urological unrecognized diseases in CKD patients by uroflowmetry., Methods: We enrolled consecutive stable CKD outpatients. The patients carried out two questionnaires, the International Prostate Symptom Score and Incontinence Questionnaire-Short Form, and they also underwent uroflowmetry, evaluating max flow rate ( Q max ), voiding time and voided volume values., Results: A total of 83 patients (43 males, mean age of 59.8 ± 13.3 years) were enrolled. Our study showed 28 males and 10 females with a significant reduction of Q max (P < 0.001) while 21 females reported a significant increase of Q max (P < 0.001) with a prevalence of 49.5% of functional urological disease. Moreover, we showed a significant association between Q max and creatinine (P = 0.013), estimated glomerular filtration rate (P = 0.029) and voiding volume (P = 0.05). We have not shown significant associations with age (P = 0.215), body mass index (P = 0.793), systolic blood pressure (P = 0.642) or diastolic blood pressure (P = 0.305). Moreover, Pearson's chi-squared test showed a significant association between Q max altered with CKD (χ 2  = 1.885, P = 0.170) and recurrent infection (χ 2  = 8.886, P = 0.012), while we have not shown an association with proteinuria (χ 2  = 0.484, P = 0.785), diabetes (χ 2  = 0.334, P = 0.563) or hypertension (χ 2  = 1.885, P = 0.170)., Conclusions: We showed an elevated prevalence of urological diseases in nephropathic patients; therefore, we suggest to include uroflowmetry in CKD patient assessment, considering the non-invasiveness, repeatability and low cost of examination. Uroflowmetry could be used to identify previously unrecognized urological diseases, which may prevent the onset of CKD or progression to end-stage renal disease and reduce the costs of management.

Background: The number of human immunodeficiency virus (HIV)-infected patients has increased significantly, although the number of deaths due to HIV and acquired immunodeficiency syndrome (AIDS) has dramatically reduced. Highly active antiretroviral therapy (HAART) has increased not only survival but also the risk of deaths caused by other diseases or by long-term side effects of these drugs., Aim: The aim of this study is to evaluate the nephrotoxicity of one of the most common anti-retroviral drugs, tenofovir disoproxil fumarate (TDF)., Materials and Methods: We examined 27 patients with HIV infection (10 women). Patients assumed TDF for a mean period of 8.03 months. Indexes of renal function and serum electrolytes were measured, and glomerular filtration rate was estimated (eGFR). Proteinuria, glycosuria, bicarbonaturia, and phosphaturia were assessed, and renal ultrasound examination was carried out., Results: Acute kidney injury with glycosuria, bicarbonaturia, and phosphaturia was seen in 22 patients. Substantial recovery of renal function occurred in 19 patients., Conclusion: This study highlights that TDF nephrotoxicity is a widely frequent but reversible form of renal damage with preferentially proximal tubular dysfunction. We suggest that all patients at the time of HIV diagnosis should carry out a screening for kidney disease with eGFR assessment, proteinuria, and urine analysis.

Background: Patients with chronic kidney disease (CKD) show a risk of cardiovascular death, which is 10-100 times higher than that in the general population. This increase is not completely explained by the traditional cardiovascular risk factors. Hyperuricemia and hyperhomocysteinemia are highly prevalent in CKD. Patients suffering from these complications present accelerated atherosclerosis, determined mainly from the endothelial dysfunction that carries out a central role in the pathogenesis of cardiovascular diseases., Aim: The hypothesis was that brachial artery flow mediated dilation (FMD) and carotid intima-media thickness (cIMT) evaluation can be considered as early and systemic markers of atherosclerosis and that nontraditional risk factors, such as hyperhomocysteinemia and hyperuricemia, are associated with early endothelial dysfunction and vascular damage in patients suffering from first- and second-stage CKD., Patients and Methods: The study comprised 50 patients, 10 for each CKD stage, and 15 age- and sex-matched healthy controls. We compared the traditional and nontraditional factors for cardiovascular diseases with alterations of vascular reactivity, such as cIMT, and brachial artery FMD, in patients affected by CKD with those in the control group., Results: In our study, hyperuricemia was significantly and independently associated with brachial artery FMD reduction (p = 0.007), while hyperhomocysteinemia was significantly and independently associated with carotid intima-media thickening (p = 0.021) in patients at Stage I and II KDOQI (Kidney Disease Outcomes Quality Initiative)., Conclusions: In our study, we found a progressive increase in the inflammatory indices and endothelial dysfunction at the early stages of CKD. Hyperuricemia and hyperhomocysteinemia were associated with IMT and FMD at Stage I-III KDOQI, and can be used as markers of subclinical atherosclerosis, especially in nephropathic patients with high cardiovascular risk.

