BsmI (rs1544410) and FokI (rs2228570) vitamin D receptor polymorphisms, smoking, and body mass index as risk factors of cutaneous malignant melanoma in northeast Italy

Objective: To investigate whether vitamin D receptor gene (VDR) BsmI-rs1544410 and FokI-rs2228570 polymorphisms, smoking duration, and body mass index (BMI) are risk factors for cutaneous melanoma, especially metastatic melanoma. Methods: We studied 120 cutaneous melanoma cases [68 stage I and II non-metastatic melanoma (NMetM) patients, plus 52 Stage III and IV metastatic melanoma (MetM) patients], and 120 matching healthy controls from northeast Italy. VDR polymorphisms were measured by restriction fragment length polymorphism analysis. Absence or presence of BsmI and FokI restriction sites was denoted by \u201cB\u201d and \u201cF\u201d or by \u201cb\u201d and \u201cf,\u201d respectively. Results: VDR-BsmI bb genotype was more frequent among MetM (32.7%) than among NMetM cases (13.2%), with odds ratio (OR)=3.18. Comparison of all melanoma patients vs healthy controls showed that the following biomarkers were at risk: 6520 years of smoking (OR=2.43); 6520 years of smoking combined with bb (OR=4.78), Bb+bb (OR=2.30), Ff (OR=3.04), and Ff+ff (OR=3.08); obesity (BMI>30 kg/m2 ) alone (OR=3.54); and obesity combined with Bb+bb (OR=3.52), Ff (OR=4.78), and Ff+ff (OR=6.56). Comparison of MetM vs NMetM patients revealed that the following biomarkers were at risk: 6520 years of smoking (OR=2.39), 6520 years of smoking combined with bb (OR=5.13), Bb+bb (OR=3.07), and Ff+ff (OR=2.66); and obesity combined with Bb+bb (OR=5.27), Ff (OR=6.28), and Ff+ff (OR=9.18). Triple combination of 6520 years of smoking, obesity, and Bb+bb yielded OR=9.65 for melanoma patients vs healthy controls and OR=12.2 for MetM vs. NMetM patients. Conclusions: Risk factors for cutaneous MetM include two VDR polymorphisms combined with smoking duration and obesity. Results suggest gene-environment implications in melanoma susceptibility and severity. Future studies in larger cohorts and in subjects with different genetic background are warranted to extend our findings

peri procedural thrombocytopenia after aortic bioprosthesis implant a systematic review and meta analysis comparison among conventional stentless rapid deployment and transcatheter valves

Abstract Background Thrombocytopenia has been shown to occur soon after surgical biological aortic valve replacement (AVR), and recently reported also after transcatheter valve implantation (TAVI). The mechanism underlying this phenomenon is still unknown, and its clinical impact on the peri-operative outcome has been poorly investigated. Methods A systematic review and a meta-analysis of all available studies reporting data about peri-procedural thrombocytopenia on isolated bio-AVR, comparing rapid-deployment (RDV), stentless (stentless-AVR), and TAVI vs. stented (stented-AVR) valves, have been performed. Results Fifteen trials (2.163 patients) were included in the meta-analysis. Perioperative platelet reduction ranged from 35% to 55% in stented-AVR, from 60% to 77% in stentless-AVR, from 53% to 60% in RDV, and from to 21% to 72% in TAVI (apparently, balloon-expandable valves more frequently associated to thrombocytopenia). Stented-AVR required more red blood cells transfusion than stentless-AVR (P  Conclusions Thrombocytopenia-related major adverse events were mainly reported in TAVI patients, whereas clinically meaningless in surgical patients. Transient peri-procedural thrombocytopenia is common after bio-AVR, regardless of prosthesis's type or implant modality. It should receive appropriate monitoring and focused investigations

Antecedent ACE-inhibition, inflammatory response, and cardiac surgery associated acute kidney injury

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Fecal shedding of thermophilic Campylobacter in a dairy herd producing raw milk for direct human consumption.

Factors affecting the thermophilic Campylobacter fecal shedding in Italian dairy farming conditions have been investigated in a 12-month longitudinal study performed in a dairy farm authorized to sell raw milk in Italy. Fifty animals were randomly selected from 140 adult and young animals, and fecal sampling was performed six times at two month intervals; additionally at each sampling, three trough water samples and two trough feed samples were collected for both adult and young animals. Samples were analyzed by real-time PCR and cultural examination. Overall 33 samples (9.7%) were positive for thermophilic Campylobacter by real-time PCR: 26 out of 280 (9.2%) fecal samples, six out of 36 water points (16.6%) and one of the 24 feed samples (4.2%). Campylobacter jejuni was isolated from 6 out of 280 samples; no other Campylobacter sp. was isolated. A higher but not significant positivity was observed in fecal samples of younger animals (11.33%% versus 6.92% of adult animals) and a higher and significant positivity was observed in water samples collected from the water troughs of young animals. A distinct temporal dynamic trend was observed during the study period for both cows and calves, with two prevalence peaks between November/December and between May/July. Several factors such as calving, housing practices, herd size, management practices forcing together a higher number of animals, variations in feeding or water source, which were previously reported as cause of temporal variation in different farming conditions, could be excluded as cause of the two seasonal peaks in this study. The factors affecting the seasonality of Campylobacter shedding in the dairy herds remain unclear and warrant further investigation. The results of the present study indicate that special attention should be paid to farm hygiene management in farms authorized to produce and sell raw milk with increased surveillance by the authorities in certain periods of the year

