Twelve Variants Polygenic Score for Low-Density Lipoprotein Cholesterol Distribution in a Large Cohort of Patients With Clinically Diagnosed Familial Hypercholesterolemia With or Without Causative Mutations

: Background A significant proportion of individuals clinically diagnosed with familial hypercholesterolemia (FH), but without any disease-causing mutation, are likely to have polygenic hypercholesterolemia. We evaluated the distribution of a polygenic risk score, consisting of 12 low-density lipoprotein cholesterol (LDL-C)-raising variants (polygenic LDL-C risk score), in subjects with a clinical diagnosis of FH. Methods and Results Within the Lipid Transport Disorders Italian Genetic Network (LIPIGEN) study, 875 patients who were FH-mutation positive (women, 54.75%; mean age, 42.47±15.00 years) and 644 patients who were FH-mutation negative (women, 54.21%; mean age, 49.73±13.54 years) were evaluated. Patients who were FH-mutation negative had lower mean levels of pretreatment LDL-C than patients who were FH-mutation positive (217.14±55.49 versus 270.52±68.59 mg/dL, P<0.0001). The mean value (±SD) of the polygenic LDL-C risk score was 1.00 (±0.18) in patients who were FH-mutation negative and 0.94 (±0.20) in patients who were FH-mutation positive (P<0.0001). In the receiver operating characteristic analysis, the area under the curve for recognizing subjects characterized by polygenic hypercholesterolemia was 0.59 (95% CI, 0.56-0.62), with sensitivity and specificity being 78% and 36%, respectively, at 0.905 as a cutoff value. Higher mean polygenic LDL-C risk score levels were observed among patients who were FH-mutation negative having pretreatment LDL-C levels in the range of 150 to 350 mg/dL (150-249 mg/dL: 1.01 versus 0.91, P<0.0001; 250-349 mg/dL: 1.02 versus 0.95, P=0.0001). A positive correlation between polygenic LDL-C risk score and pretreatment LDL-C levels was observed among patients with FH independently of the presence of causative mutations. Conclusions This analysis confirms the role of polymorphisms in modulating LDL-C levels, even in patients with genetically confirmed FH. More data are needed to support the use of the polygenic score in routine clinical practice

Somatic (CSS) and differential cell count (DCC) during a lactation period in ass’milk

Hypoallergenic properties of ass&rsquo;s milk protein fractions have been recently con- firmed, allowing ass&rsquo;s milk to be considered as a valid substitute of the available hypoallergenic infant formulas. The objective of this study was to give a further contribution to the knowledge of ass&rsquo;s milk safety and quality characteristics. A new procedure has been developed with a cytospin centrifuge in differential counts of milk somatic cells. Somatic cells count (SCC), differential somatic cells count (DCC) and cultural examinations have been carried out in 62 milk samples collected from 11 asses at three different stages of lactation. Four major cells populations had been identified in ass&rsquo;s milk too: lymphocytes (Ly), monocytes/macrophages (MA), polymorphonuclear neutrophils (PMNL), and epithelial cells (CE). The patterns of these cells have been discussed in comparison with cells found in dairy cows and ewes milk. In conclusion, a reproducible standard procedure has been developed to determine cell count of ass&rsquo;s milk

Effect of olive pomace and extruded linseed on milk yield and fatty acid composition from dairy ewes

