Correction: A european spectrum of pharmacogenomic biomarkers: Implications for clinical pharmacogenomics (PLoS ONE (2016) 11:9 (e0162866) DOI: 10.1371/journal.pone.0162866)

The thirty-Third author's name is spelled incorrectly. The correct name is: Jadranka Sertić

A European spectrum of pharmacogenomic biomarkers: Implications for clinical pharmacogenomics

Pharmacogenomics aims to correlate inter-individual differences of drug efficacy and/or toxicity with the underlying genetic composition, particularly in genes encoding for protein factors and enzymes involved in drug metabolism and transport. In several European populations, particularly in countries with lower income, information related to the prevalence of pharmacogenomic biomarkers is incomplete or lacking. Here, we have implemented the microattribution approach to assess the pharmacogenomic biomarkers allelic spectrum in 18 European populations, mostly from developing European countries, by analyzing 1,931 pharmacogenomics biomarkers in 231 genes. Our data show significant interpopulation pharmacogenomic biomarker allele frequency differences, particularly in 7 clinically actionable pharmacogenomic biomarkers in 7 European populations, affecting drug efficacy and/or toxicity of 51 medication treatment modalities. These data also reflect on the differences observed in the prevalence of high-risk genotypes in these populations, as far as common markers in the CYP2C9, CYP2C19, CYP3A5, VKORC1, SLCO1B1 and TPMT pharmacogenes are concerned. Also, our data demonstrate notable differences in predicted genotype-based warfarin dosing among these populations. Our findings can be exploited not only to develop guidelines for medical prioritization, but most importantly to facilitate integration of pharmacogenomics and to support pre-emptive pharmacogenomic testing. This may subsequently contribute towards significant cost-savings in the overall healthcare expenditure in the participating countries, where pharmacogenomics implementation proves to be cost-effective

The size of juxtaluminal hypoechoic area in ultrasound images of asymptomatic carotid plaques predicts the occurrence of stroke

Objective: To test the hypothesis that the size of a juxtaluminal black (hypoechoic) area (JBA) in ultrasound images of asymptomatic carotid artery plaques predicts future ipsilateral ischemic stroke. Methods: A JBA was defined as an area of pixels with a grayscale value <25 adjacent to the lumen without a visible echogenic cap after image normalization. The size of a JBA was measured in the carotid plaque images of 1121 patients with asymptomatic carotid stenosis 50% to 99% in relation to the bulb (Asymptomatic Carotid Stenosis and Risk of Stroke study); the patients were followed for up to 8 years. Results: The JBA had a linear association with future stroke rate. The area under the receiver-operating characteristic curve was 0.816. Using Kaplan-Meier curves, the mean annual stroke rate was 0.4% in 706 patients with a JBA <4 mm 2, 1.4% in 171 patients with a JBA 4 to 8 mm2, 3.2% in 46 patients with a JBA 8 to 10 mm2, and 5% in 198 patients with a JBA >10 mm2 (P <.001). In a Cox model with ipsilateral ischemic events (amaurosis fugax, transient ischemic attack [TIA], or stroke) as the dependent variable, the JBA (<4 mm2, 4-8 mm2, >8 mm2) was still significant after adjusting for other plaque features known to be associated with increased risk, including stenosis, grayscale median, presence of discrete white areas without acoustic shadowing indicating neovascularization, plaque area, and history of contralateral TIA or stroke. Plaque area and grayscale median were not significant. Using the significant variables (stenosis, discrete white areas without acoustic shadowing, JBA, and history of contralateral TIA or stroke), this model predicted the annual risk of stroke for each patient (range, 0.1%-10.0%). The average annual stroke risk was <1% in 734 patients, 1% to 1.9% in 94 patients, 2% to 3.9% in 134 patients, 4% to 5.9% in 125 patients, and 6% to 10% in 34 patients. Conclusions: The size of a JBA is linearly related to the risk of stroke and can be used in risk stratification models. These findings need to be confirmed in future prospective studies or in the medical arm of randomized controlled studies in the presence of optimal medical therapy. In the meantime, the JBA may be used to select asymptomatic patients at high stroke risk for carotid endarterectomy and spare patients at low risk from an unnecessary operation

Oxidative stability of lipids and cholesterol in salame Milano, coppa and Parma ham: dietary supplementation with vitamin E and oleic acid

An investigation has been carried out on the e ect of dietary supplementation with vitamin E and oleic acid on oxidative stability of Italian representative pork products. Fatty acid composition of deposited fat was modi®ed in the oil supplemented groups with negative e ects on fat ®rmness. Oil supplementation signi®cantly increased vitamin E content of muscles, as well. Oxidative stability of fat, evaluated by TBARS and cholesterol oxides, has not shown signi®cant di erences between dietary treatments but, although the di erences were not signi®cant, the tendency was su ciently clear, especially in salame Milano, towards a lower oxidation level in vitamin E enriched meat. Cholesterol oxidation was found to vary in general around 0.1% of total cholesterol and the only cholesterol oxides observed were 7b-hydroxycholesterol, 5,6a-epoxycholesterol and 7-ketocholesterol. Aldehydes content and dis- tribution appeared to be linked, ®rstly, to the speci®c processing technology of the product and, secondly, to the changed fatty acid composition

