Distribution of YLOID in soil-grapevine system (Vitis vinifera L.) as tool for geographical characterization of agro-food products. A two years case study on different grafting combinations

The knowledge of a chemistry relationship between the soil and the agricultural products is an important tool for the quality assessment of food. We studied YLOID (Y, La and lanthanoids), recognized as very useful tracers due their coherent and predictable behavior, to trace and evaluate their distribution from soil to the grape in Vitis vinifera L. Because much of the world’s viticulture is based on grafting, and rootstocks have proved affect vine growth, yield, fruit and wine quality, we carried out experimental trials to analyse the YLOID distribution of two different red cultivars, grafted onto six different rootstocks, on the same soil. The YLOID amounts, the relationship Heavy vs Light YLOID and the pattern of YLOID were calculated. The results showed that the different grafting combinations were not able to induce significant differences in YLOID uptake from the soil maintaining the same fingerprint (with the exception of Eu)

the study of familial hypercholesterolemia in italy a narrative review

Abstract In this review we outline our experience in the clinical and molecular diagnosis of familial hypercholesterolemia (FH), built up over more than three decades. We started our work by selecting FH patients on the basis of stringent clinical criteria, including extensive family studies. In most patients we confirmed the clinical diagnosis by showing a reduced LDLR activity in skin fibroblasts. After the isolation of LDLR cDNA and the characterization of the corresponding gene by the Dallas group, we started a systematic molecular investigation of our patients first using Southern blotting, and, subsequently Sanger sequencing. Up to now we have been able to identify 260 mutations of LDLR gene in more than 1000 genotyped FH patients, including 68 homozygotes. During this survey we identified 13 mutation clusters located in different geographical districts, which gave us the chance to compare the phenotype of patients carrying the most common mutations. We also found that mutations in APOB and PCSK9 genes were a rare cause of FH in our cohort. Despite our efforts, we failed to identify mutations in candidate genes in ∼20% of cases of definite FH. An exome-wide study, conducted within the context of an international collaboration, excluded the presence of other major genes in our unexplained FH cases. Recently, we have adopted sequencing technology of the next generation (NGS) with the parallel sequencing of a panel of FH targeted genes as a way of obtaining a more comprehensive picture of the gene variants potentially involved in the disease

Testing the Short-Term Efficacy of a Lipid-Lowering Nutraceutical in the Setting of Clinical Practice: A Multicenter Study

The main guidelines for cardiovascular disease prevention suggest that nutraceuticals could be an efficacious tool to improve lipid pattern. Our aim was to carry out a clinical trial comparing the metabolic effects of a combined nutraceutical containing both red yeast rice and polyunsaturated fatty acids (PUFAs) and a phytosterol-based approach in a setting of clinical practice. This was a multicenter open study with parallel control. We consecutively enrolled 107 pharmacologically untreated subjects affected by primary polygenic hypercholesterolemia and metabolic syndrome, assigned to 8-week treatment with a combined treatment with red yeast rice (Dif1Stat\uc2\uae, including 5mg monacolin K) and 610mg PUFAs. A parallel group of 30 subjects with similar characteristics was treated with phytosterols 1600mg/die. In the combined nutraceutical group, compared with the baseline level, we observed a significant decrease in total cholesterol (TC; -42.50\uc2\ub118.1mg/dL), low-density lipoprotein cholesterol (LDL-C; -37.6\uc2\ub113.6mg/dL), triglycerides (TG; -19.8\uc2\ub125.1mg/dL), and non-HDL-C (-43.1\uc2\ub117.7mg/dL) (all P<.001). In the phytosterol-treated group, compared to the baseline level, we observed a significant decrease in TC (-13.7\uc2\ub14.3mg/dL), LDL-C (-17.6\uc2\ub18.5mg/dL), and non-HDL-C (-14.1\uc2\ub15.6mg/dL) (all P<.001). When comparing the combined nutraceutical effect with that of phytosterols, we observed that the combined nutraceutical intake was associated with a significantly higher decrease in TC, LDL-C, TG, and non-HDL-C (all P<.001). In the short term, a combined nutraceutical containing red yeast rice and PUFAs is well tolerated and efficacious in reducing plasma lipid levels in subjects affected by primary polygenic hypercholesterolemia and metabolic syndrome

A "de novo" mutation of the LDL-receptor gene as the cause of familial hypercholesterolemia

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APOE MODENA : A NOVEL APOE MUTANT CAUSING LIPOPROTEIN GLOMERULOPATHY

