Franco Veglio

Università degli Studi di Torino, Torino, Piedmont, Italy

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Publications (312)938.29 Total impact

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    ABSTRACT: Experimental evidence suggests that aldosterone directly contributes to organ damage by promoting cell growth, fibrosis, and inflammation. Based on these premises, this work aimed to assess the glomerular effects of aldosterone, alone and in combination with salt. After undergoing uninephrectomy, 75 rats were allocated to five groups: control, salt diet, aldosterone, aldosterone + salt diet, aldosterone + salt diet and eplerenone, and they were all studied for four weeks. We focused on glomerular structural, functional, and molecular changes, including slit diaphragm components, local renin-angiotensin system activation, as well as pro-oxidative and profibrotic changes. Aldosterone significantly increased systolic blood pressure, led to glomerular hypertrophy, mesangial expansion, and it significantly increased the glomerular permeability to albumin and the albumin excretion rate, indicating the presence of glomerular damage. These effects were worsened by adding salt to aldosterone, while they were reduced by eplerenone. Aldosterone-induced glomerular damage was associated with glomerular angiotensin-converting enzyme (ACE) 2 downregulation, with ACE/ACE2 ratio increase, ANP decrease, as well as with glomerular pro-oxidative and profibrotic changes. Aldosterone damages not only the structure but also the function of the glomerulus. ACE/ACE2 upregulation, ACE2 and ANP downregulation, and pro-oxidative and profibrotic changes are possible mechanisms accounting for aldosterone-induced glomerular injury. © The Author(s) 2015.
    Journal of Renin-Angiotensin-Aldosterone System 08/2015; DOI:10.1177/1470320315595568 · 2.27 Impact Factor
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    ABSTRACT: Co-existing prolactinoma-primary aldosteronism (PA) is infrequently reported. Identify patients with prolactinoma-PA and test the hypothesis that elevated prolactin (PRL) concentrations play a role in PA pathogenesis. Hyperprolactinemia/prolactinoma was diagnosed in PA patients from 2 referral centres (Munich and Turin) and in essential hypertensive (EH) patients from 1 center (Turin). PRL receptor (PRLR) gene expression was determined by microarrays on aldosterone-producing adenomas (APA) and normal adrenals and validated by qPCR. H295R adrenal cells were incubated with 100 nM PRL and gene expression levels were determined by qPCR and aldosterone production was quantified. Seven patients with prolactinoma-PA were identified: 4 out of 584 and 3 out of 442 patients from the Munich and Turin PA cohorts, respectively. A disproportionate number presented with macroprolactinomas (5 out of 7). There were 5 cases of hyperprolactinemia with no cases of macroprolactinoma out of 14,790 patients in a general EH cohort. In a population of PA patients case-control matched 1:3 with EH patients there were 2 cases of hyperprolactinemia out of 270 PA patients and no cases in the EH cohort (n=810). PRLR gene expression was significantly upregulated in APA compared to normal adrenals (1.7-fold and 1.5-fold by microarray and qPCR, respectively). In H295R cells, PRL treatment resulted in 1.3-fold increases in CYP11B2 expression and aldosterone production. Elevated PRL caused by systemic hyperprolactinemia may contribute to the development of PA in those cases where the two entities co-exist.