Colour stability and vitamin E content of fresh and processed pork

The e ect of increasing muscular content of vitamin E on colour intensity and stability of pork (both fresh and processed) was studied by feeding manipulation. Fresh pork was represented by loin chops and processed pork was represented by a dry cured fermented sausage (salame Milano) and raw cured ham (Parma ham). Dietary vitamin E was increased by feeding the animals with sun¯ower oil and -tocopheryl acetate at 100 and 200 ppm. Chops were packed in oxygen-permeable ®lm and in a protective atmosphere (80% O2 and 20% CO2) whereas salame Milano and Parma ham were packed under vacuum and in a protective atmosphere (85% N2 and 15% CO2). No di erences in colour intensity or type were observed in relation to vitamin E content. Colour stability tests suggested, on the other hand, that higher vitamin E contents could be associated with slower myoglobin oxi- dation rates in fresh chops packed in a protective atmosphere. No e ect of vitamin E on colour stability was observed in salame, probably because of the soft fat induced by sun¯ower oil. Signi®cant di erences among dietary groups were also not observed in Parma ham

Prodotti di salumeria crudi (Prosciutto, Salame, Coppa) e ossidazione lipidica

É stata condotta un'indagine sui processi ossidativi che possono interessare la frazione lipidica di alcuni tra i più rapprrsentativi prodotti di salumeria crudi: il salame, la coppa e il prosciutto. Di tali prodotti sono stati determinati la composizione centesimale, l'azoto non proteico, il sale, il numero di perossidi, il valore di TBARS, la quantità di aldeidi volatili, il contenuto di colesterolo totale e gli ossidi del colesterolo. I risultati della sperimentazione hanno dimostrato livelli di ossidazione primaria (numero di perossidi) e secondaria (TRARS) molto bassi nei prosciutti e leggermente più alti, ma sempre molto contenuti nei salami. Nelle coppe i valori di TBARS sono risultati più bassi che nei salami ma il numero di perossidi era più elevato. La determinazione delle aldeidi ha messo in evidenza una notevole varìabilità tra i canrpioni di uno stesso prodotto, in buona parte da ascrivere al metodo di analisi, mentre le differenze all'interno dei tre prodotti sono apparse in genere non molto marcate. Il contenuto di colesterolo è risultato essere più basso nel prosciutto (70 mg/100g), intermedio nei salami (circa 100mg/100g) e poco più alto nelle coppe (circa 110mg/100g). In tutti e tre i prodotti sono stati osservati solamente tre ossidi del colesterolo: il 7-idrossicolesteroloi, il 7-chetocoleterolo e il 5,6-epossicolesterolo. ll livello medio di colesterolo riscontrato nel corso della sperimentazione varia da 0,06% nel salame a 0,18% nella coppa. ll tipo di ossidi riscontrato e le quantità relative osservate sono discussi in relazione al possibile impatto sulla salute dei consumatori. Viene ampiamente discussa la metodica utilizzata per la determinazione degli ossidi del colesterolo alla luce delle difficoltà analitiche riscontrate

Oil and vitamin E supplementation and colour stability of fresh and processed pork

Oxidation is a major cause of chemical deterioration of food due to its effects on organoleptic qualities such as taste, flavour and colour. Colour type and stability during prolonged exposure to light is a key element of shelf-life Oxidatìon of lipids and myoglobin are strictly related, On the ore hand radicals produced from lipid oxidation appear to accelerate myoglobin oxidation directly or indirectly by weakening muscle reducing systems. On the other hand metmyoglobin and oxymyoglobin appear to be able to catalyse lipid oxidation, the latter probably through hydrogen generated during oxidation. There seems to exist a direct relationship between malonalhdehyde formation and metmyoglobin increase. The research which has been undertaken aimed at studying the effect of increasing muscular content of vitamin E on colour stability of fresh and processed pork

Ischemia-reperfusion of human skeletal muscle during aortoiliac surgery: effects of acetylcarnitine

Our previous study on human skeletal muscle undergoing ischemia and reperfusion has revealed that granulocytes, which infiltrate the muscle tissue in large numbers, play an important role in mediating fibre injuries by producing superoxide anion (O?) which is responsible for membrane lipid peroxidation. In the current study, five patients undergoing aortic reconstructive surgery were given acetyl-carnitine (2 mglkg i.v. plus 1 mglkglmin for 30 min) prior to the induction of ischemia. Muscle biopsies and blood samples were examined: a) after anaesthesia; b) at the end of ischemia; and c) 30 min after reperfusion, with the aim of elucidating whether acetylcarnitine could prevent the infiltration andlor the activation of granulocytes and eventually skeletal muscle injuries. During ischemia and reperfusion complement activation recmited numerous granulocytes into the muscle tissue, but, contrary to the untreated samples, the ability for O2 -generation of these cells remained at low levels and was comparable to that of ischemia even when molecular 02 was reintroduced to the tissue. Accordingly, the morphological changes of the postischemic muscle fibers were substantially reduced when compared to the untreated samples; in fact, the mitochondrial swelling was only moderate and the intramitochondrial dense bodies were small and scarce. The current findings support a positive role of acetyl-carnitine in ameliorating the ischernia-reperfusion (1-R)-induced damage of human skeletal muscle