Lipoprotein glomerulopathy (LPG) is a rare disease characterized by laminated lipid thrombi in the lumina of dilated glomerular capillaries. Apolipoproteins E and B can be demonstrated in these lipid deposits. The plasma lipid profile of LPG patients is similar to that of dysbetalipoproteinemia with elevated IDL and ApoE. Patients often present nephrotic proteinuria but their lipid profile differs from that of nephrotic syndrome secondary to other kidney diseases. LPG has been mainly reported in Japanese and Chinese subjects, associated with novel mutations in APOE gene encoding ApoE. We have identified LPG in an Italian women who at the age of 47 was found to have a combined hyperlipidemia (TC 376 and TG 306 mg/dl) and subsequently developed proteinuria in the nephrotic range. Renal biopsy demonstrated lipoprotein thrombi in glomerular capillaries suggesting LPG. The sequence of APOE gene showed that the patient was: i) homozygous for \uf0652 allele [Cys112 and Cys158 in the mature protein] and ii) heterozygous for a novel mutation in exon 4: c.502 C>T [Arg 150>Cys in the mature protein]. Since the mutant ApoE has a new cysteine residue it is likely that it forms a disulfide bridge with the other Cys residues of the E2 isoforms, resulting in ApoE polymerization (dominant negative effect). This is probably the cause of both dyslipidemia and lipid thrombi in the glomerular capillaries. In view of the poor response of plasma lipids and renal histology and function to statin treatment, the patient started lipid-apheresis with reduction of both dyslipidemia and proteinuria

Alternating Hemiplegia of Childhood: Pharmacological treatment of 30 Italian patients

Background Alternating Hemiplegia of Childhood (AHC) is a severe disorder. Several drugs have been administered as prophylaxis for paroxysmal attacks, however, no therapy is completely effective. Methods Our aim is to review the pharmacological data related to the prophylactic and acute treatment of a cohort of 30 patients (16&nbsp;M, 14&nbsp;F, age range 5\u201342&nbsp;years) and to correlate them with the clinical and genetic data collected through the Italian Biobank and Clinical Registry for AHC. Results Flunarizine was the most commonly used long-term treatment in the cohort; it reduced duration and frequency of attacks in 50% of patients and decreased intensity in 32.1%. In younger patients, flunarizine seemed significantly more effective in reducing intensity. We found no correlation between the effectiveness of flunarizine and genotype, or between developmental outcome and duration of treatment. In particular, 3 of our patients affected by E815K mutation presented rapid neurological deterioration despite ongoing treatment. Among the other administered prophylactic therapies, few proved to be effective (benzodiazepines, niaprazine, acetazolamide, melatonin, olanzapine, ketogenic diet). No clear rationale exists regarding their use, but these therapies may work by reducing the triggering factors. Conclusions The presented data are retrospective, but they are aimed at filling a gap given the rarity of the disease and the lack of randomized and controlled studies. Besides their usefulness in clarifying the pathophysiology of the disease, prospective studies involving larger cohorts of ATP1A3 mutated AHC patients are needed to provide a rationale for testing other molecules

Lipoprotein glomerulopathy associated with a mutation in apolipoprotein e

Lipoprotein glomerulopathy is a pathological condition characterized by lipid accumulation in the glomerular capillaries that has been associated with the presence of rare mutants of apolipoprotein E (ApoE). We describe a 51-year-old Italian patient presenting Type III hyperlipidemia and proteinuria in whom renal biopsy showed capillary ectasia and intraluminal lipid deposits, suggesting the diagnosis of lipoprotein glomerulopathy. The patient, who had elevated plasma ApoE level, was found to be heterozygous for a mutation in ApoE (Arg150Cys), designated apoEMODENA. This mutation induces the formation of ApoE dimers that are detectable under non-reducing conditions. Treatment with hypolipidemic drugs did not result in a complete remission of the proteinuria and was accompanied by a slow but progressive worsening of renal function with the persistence of intracapillary lipid thrombi. The introduction of low-density lipoprotein aphaeresis combined with a more aggressive lipid lowering and antihypertensive therapy resulted in the remission of proteinuria and a substantial improvement of renal function. Switching from low-density lipoprotein aphaeresis to plasma filtration did not result in an equivalent control of renal damage. The patient died of intracranial hemorrhage during an acute episode of malignant hypertension

A complex phenotype in a child with familial HDL deficiency due to a novel frameshift mutation in APOA1 gene (apoA-IGuastalla)

