Background: Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDLcholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality.Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). Methods: We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major candidate genes for monogenic hypercholesterolemia (LDLR, APOB, PCSK9, APOE, LDLRAP1, STAP1). Results: A total of 213 variants were detected in 1076 subjects. About 90% of them had a pathogenic or likely pathogenic variants. More than 94% of patients carried pathogenic variants in LDLR gene, 27 of which were novel. Pathogenic variants in APOB and PCSK9 were exceedingly rare. We found 4 true homozygotes and 5 putative compound heterozygotes for pathogenic variants in LDLR gene, as well as 5 double heterozygotes for LDLR/APOB pathogenic variants. Two patients were homozygous for pathogenic variants in LDLRAP1 gene resulting in autosomal recessive hypercholesterolemia. One patient was found to be heterozygous for the ApoE variant p.(Leu167del), known to confer an FH phenotype. Conclusions: This study shows the molecular characteristics of the FH patients identified in Italy over the last two years. Full phenotypic characterization of these patients and cascade screening of family members is now in progress.

Background and aims: Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network). Methods: Observational, multicenter, retrospective and prospective study involving about 40 Italian clinical centers. Genetic testing of the appropriate candidate genes at one of six molecular diagnostic laboratories serving as nationwide DNA diagnostic centers. Results and conclusions: From 2012 to October 2016, available biochemical and clinical information of 3480 subjects with familial hypercholesterolemia identified according to the Dutch Lipid Clinic Network (DLCN) score were included in the database and genetic analysis was performed in 97.8% of subjects, with a mutation detection rate of 92.0% in patients with DLCN score 6. The establishment of the LIPIGEN network will have important effects on clinical management and it will improve the overall identification and treatment of primary dyslipidemias in Italy.

The development of bone permanent implants with a porous structure favoring their integration with the surrounding tissues is emerging as an attractive field of application of additive manufacturing (AM). This article reports on the investigation of the suitability of a hybrid AM technique, that is, computer‐aided wet‐spinning (CAWS), to fabricate novel poly(methyl methacrylate) (PMMA) constructs as porous implant prototypes. The optimization of the processing parameters to fabricate PMMA samples with a predefined internal porous structure and different external shapes is described. The study demonstrates that tailoring post‐processing conditions represents a powerful tool to optimize samples macroscopic aspect, micromorphology, and mechanical properties. In particular, the possibility of obtaining a dual‐scale porosity through the integration of the macroporous structure determined by the material lay‐down pattern with a submicrometric porosity resulting from the phase inversion process governing polymer solidification, together with the possibility of purifying the employed commercial material from residual monomer during coagulation in ethanol, are reported as noteworthy advantages of CAWS over other AM techniques. A natural progression of this work is the development of relevant complex anatomical prototypes with tailored porosity by processing digital data obtained from computer tomography imaging of bone defects.

Recibido el 26 de octubre 2011 / Aceptado el 13 de mayo 2012 ResúmenLa asociación de estrés y eventos coronarios agudos ha sido extensamente estudiada. En relación a un evento estresante existiría un aumento en la liberación de catecolaminas que incide en un incremento en la presión arterial y alteraciones de hemostasia, como sería el caso de un terremoto. En el presente trabajo se describe la relación contemporánea observada entre el terremoto del 27 de febrero del 2010 y el diagnóstico de lesión subepicárdica, en electrocardiogramas recibidos en ITMS, Telemedicina de Chile. Se analizaron 280.592 electrocardiogramas (ECGs) provenientes de todo el territorio nacional, que corresponden a un periodo de 12 meses de los años 2009 y 2010. Se realizó una comparación estadística entre el porcentaje de lesiones subepicárdicas registradas en el fin de semana del terremoto (27/02/2010 y 28/02/2010) versus los fines de semana de los meses estudiados. Se obtuvieron los datos correspondientes a siete pacientes que se encontraban con monitoreo ambulatorio de presión arterial (MAPA) el día 27/02. El diagnóstico de lesión subepicárdica se hizo en 1.795 trazados, correspondientes a un 0.64% del total de ECGs recibidos. Hubo un aumento estadísticamente significativo de las lesiones subepicárdicas (p<0,05) en el fin de semana del terremoto, la distribución por edad se mantuvo similar al resto de los períodos analizados. Sin embargo se invirtió la distribución por género durante dicho fin de semana siendo mayor en mujeres que en hombres, como es en el resto de los períodos analizados. En los registros MAPA se documentó un aumento de la presión arterial y frecuencia cardíaca en relación al evento estresante. Se confirmó entonces un aumento estadísticamente significativo del diagnóstico electrocardiográfico de lesiones subepicárdicas en relación al estrés producido por el terremoto del 27 de febrero de 2010.

No abstract