    The Journal of Clinical Endocrinology and Metabolism 07/2015; DOI:10.1210/JC.2015-2422 · 6.31 Impact Factor
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    ABSTRACT: Pheochromocytomas and paragangliomas (PPGLs) are rare neoplasms often releasing cathecolamines, mainly originating from adrenals but occasionally observed in sympathetic and parasympathetic ganglia, with a genetic base up to 25% of the cases. After radical surgery of these tumors, disease recurrence was believed to be under 10% but recent studies reported a higher rate even after many years. Apart from familiar forms, little evidence exist about predictors of disease relapse, so we aimed to research predictors of recurrence with a retrospective analysis on patients referred to our Centers from 2000. We collected data of patients with diagnosis of PPGL that underwent radical surgery. 76 subjects were recorded (Men/women: 42/34, Age: 45.9 ± 16.2 years) for a mean follow up of 64.9 ± 66.5 months. Genetic test for mutation of known susceptibility genes was performed in 37 cases, resulting positive in 23. 20/76 (26.3%) patients had disease recurrence. These patients were younger (30.7 ± 14.8 vs 51.4 ± 12.9 years; p = 0.000), had higher rate of positive familiarity and genetic mutations (53.3% vs 13.0%; p = 0.002 and 75% vs 14.3%; p = 0.000, respectively), lower rate of abnormal metanephrines levels (27.3% vs 64.4%, p = 0.003), larger tumors (72.4 ± 37.6 vs 45.3 ± 20.2 mm; p = 0.000) and lower biochemical normalization rate (66.6% vs 96.3%, p = 0.004). We also analysed data on follow-up with Kaplan Meier curves, searching for variables associated with cumulative incidence of recurrence by Log Rank test: age at diagnosis < 45 years (p = 0.003), neoplasm dimension > 40 mm (p = 0.009), positive familiarity (p = 0.007) or genetic test (p = 0.000) and lack of biochemical normalization after surgery (p = 0.004) were associated to disease recurrence. Recurrence in PPGLs develops more frequently in young subjects, in patients with mutations in susceptibility genes, larger tumors, normal levels of metanephrines and incomplete normalization of biochemical markers after radical surgery. Patients with these characteristics should be monitored with strictly follow-up.
    Journal of Hypertension 06/2015; 33 Suppl 1 - ESH 2015 Abstract Book:e87. DOI:10.1097/01.hjh.0000467586.58488.d3 · 4.22 Impact Factor
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    ABSTRACT: Renin-angiotensin-aldosterone system (RAAS) is recognized as the main regulatory system of hemodynamics in man, and its derangements have a key role in the development and maintenance of arterial hypertension. Classification of the hypertensive states according to different patterns of renin and aldosterone levels ("RAAS profiling") allows the diagnosis of specific forms of secondary hypertension and may identify distinct hemodynamic subsets in essential hypertension. In this review, we summarize the application of RAAS profiling for the diagnostic assessment of hypertensive patients and discuss how the pathophysiological framework provided by RAAS profiling may guide therapeutic decision-making, especially in the context of uncontrolled hypertension not responding to multi-therapy. © Georg Thieme Verlag KG Stuttgart · New York.
    Hormone and Metabolic Research 06/2015; 47(6):418-26. DOI:10.1055/s-0035-1548868 · 2.04 Impact Factor
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    ABSTRACT: Primary aldosteronism (PA) is the most frequent cause of secondary hypertension responsible for an increased rate of cardiovascular events. According to the Endocrine Society Guidelines, up to 50% of hypertensive patients should be screened for PA, using the aldosterone to renin (or plasma renin activity, PRA) ratio (AARR and ARR, respectively). The automated Diasorin LIAISON® chemiluminescent immunoassay for renin and aldosterone measurement became available and in many laboratories is currently used instead of the classical radioimmunometric PRA and aldosterone assay. Aim of the study was to prospectively compare the diagnostic accuracy of AARR and ARR as screening test for PA and the two aldosterone assays also during confirmatory test in patients with a positive screening test. One hundred patients were screened for PA and 44 patients underwent confirmatory test (either by intravenous saline load or by captopril challenge test). We considered as cut off for the AARR 2.7 (ng/dL/mU/L) and for the ARR 30 (ng/dL/ng/mL/h). All patients positive to one of the two screening test underwent confirmatory test; patients with positive confirmatory test underwent subtype diagnosis by CT scanning and adrenal vein sampling. Seventy three patients were diagnosed as essential hypertensives, 22 had bilateral adrenal hyperplasia and 5 had an aldosterone producing adenomas (APA). The AARR displayed a sensitivity of 78% and a specificity of 100%, whereas the ARR had a sensitivity of 96% and a specificity of 90%. Of the 6/27 PA patients missed by AARR, none resulted to be affected by APA. All PA patients were correctly diagnosed by chemiluminescence at confirmatory test. In the overall sample of 181 measurements available both the correlation for the PRA with renin and for aldosterone in chemiluminescence and radioimmunoassay were highly significant (Rho = 0.66, p < 0.0001 and Rho = 0.80, p < 0.0001, respectively). On ROC curves, the AUC for AARR was 0.905 (95% CI 0.821-0.988) and for ARR 0.947 (95% CI 0.903-0.991) and they were not significantly different. The automated aldosterone and renin chemiluminescent assay is a reliable alternative to the well-established radioimmunometric method, especially for the detection of APA.