Background We describe a kindred with high-density lipoprotein (HDL) deficiency due to APOA1 g ene mutation in which comorbidities affected the phenotypic expression of the disorder. Methods An overweight boy with hypertriglyceridemia (HTG) and HDL deficiency (HDL cholesterol 0.39 mmol/L, apoA-I 40 mg/dL) was investigated. We sequenced the candidate genes for HTG ( LPL, APOC2 , APOA5, GPIHBP1, LMF1 ) and HDL deficiency ( LCAT, ABCA1 and APOA1 ), analyzed HDL subpopulations, measured cholesterol efflux capacity (CEC) of sera and constructed a model of the mutant apoA-I. Results No mutations in HTG-related genes, ABCA1 and LCAT were found. APOA1 sequence showed that the proband, his mother and maternal grandfather were heterozygous of a novel frameshift mutation (c.546_547delGC), which generated a truncated protein (p.[L159Afs*20]) containing 177 amino acids with an abnormal C-terminal tail of 19 amino acids. Trace amounts of this protein were detectable in plasma. Mutation carriers had reduced levels of LpA-I, preβ-HDL and large HDL and no detectable HDL-2 in their plasma; their sera had a reduced CEC specifically the ABCA1-mediated CEC. Metabolic syndrome in the proband explains the extremely low HDL cholesterol level (0.31 mmol/L), which was half of that found in the other carriers. The proband's mother and grandfather, both presenting low plasma low-density lipoprotein cholesterol, were carriers of the β-thalassemic trait, a condition known to be associated with a reduced low-density lipoprotein cholesterol and a reduced prevalence of cardiovascular disease. This trait might have delayed the development of atherosclerosis related to HDL deficiency. Conclusions In these heterozygotes for apoA-I truncation, the metabolic syndrome has deleterious effect on HDL system, whereas β-thalassemia trait may delay the onset of cardiovascular disease

Alternating Hemiplegia of Childhood in a Child Harboring a Novel TBC1D24 Mutation: Case Report and Literature Review

AbstractAlternating Hemiplegia of Childhood (AHC) is a rare neurological disease characterized by early-onset recurrent paroxysmal events and persistent neurological deficits. TBC1D24 gene variants have been associated with a phenotypic spectrum having epilepsy as the main clinical manifestation. Herein, we report the case of a child affected by developmental delay, polymorphic seizures, and nonepileptic episodes characterized by hemiplegia or bilateral plegia, pallor, hypotonia, and dystonic postures without loss of consciousness that resolved with sleep. Noteworthy, the patient fulfills all the diagnostic criteria for AHC. An epilepsy gene panel revealed a novel TBC1D24 mutation. This variant may be considered a PM5, according to the American College of Medical Genetics and Genomics guidelines. TBC1D24 gene variants are associated with various clinical features, and increasing data confirms the association with permanent and paroxysmal movement disorders. Our report suggests that the TBC1D24 molecular analysis could be considered in the diagnostic workup of AHC patients

An integrated approach to the evaluation of patients with asymptomatic or minimally symptomatic hyperCKemia

INTRODUCTION/AIMS: Currently, there are no straightforward guidelines for the clinical and diagnostic management of hyperCKemia, a frequent and nonspecific presentation in muscle diseases. Therefore, we aimed to describe our diagnostic workflow for evaluating patients with this condition. METHODS: We selected 83 asymptomatic or minimally symptomatic patients with persistent hyperCKemia for participation in this Italian multicenter study. Patients with facial involvement and distal or congenital myopathies were excluded, as were patients with suspected inflammatory myopathies or predominant respiratory or cardiac involvement. All patients underwent a neurological examination and nerve conduction and electromyography studies. The first step of the investigation included a screening for Pompe disease. We then evaluated the patients for myotonic dystrophy type II–related CCTG expansion and excluded patients with copy number variations in the DMD gene. Subsequently, the undiagnosed patients were investigated using a target gene panel that included 20 genes associated with isolated hyperCKemia. RESULTS: Using this approach, we established a definitive diagnosis in one third of the patients. The detection rate was higher in patients with severe hyperCKemia and abnormal electromyographic findings. DISCUSSION: We have described our diagnostic workflow for isolated hyperCKemia, which is based on electrodiagnostic data, biochemical screening, and first‐line genetic investigations, followed by successive targeted sequencing panels. Both clinical signs and electromyographic abnormalities are associated with increased diagnostic yields