Use of extruded linseed (EL) in the diet of dairy ewes is an effective strategy to enrich milk with omega-3 polyunsaturated fatty acids (PUFA n-3) and conjugated linoleic acid (CLA). However, since EL is largely bio- hydrogenated in the rumen, the amount of extruded linseed needed to obtain an effective enrichment of PUFA n-3 in milk fat may often result in an increase of feeding cost. The use of polyphenols in the diet of dairy ruminants has been proposed as strategy to perturb rumen biohydro- genation of dietary PUFA and to increase the passage rate of PUFA omega-3 from the diet to milk. Crude phenolic concentrate (CPC) obtained by membrane filtration of olive vegetation waters to reduce their pollutant charge could be considered a good source of polyphenols, mainly secoridoides derivatives. The aim of this study was to evaluate the effect of the inclusion of linseed and CPC in diets of dairy ewes on milk yield and fatty acid (FA) composition. Twenty pluriparous Comisana ewes were randomly allotted into four groups after a baseline period of three weeks, when the animals received the same dietary reg- imen based on alfalfa hay and a concentrate feed poor in lipids. Subsequently, the four experimental diets were based on alfalfa hay ad libitum administrated and 800 g/head and day of a concentrate feed con- taining: linseed (L diet) or linseed plus different quantity of CPC to pro- vide 0.4 (L0.4), 0.8 (L0.8) or 1.2 (L1.2) g/kg DM of polyphenols. The trial lasted 5 week, individual milk yield was weekly recorded and analysed for proximate and FA composition. Data were analysed by a repeated measure model. The inclusion of EL and CPC in the diet of dairy ewes did not affect milk yield and proximate composition, however, at the maximum dose, CPC resulted in a significant increase of linoleic and alpha-linolenic acid by 18% and 24%, respectively, if compared to milk fat from ewe fed L diet. At the same time, milk fat from ewe fed L1.2 diet was lower in t11 18:1, CLA content (-38% for both FA) and other intermedi- ates of the biohydrogenation process, probably as a consequence of a perturbing effect of OP on rumen bacteria responsible of the biohydro- genation of dietary PUFA. In conclusion, addition of OP to diet supple- mented with EL enhanced the content of PUFA in milk fat from dairy ewes, without affecting productive performance of the animals

Chestnut or quebracho tannins in the diet of grazing ewes supplemented with soybean oil: Effects on animal performances, blood parameters and fatty acid composition of plasma and milk lipids

The aim of the present study was to evaluate the effect of the inclusion of chestnut or quebracho tannin extracts in the diet of grazing ewes supplemented with soybean oil, on the blood plasma and milk fatty acid profile, milk quality traits and animal metabolic profile. Eighteen Comisana ewes at 172 ± 6 days in milking were allotted into 3 experimental groups. Diets were characterized by pasture ad libitum administered and by 800 g/head and day of 3 experimental concentrates containing 84.5 g of soybean oil/kg of DM and 52.8 g/kg DM of bentonite (Control diet) or 52.8 g/kg DM of chestnut tannin extract (hydrolysable tannins, CHE diet) or 52.8 g/kg DM of quebracho tannin extract (condensed tannins, QUE diet). The trial lasted 4 weeks after 15 days of adaptation to the feeding regimen. Milk yield was daily recorded while milk composition and blood parameters were weekly analysed. CHE and QUE did not affect the milk yield and composition. Casein Index was affected by diet and it was significant higher in milk from animals fed QUE (P < 0.0259). The clotting parameters with the exception of a30were affected by tannins: r was higher for QUE milk while k20increased regardless the kind of tannin. Blood parameters were not affected by tannins and the oxidative status of ewes, determined using MDA as indicator, did not present significant differences among groups, regardless the concentrates fed to animals. Fatty acid profile of blood plasma demonstrated that tannin extract, regardless the source, favored the accumulation of vaccenic acid (trans-11 18:1) reducing the hematic concentration of stearic acid (18:0). Only few significant differences in milk fatty acid profile were found. In particular, rumenic acid (cis-9, trans-11 18:2) increased when the concentrates contained polyphenols and the stronger effect is reached with QUE (P < 0.0002)

Effect of increasing amounts of olive crude phenolic concentrate in the diet of dairy ewes on rumen liquor and milk fatty acid composition