Platelets and extra-corporeal membrane oxygenation in adult patients: a systematic review and meta-analysis

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Molecular Determinants of Chronic Venous Disease: A Comprehensive Review

Chronic Venous Disease (CVD) refers to several pathological and hemodynamic alterations of the veins of lower limbs causing a wide range of symptoms and signs with a high prevalence in the general population and with disabling consequences in the most severe forms. The etiology and pathophysiology of CVD is complex and multifactorial, involving genetic, proteomic, and cellular mechanisms that result in changes to the venous structure and functions. Expressions of several genes associated with angiogenesis, vascular development, and the regulation of veins are responsible for the susceptibility to CVD. Current evidence shows that several extracellular matrix alterations (ECM) could be identified and in some cases pharmacologically targeted. This review shows the most up to date information on molecular determinants of CVD in order to provide a complete overview of the current knowledge on this topic. In particular, the article explores the genetic influence, the hormonal influence, ECM imbalance, and histopathology of CVD and the role of endothelial dysfunction in CVD

Immunohistochemical evaluation of vitamin D receptor (VDR) expression in cutaneous melanoma tissues and four VDR gene polymorphisms

ObjectiveVitamin D receptor (VDR) mediates vitamin D activity. We examined whether VDR expression in excised melanoma tissues is associated with VDR gene (VDR) polymorphisms. MethodsWe evaluated VDR protein expression (by monoclonal antibody immunostaining), melanoma characteristics, and carriage of VDR-FokI-rs2228570 (C>T), VDR-BsmI-rs1544410 (G>A), VDR-ApaI-rs7975232 (T>G), and VDR-TaqI-rs731236 (T>C) polymorphisms (by restriction fragment length polymorphism). Absence or presence of restriction site was denoted by a capital or lower letter, respectively: \u201cF\u201d and \u201cf\u201d for FokI, \u201cB\u201d and \u201cb\u201d for BsmI, \u201cA\u201d and \u201ca\u201d for ApaI, and \u201cT\u201d and \u201ct\u201d for TaqI endonuclease. Seventy-four Italian cutaneous primary melanomas (52.1\ub112.7 years old) were studied; 51.4% were Stage I, 21.6% Stage II, 13.5% Stage III, and 13.5% Stage IV melanomas. VDR expression was categorized as follows: 100% positive vs. <100%; over the median 20% (high VDR expression) vs. 6420% (low VDR expression); absence versus presence of VDR-expressing cells. ResultsStage I melanomas, Breslow thickness of <1.00 mm, level II Clark invasion, Aa heterozygous genotype, and AaTT combined genotype were more frequent in melanomas with high versus low VDR expression. Combined genotypes BbAA, bbAa, AATt, BbAATt, and bbAaTT were more frequent in 100% versus <100% VDR-expressing cells. Combined genotype AATT was more frequent in melanomas lacking VDR expression (odds ratio=14.5; P=0.025). VDR expression was not associated with metastasis, ulceration, mitosis >1, regression, tumor-infiltrating lymphocytes, tumoral infiltration of vascular tissues, additional skin and non-skin cancers, and melanoma familiarity. ConclusionsWe highlighted that VDR polymorphisms can affect VDR expression in excised melanoma cells. Low VDR expression in AATT carriers is a new finding that merits further study. VDR expression possibly poses implications for vitamin D supplementation against melanoma. VDR expression and VDR genotype may become precise medicinal tools for melanoma in the future

Aortic aneurysms, chronic kidney disease and metalloproteinases

Metalloproteinases (MPs) are proteolytic enzymes involved in extracellular matrix deposition, regulation of cellular signals of inflammation, proliferation, and apoptosis. Metalloproteinases are classified into three families: Matrix-MPs (MMPs), A-Disintegrin-and-Metalloprotease (ADAMs), and the A-Disintegrin-and-Metalloproteinase-with-Thrombospondin-1-like-Domains (ADAMTS). Previous studies showed that MPs are involved in the development of aortic aneurysms (AA) and, concomitantly, in the onset of chronic kidney disease (CKD). CKD has been, per se, associated with an increased risk for AA. The aim of this review is to examine the pathways that may associate MPs with CKD and AA. Several MMPs, such as MMP-2, -8, -9, and TIMP-1 have been shown to damage the AA wall and to have a toxic effect on renal tubular cells, leading to fibrosis. Similarly, ADAM10 and 17 have been shown to degrade collagen in the AA wall and to worsen kidney function via pro-inflammatory stimuli, the impairment of the Renin-Angiotensin-Aldosterone System, and the degradation of structural proteins. Moreover, MMP-2 and -9 inhibitors reduced aneurysm growth and albuminuria in experimental and human studies. It would be important, in the future, to expand research on MPs from both a prognostic, namely, to refine risk stratification in CKD patients, and a predictive perspective, likely to improve prognosis in response to targeted treatments