    Journal of Hypertension 06/2015; 33 Suppl 1 - ESH 2015 Abstract Book:e121. DOI:10.1097/01.hjh.0000467678.01436.87 · 4.22 Impact Factor
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    ABSTRACT: Adrenal glands removed for unilateral primary aldosteronism (PA) display marked histological heterogeneity. Recently reported somatic mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D can partially account for these differences. In this study we aimed at combining phenotypic and genotypic characteristics, integrating genetic and immunohistochemistry correlates in sporadic PA. Seventy-one adrenal glands have been included in the study and analyzed for mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D. Histological examination and immunohistochemical staining for CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) were performed on aldosterone-producing adenomas (APAs) and adjacent adrenal cortex. In our cohort, the final histopathological diagnosis was multinodular hyperplasia in 22.5% of the patients and single nodule in 77.5%. Forty-five percent of the removed adrenals displayed extra-APA CYP11B2-positive cell nests (B2-CN). Amongst adrenal vein sampling parameters the suppression of contralateral adrenal was more frequent and the lateralization index higher in the subgroup of patients without extra-APA B2-CN compared to the subgroup with extra-APA B2-CN. KCNJ5-mutated APAs were composed mainly of zona fasciculata-like cells with high expression of CYP11B1, while ATP1A1, ATP2B3 and CACNA1D-mutated APAs presented more frequently a zona-glomerulosa-like phenotype with high expression of CYP11B2. We observed a significant inverse correlation between CYP11B2 expression and the size of the nodules and, if CYP11B2 expression was corrected for tumor volume, a significant correlation with plasma aldosterone and aldosterone to renin ratio. Our findings indicate that combination of genotyping and immunohistochemistry improves the final histopatological diagnosis between single nodule and multinodular hyperplasia of the assessed adrenals. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Molecular and Cellular Endocrinology 05/2015; 411. DOI:10.1016/j.mce.2015.04.022 · 4.24 Impact Factor
  • 05/2015; DOI:10.1530/endoabs.37.EP370
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    ABSTRACT: Adrenal vein sampling (AVS) is recognized by Endocrine Society guidelines as the only reliable mean to distinguish between aldosterone producing adenomas and bilateral adrenal hyperplasia, the two most common subtypes of primary aldosteronism (PA). However, despite being the gold-standard procedure, AVS protocols are not standardized and vary widely between centers. The objective of the present study was to assess whether the presence or absence of contralateral adrenal (CL) suppression has an impact on the postoperative clinical and biochemical parameters in patients who underwent unilateral adrenalectomy for PA. The study was retrospectively carried out in eight referral hypertension centers in Italy, Germany and Japan. Case detection and subtype differentiation were performed according to the Japan Endocrine Society and The Endocrine Society guidelines and a total of 234 AVS procedures were included in the study. CL suppression was defined as aldosterone/cortisol non dominant adrenal vein/aldosterone/cortisol peripheral vein less than 1. Overall, 82% of patients displayed CL suppression at AVS, with no statistically significant differences among centers. This percentage was significantly higher in ACTH-stimulated compared with basal procedures (90% vs 77%). The contralateral ratio was inversely correlated with the aldosterone level at diagnosis and, among AVS parameters, with the lateralization index (P < 0.02 and P < 0.01, respectively). To investigate whether the presence of CL suppression was correlated with response to adrenalectomy, we analyzed the CL suppression status with regard to the patient's clinical and biochemical postoperative parameters. No differences were observed between the two groups for the main clinical and biochemical parameters (systolic and diastolic blood pressure, aldosterone, PRA, PRC, K+, number of drugs, reduction of blood pressure levels, and the number of classes of drugs assumed), but patients with CL suppression underwent a significantly larger reduction in aldosterone levels after adrenalectomy. For patients with lateralization indices of greater than 4 (which comprised the great majority of subjects in this study), contralateral suppression should not be required to refer patients to adrenalectomy because it is not associated with a larger blood pressure reduction and might exclude patients from curative surgery.