Background: Recent studies have demonstrated an unexpected complexity of transcription in eukaryotes. The majority of the genome is transcribed and only a little fraction of these transcripts is annotated as protein coding genes and their splice variants. Indeed, most transcripts are the result of antisense, overlapping and non-coding RNA expression. In this frame, one of the key aims of high throughput transcriptome sequencing is the detection of all RNA species present in the cell and the first crucial step for RNA-seq users is represented by the choice of the strategy for cDNA library construction. The protocols developed so far provide the utilization of the entire library for a single sequencing run with a specific platform., Results: We set up a unique protocol to generate and amplify a strand-specific cDNA library representative of all RNA species that may be implemented with all major platforms currently available on the market (Roche 454, Illumina, ABI/SOLiD). Our method is reproducible, fast, easy-to-perform and even allows to start from low input total RNA. Furthermore, we provide a suitable bioinformatics tool for the analysis of the sequences produced following this protocol., Conclusion: We tested the efficiency of our strategy, showing that our method is platform-independent, thus allowing the simultaneous analysis of the same sample with different NGS technologies, and providing an accurate quantitative and qualitative portrait of complex whole transcriptomes.

Alternative splicing is emerging as a major mechanism for the expansion of the transcriptome and proteome diversity, particularly in human and other vertebrates. However, the proportion of alternative transcripts and proteins actually endowed with functional activity is currently highly debated. We present here a new release of ASPicDB which now provides a unique annotation resource of human protein variants generated by alternative splicing. A total of 256,939 protein variants from 17,191 multi-exon genes have been extensively annotated through state of the art machine learning tools providing information of the protein type (globular and transmembrane), localization, presence of PFAM domains, signal peptides, GPI-anchor propeptides, transmembrane and coiled-coil segments. Furthermore, full-length variants can be now specifically selected based on the annotation of CAGE-tags and polyA signal and/or polyA sites, marking transcription initiation and termination sites, respectively. The retrieval can be carried out at gene, transcript, exon, protein or splice site level allowing the selection of data sets fulfilling one or more features settled by the user. The retrieval interface also enables the selection of protein variants showing specific differences in the annotated features. ASPicDB is available at http://www.caspur.it/ASPicDB/.

Background: Many evidences report that alternative splicing, the mechanism which produces mRNAs and proteins with different structures and functions from the same gene, is altered in cancer cells. Thus, the identification and characterization of cancer-specific splice variants may give large impulse to the discovery of novel diagnostic and prognostic tumour biomarkers, as well as of new targets for more selective and effective therapies., Results: We present here a genome-wide analysis of the alternative splicing pattern of human genes through a computational analysis of normal and cancer-specific ESTs from seventeen anatomical groups, using data available in AspicDB, a database resource for the analysis of alternative splicing in human. By using a statistical methodology, normal and cancer-specific genes, splice sites and cassette exons were predicted in silico. The condition association of some of the novel normal/tumoral cassette exons was experimentally verified by RT-qPCR assays in the same anatomical system where they were predicted. Remarkably, the presence in vivo of the predicted alternative transcripts, specific for the nervous system, was confirmed in patients affected by glioblastoma., Conclusion: This study presents a novel computational methodology for the identification of tumor-associated transcript variants to be used as cancer molecular biomarkers, provides its experimental validation, and reports specific biomarkers for glioblastoma.

p63 belongs to a family of transcription factors, which, while demonstrating striking conservation of functional domains, regulate distinct biological functions. Its principal role is in the regulation of epithelial commitment, differentiation and maintenance programs, during embryogenesis and in adult tissues. The p63 gene has a complex transcriptional pattern, producing two subclasses of N-terminal isoforms (TA and DeltaN) which are alternatively spliced at the C-terminus. Here, we report the identification of two new C-terminus p63 variants, we named p63 delta and epsilon, that increase from 6 to 10 the number of the p63 isoforms. Expression analysis of all p63 variants demonstrates a tissue/cell-type-specific nature of p63 alternative transcript expression, probably related to their different cellular functions. We demonstrate that the new p63 variants as DeltaN isoforms are active as transcription factors as they have nuclear localization and can modulate the expression of p63 target genes. Moreover, we report that, like DeltaNp63alpha, DeltaNp63delta and epsilon sustain cellular proliferation and that their expression decreases during keratinocyte differentiation, suggesting their involvement in this process. Taken together, our results demonstrate the existence of novel p63 proteins whose expression should be considered in future studies on the roles of p63 in the regulation of cellular functions.