Agro-industrial by-products contain several secondary plant metabolites, such as polyphenols, tannins, saponins, and essential oils. The effects of these compounds on animal metabolism may vary significantly according to the dose, the chemical nature of the molecules, and the overall composition of the diet. In the Mediterranean area, the olive oil extraction is associated with 2 by-products: olive pomace and wastewater, both rich in polyphenols. In particular, wastewater may be further processed to obtain olive crude phenolic concentrate (OCPC). An experiment was carried out aiming to evaluate animal performance, milk fatty acid (FA) profile, diversity of rumen microbial population, and rumen liquor FA profile in dairy ewes fed diets containing extruded linseed (EL) and increasing doses of OCPC. Twenty-eight Comisana ewes in mid lactation were allotted to 4 experimental groups. The experiment lasted 5 wk after 3 wk of adaptation. Diets were characterized by lucerne hay administrated ad libitum and by 800 g/ewe and day of 4 experimental concentrates containing 22% of EL on dry matter and increasing dose of OCPC: 0 (L0), 0.6 (L0.6), 0.8 (L0.8), and 1.2 (L1.2) g of OCPC/kg of dry matter. Milk yield was daily recorded and milk composition was analyzed weekly. At the beginning and at the end of the experiment, samples of rumen liquor were collected to analyze FA profile, changes in rumen microbial population, and dimethylacetal (DMA) composition. The inclusion of OCPC did not affect milk yield and gross composition, whereas milk from L0.8 and L1.2 sheep contained higher concentrations of linoleic (+18%) and α-linolenic acid (+24%) and lower concentration of the rumen biohydrogenation intermediates. A similar pattern was observed for rumen liquor FA composition. No differences were found in the diversity of the rumen microbial population. Total amount of DMA did not differ among treatments, whereas significant differences were found in the concentration of individual DMA; in the diet with a higher amount of OCPC, DMA 13:0, 14:0, 15:0, and 18:0 increased, whereas DMA 16:0 decreased. Probably the presence of polyphenols in the diet induced a rearrangement of bacteria membrane phospholipids as a response to the rumen environment stimulus. Overall, the use of OCPC allowed a significant increase in the polyunsaturated FA content of milk, probably due to a perturbation of the rumen biohydrogenation process. Further studies are needed to understand the correlation between diet composition and the pattern of DMA in rumen liquor

Metformin-Associated Lactic Acidosis Undergoing Renal Replacement Therapy in Intensive Care Units: A Five-Million Population-Based Study in the North-West of Italy

Background: Metformin-associated lactic acidosis (MALA) is a severe complication of drug administration with significant morbidity and mortality. So far no study in large population areas have examined the incidence, clinical profile and outcome of acute kidney injury (AKI)-MALA patients admitted in intensive care units (ICUs) and treated by renal replacement therapy (MALA-RRT). Methods: Retrospective analysis over a 6-year period (2010-2015) in Piedmont and Aosta Valley regions (5,305,940 inhabitants, 141,174 diabetics treated with metformin) of all MALA-RRT cases. Results: One hundred and seventeen cases of AKI-MALA-RRT were observed (12.04/100,000 metformin treated diabetics, 1.45% of all RRT-ICU patients). Survival rate was 78.3%. The average duration of RRT was 4.0 days at mean dialysis effluent of 977 mL/kg/day. At admission most patients were dehydrated, and experienced shock and oliguria. Conclusion: Our data showed that MALA-RRT is a common complication, needing more prevention. Adopted policy of early, extended, continuous and high efficiency dialysis could contribute to an observed high survival rate

Concorso internazionale di progettazione “Il Ponte, il Tunnel, la Storia” - Progetto di un Modello Integrato e Multifunzionale di Museo dell’Autostrada