    05/2015; 33 Suppl 1 - ESH 2015 Abstract Book. DOI:10.1530/endoabs.37.EP66
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    ABSTRACT: The aim of this study was to investigate the short-term blood pressure (BP) variability (BPV) derived from ambulatory blood pressure monitoring (ABPM) in patients with primary aldosteronism (PA), either idiopathic hyperaldosteronism (IHA) or aldosterone-producing adenoma (APA), in comparison with patients with essential hypertension (EH) and normotensive (NT) controls. Thirty patients with PA (16 with IHA and 14 with APA), 30 patients with EH, and 30 NT controls, matched for sex, age, body mass index, and antihypertensive therapy, were studied. The standard deviation (SD) of 24-hour, daytime, and nighttime BP; 24-hour weighted SD of BP; and 24-hour BP average real variability were not different between patients with PA and those with EH (P=not significant). All BPV indices were higher in patients with PA, either IHA or APA subtypes, and patients with EH, compared with NT controls (P<.001 to P<.05). ABPM-derived short-term BPV is increased in patients with PA, and it may represent an additional cardiovascular risk factor in this disease. The role of aldosterone excess in BPV has to be clarified. ©2015 Wiley Periodicals, Inc.
    Journal of Clinical Hypertension 04/2015; DOI:10.1111/jch.12551 · 2.96 Impact Factor
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    ABSTRACT: Primary aldosteronism (PA) is associated with a high rate of cardio- and cerebrovascular complications and metabolic alterations. PA is also recognized as the most frequent, although often unrecognized, secondary form of hypertension. Guidelines have been released to assist clinicians in the diagnostic work-up and subtype differentiation of PA. In this review we discuss and compare the available guidelines in the context of our professional experience and evaluate diagnostic and therapeutic aspects that are still a matter of debate.
    High Blood Pressure & Cardiovascular Prevention 04/2015; DOI:10.1007/s40292-015-0084-5
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    ABSTRACT: Patients with autonomic failure are characterized by orthostatic hypotension, supine hypertension, high blood pressure variability, blunted heart rate variability, and often have a "non-dipping" or "reverse dipping" pattern on 24-h ambulatory blood pressure monitoring. These alterations may lead to cardiovascular and cerebrovascular changes, similar to the target organ damage found in hypertension. Often patients with autonomic failure are on treatment with anti-hypotensive drugs, which may worsen supine hypertension. The aim of this review is to summarize the evidence for cardiac, vascular, renal, and cerebrovascular damage in patients with autonomic failure.
    Clinical Autonomic Research 03/2015; 25(3). DOI:10.1007/s10286-015-0275-0 · 1.86 Impact Factor
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    ABSTRACT: The prevalence of orthostatic hypotension (OH) in hypertensive patients ranges from 3 to 26%. Drugs are a common cause of non-neurogenic OH. In the present study, we retrospectively evaluated the medical records of 9242 patients with essential hypertension referred to our Hypertension Unit. We analysed data on supine and standing blood pressure values, age, sex, severity of hypertension and therapeutic associations of drugs, commonly used in the treatment of hypertension. OH was present in 957 patients (10.4%). Drug combinations including α-blockers, centrally acting drugs, non-dihydropyridine calcium-channel blockers and diuretics were associated with OH. These pharmacological associations must be administered with caution, especially in hypertensive patients at high risk of OH (elderly or with severe and uncontrolled hypertension). Angiotensin-receptor blocker (ARB) seems to be not related with OH and may have a potential protective effect on the development of OH.Journal of Human Hypertension advance online publication, 29 January 2015; doi:10.1038/jhh.2014.130.