Il tema del concorso internazionale “Il Ponte, il Tunnel, la Storia” - sezione C "Progetto di rinaturalizzazione e valorizzazione paesaggistica lungo l'Autostrada Salerno-Reggio Calabria, comprensivo di un museo autostradale", indetto dall’ANAS va inserito all’interno del più ampio ambito di ricerca che riguarda tematiche quali infrastrutture complesse, mobilità, ambiente e sostenibilità, che coinvolge alle differenti scale di intervento e con diversi orientamenti disciplinari l’attività di ricerca del Dipartimento BEST. La specificità e allo stesso tempo la complessità dell’oggetto del concorso hanno definito fin da subito la volontà di concretizzare un gruppo di progettazione interdisciplinare, in grado di affrontare le diverse criticità da differenti punti di vista, cercando di ottenere in ogni momento dello sviluppo dell’idea progettuale una verifica delle problematiche multipla e trasversale. All’interno del processo di valorizzazione dei numerosi beni culturali che innervano il panorama italiano, i sistemi infrastrutturali e la loro mirata definizione possono costituire uno strategico strumento di riqualificazione del territorio attraverso l’applicazione di un duplice atteggiamento progettuale mirato all’elaborazione di consolidate metodologie di intervento: da un lato l’incentivazione di un processo di conservazione integrata teso alla valorizzazione delle strutture esistenti che, mediante un atteggiamento conservativo di tipo dinamico, ottimizzi gli spazi e le dotazioni dei manufatti esistenti e non, incorporandoli all’interno di un processo di riqualificazione materiale, funzionale, economica e sociale;dall’altro lato l’attuazione di un processo di sviluppo sostenibile perseguibile mediante la pianificazione, realizzazione e gestione di nodi museali tecnologicamente evoluti, nel tentativo di elaborare un itinerario culturale e ricreativo, diffuso e fruibile lungo la rete autostradale. Obiettivo di tale processo è quello di trasformare l’autostrada in luogo esperienziale che consenta, durante il viaggio, di condividere momenti significativi di socializzazione, avendo l’opportunità di praticare attività di svago e di formazione mediante la partecipazione attiva a un programma di attività culturali diversificate. Il viaggiatore potrà così esperire contemporaneamente a tre differenti modalità di approccio alla sosta: emozionale (sentirsi bene), razionale (avere l’opportunità di conoscere), sensoriale (sentirsi a proprio agio in un ambiente)

Twelve Variants Polygenic Score for Low-Density Lipoprotein Cholesterol Distribution in a Large Cohort of Patients With Clinically Diagnosed Familial Hypercholesterolemia With or Without Causative Mutations

: Background A significant proportion of individuals clinically diagnosed with familial hypercholesterolemia (FH), but without any disease-causing mutation, are likely to have polygenic hypercholesterolemia. We evaluated the distribution of a polygenic risk score, consisting of 12 low-density lipoprotein cholesterol (LDL-C)-raising variants (polygenic LDL-C risk score), in subjects with a clinical diagnosis of FH. Methods and Results Within the Lipid Transport Disorders Italian Genetic Network (LIPIGEN) study, 875 patients who were FH-mutation positive (women, 54.75%; mean age, 42.47±15.00 years) and 644 patients who were FH-mutation negative (women, 54.21%; mean age, 49.73±13.54 years) were evaluated. Patients who were FH-mutation negative had lower mean levels of pretreatment LDL-C than patients who were FH-mutation positive (217.14±55.49 versus 270.52±68.59 mg/dL, P<0.0001). The mean value (±SD) of the polygenic LDL-C risk score was 1.00 (±0.18) in patients who were FH-mutation negative and 0.94 (±0.20) in patients who were FH-mutation positive (P<0.0001). In the receiver operating characteristic analysis, the area under the curve for recognizing subjects characterized by polygenic hypercholesterolemia was 0.59 (95% CI, 0.56-0.62), with sensitivity and specificity being 78% and 36%, respectively, at 0.905 as a cutoff value. Higher mean polygenic LDL-C risk score levels were observed among patients who were FH-mutation negative having pretreatment LDL-C levels in the range of 150 to 350 mg/dL (150-249 mg/dL: 1.01 versus 0.91, P<0.0001; 250-349 mg/dL: 1.02 versus 0.95, P=0.0001). A positive correlation between polygenic LDL-C risk score and pretreatment LDL-C levels was observed among patients with FH independently of the presence of causative mutations. Conclusions This analysis confirms the role of polymorphisms in modulating LDL-C levels, even in patients with genetically confirmed FH. More data are needed to support the use of the polygenic score in routine clinical practice