    Journal of Human Hypertension 01/2015; DOI:10.1038/jhh.2014.130 · 2.69 Impact Factor
  • European Heart Journal – Cardiovascular Imaging 12/2014; 15 Suppl 2:ii165-ii167. · 2.65 Impact Factor
  • F. Tosello · D. Leone · G. Bruno · A. Ravera · L. Sabia · F. Veglio · A. Milan
    Artery Research 12/2014; 8(4):145. DOI:10.1016/j.artres.2014.09.148
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    ABSTRACT: Essential hypertension arises from the combined effect of genetic and environmental factors. A pharmacogenomics approach could help to identify additional molecular mechanisms involved in its pathogenesis. The aim of SOPHIA study was to identify genetic polymorphisms regulating blood pressure response to the angiotensin II receptor blocker, losartan, with a whole-genome approach. We performed a genome-wide association study on blood pressure response in 372 hypertensives treated with losartan and we looked for replication in two independent samples. We identified a peak of association in CAMK1D gene (rs10752271, effect size -5.5 ± 0.94 mmHg, p = 1.2 × 10(-8)). CAMK1D encodes a protein that belongs to the regulatory pathway involved in aldosterone synthesis. We tested the specificity of rs10752271 for losartan in hypertensives treated with hydrochlorothiazide and we validated it in silico in the GENRES cohort. Using a genome-wide approach, we identified the CAMK1D gene as a novel locus associated with blood pressure response to losartan. CAMK1D gene characterization may represent a useful tool to personalize the treatment of essential hypertension. Original submitted 7 May 2014; Revision submitted 29 July 2014.
    Pharmacogenomics 09/2014; 15(13):1643-52. DOI:10.2217/pgs.14.119 · 3.43 Impact Factor
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    ABSTRACT: Context: Adrenal vein sampling (AVS) is the only reliable means to distinguish between aldosterone producing adenoma and bilateral adrenal hyperplasia, the two most common subtypes of primary aldosteronism (PA). AVS protocols are not standardized and vary widely between centers. Objective: To retrospectively investigate whether the presence of contralateral adrenal (CL) suppression of aldosterone secretion was associated with improved postoperative outcomes in patients who underwent unilateral adrenalectomy for PA. Setting: The study was carried out in 8 different referral centers in Italy, Germany and Japan. Patients: From 585 consecutive AVS in patients with confirmed PA, 234 procedures met the inclusion criteria and were used for the subsequent analyses. Results: Overall, 82% of patients displayed contralateral suppression. This percentage was significantly higher in ACTH stimulated compared to basal procedures (90% vs 77%). CL ratio was inversely correlated with aldosterone level at diagnosis and, amongst AVS parameters, with lateralization index (p=0.02 and 0.01, respectively). The absence of contralateral suppression was not associated with a lower rate of response to adrenalectomy in terms of both clinical and biochemical parameters and patients with CL suppression underwent a significantly larger reduction in aldosterone levels after adrenalectomy. Conclusions: For patients with lateralizing indices of > 4 (which comprised the great majority of subjects in this study), CL suppression should not be required to refer patients to adrenalectomy, since it is not associated with a larger blood pressure reduction after surgery and might exclude patients from curative surgery.
    Journal of Clinical Endocrinology &amp Metabolism 08/2014; 99(11):jc20142345. DOI:10.1210/jc.2014-2345 · 6.31 Impact Factor
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    ABSTRACT: The risk of thoracic aortic dissection is strictly related to the diameter of the ascending aorta. Arterial hypertension represents a major risk factor for the development of aortic dissection and is thought to be directly involved in the pathogenesis of aortic aneurysms. Recent studies have suggested a high prevalence of aortic root enlargement in the hypertensive population, but evidence of a direct link between blood pressure values and size of the aortic root has been inconclusive so far. The aim of the current study was to evaluate prevalence of aortic root dilatation (ARD) in the hypertensive population and to assess the correlates of this condition.
    Journal of Hypertension 06/2014; 32(10). DOI:10.1097/HJH.0000000000000286 · 4.72 Impact Factor
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    ABSTRACT: Patients with autonomic failure experience orthostatic hypotension (OH) often leading to syncope. Arrhythmias may cause severe syncope, characterized by an increased risk of mortality. We report two cases of patients with primary autonomic neuropathy suffering from both severe OH and arrhythmic syncope.
    Clinical Autonomic Research 05/2014; 24(4). DOI:10.1007/s10286-014-0246-x · 1.86 Impact Factor
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    ABSTRACT: Arterial hypertension and cancer are two of the most important causes of mortality in the world; correlations between these two clinical entities are complex and various. Cancer therapy using old (e.g. mitotic spindle poisons) as well as new (e.g. monoclonal antibody) drugs may cause arterial hypertension through different mechanisms; sometimes the increase of blood pressure levels may be responsible for chemotherapy withdrawal. Among newer cancer therapies, drugs interacting with the VEGF (vascular endothelial growth factors) pathways are the most frequently involved in hypertension development. On the other hand, many retrospective studies have suggested a relationship between antihypertensive treatment and risk of cancer, raising vast public concern. The purposes of this brief review have then been to analyse the role of chemotherapy in the pathogenesis of hypertension, to summarize the general rules of arterial hypertension management in this field and finally to evaluate the effects of antihypertensive therapy on cancer disease. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 05/2014; 134(10). DOI:10.1002/ijc.28334 · 5.01 Impact Factor
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    ABSTRACT: Primary aldosteronism comprises subtypes that need different therapeutic strategies. Adrenal vein sampling is recognised by Endocrine Society guidelines as the only reliable way to correctly diagnose the subtype of primary aldosteronism. Unfortunately, despite being the gold-standard procedure, no standardised procedure exists either in terms of performance or interpretation criteria. In this Personal View, we address several questions that clinicians are presented with when considering adrenal vein sampling. For each of these questions we provide responses based on the available evidence, and opinions based on our experience. In particular, we discuss the most appropriate way to prepare the patient, whether adrenal vein sampling can be avoided for some subgroups of patients, the use of ACTH (1-24) during the procedure, the most appropriate criteria for interpretation of adrenal vein cannulation and lateralisation, the use of contralateral suppression, and strategies to improve success rates of adrenal vein sampling in centres with little experience.
    05/2014; 3(4). DOI:10.1016/S2213-8587(14)70069-5

Publication Stats

4k Citations
938.29 Total Impact Points

Institutions

  • 1984–2015
    • Università degli Studi di Torino
      • • Department of Medical Science
      • • Dipartimento di Scienze Cliniche e Biologiche
      Torino, Piedmont, Italy
  • 2009
    • Ospedale San Giovanni Battista, ACISMOM
      Torino, Piedmont, Italy
  • 2007
    • Università Politecnica delle Marche
      • Department of Clinical and Experimental Medicine
      Ancona, The Marches, Italy
  • 2005
    • Ospedali Vito Fazzi
      Lecce, Apulia, Italy
  • 2002
    • University of Mississippi Medical Center
      Jackson, Mississippi, United States
  • 1994–2002
    • University of Camerino
      • Dipartimento di Medicina Sperimentale e Sanità Pubblica
      Camerino, The Marches, Italy
  • 1995–1999
    • Sapienza University of Rome
      • Department of Cardiovascular, Respiratory, Nephrologic and Geriatric Sciences
      Roma, Latium, Italy