Efficacy and safety of niacin/laropiprant therapy in familial hypercholesterolemic patients with coronary artery disease

Background: Cardiovascular disease is the principal cause of premature mortality and morbidity in Europe. Patients with familial hypercholesterolemia are at particularly increased risk and, despite lipid-lowering therapy, continue to experience cardiovascular events. Currently, for these patients a new treatment option is represented by extended-release niacin/laropiprant (ERN/LRPN). Material and Methods: We followed-up for 16 weeks a group of 23 familial hypercholesterolemic patients (mean age 61?7 years, 74% male) with chronic coronary artery disease and ERN/LRPN added on top of maximally tolerated lipid-lowering therapy. ERN/LRPN was administered at the dose of 1 gr/day for the first 4 weeks and then at 2 gr/day for the remaining period. Clinical examination and blood sampling (including lipid profile, renal and hepatic function) were performed at baseline, after 4 weeks, at the end of follow-up, and in the case of eventual clinical manifestations. Results: During follow-up, 14 patients discontinued therapy due to side effects (headache, asthenia, and gastrointestinal disorders in 4 patients, muscle aches and CK increase in 3 patients, eruptive skin rash in 2 patients, onset of diabetes mellitus in 2 patients, dizziness associated with inability to drive in 1 patient, acute hepatitis in 1 patient and palpitations in 1 patient) and 2 patients voluntarily interrupted the therapy. In the remaining 7 patients, an improvement in lipid profile was observed (total cholesterol -14%, HDL cholesterol +7%, LDL cholesterol -16%, Triglycerides -53%, Apolipoprotein A1 +8%, Apolipoprotein B -21%, Apolipoprotein E -31%) in the absence of substantial changes in other laboratory analyses (with the exception of a non-significant increase in uric acid). Intolerable skin flushing was not observed in any patient. In addition, among patients who did report flushing, a reduction in the incidence of the episodes was observed after the first month of therapy

Planeamiento estratégico de la Provincia de Castrovirreyna

El Plan Estratégico de la provincia de Castrovirreyna se realizó con base en el Modelo Secuencial del Proceso Estratégico, el cual desarrolló el Dr. Fernando D’Alessio Ipinza, quien partió de un análisis de la situación actual, para llegar a una situación futura deseada, por medio del establecimiento de la visión, misión, valores, objetivos de largo plazo, corto plazo y estrategias asociadas al entorno y sus fortalezas, debilidades, oportunidades y amenazas. Castrovirreyna es una provincia que se conforma de 13 distritos, es predominantemente rural y tiene un alto grado de pobreza y pobreza extrema, posee abundantes recursos que podrían permitirle mejorar su posición, debido a que no tiene la promoción e inversión necesaria para capitalizar la riqueza de su patrimonio en actividades productivas que le permitan desarrollarse y crecer. La propuesta del Plan se basa en el desarrollo de la infraestructura (vial y de comunicaciones) y de los servicios básicos (salud, educación e internet) que sirva de soporte e incremente el nivel de vida y la competitividad de la provincia; el desarrollo de sectores económicos como agropecuario, acuícola y turismo, a través de la mejora de la tecnología de producción de especies propias de la provincia y los beneficios tributarios, otorgados desde el Estado y las capacitaciones e incentivos a la generación de clústeres, también la participación de la población en todos los procesos de la búsqueda del desarrollo provincial. Asimismo, se orienta a motivar a las nuevas generaciones al emprendimiento teniendo en cuenta las potencialidades de la provincia, y de esta manera poder reducir las brechas de pobreza y desigualdad existentesThe Strategic Plan of the province of Castrovirreyna has been made based on the sequential model of the Strategic Process developed by Dr. Fernando D’Alessio Ipinza, based on an analysis of the current situation, to reach a desired future situation, through the establishment of vision, mission, values, long-term goals, short-term and related to the environment and their strategies strengths, weaknesses, opportunities and threats. Castrovirreyna is a province that is composed of 13 districts, it’s predominantly rural and has a high degree of poverty and extreme poverty, it has abundant resources that could enable it to improve its position because it does not have the promotion and investment needed to capitalize on the wealth of its assets in activities productive that allow develop and grow. Plan’s proposal is based on the development of the infrastructure (roads and communications) and of the basic services (health, education and internet) to serve as a support and increase the standard of living and competitiveness of the province; the development of economic sectors such as agriculture, aquaculture and tourism through improved production technology of species native of the province and the tax benefits granted from the State and trainings and incentives to generate clusters, also participation of the population in all processes of the search for provincial development. Additional aims to encourage new generations to entrepreneurship taking into account the potential of the province, and thus to reduce the gaps existing poverty and inequalityTesi

Molecular Mechanisms Generating and Stabilizing Terminal 22q13 Deletions in 44 Subjects with Phelan/McDermid Syndrome

In this study, we used deletions at 22q13, which represent a substantial source of human pathology (Phelan/McDermid syndrome), as a model for investigating the molecular mechanisms of terminal deletions that are currently poorly understood. We characterized at the molecular level the genomic rearrangement in 44 unrelated patients with 22q13 monosomy resulting from simple terminal deletions (72%), ring chromosomes (14%), and unbalanced translocations (7%). We also discovered interstitial deletions between 17–74 kb in 9% of the patients. Haploinsufficiency of the SHANK3 gene, confirmed in all rearrangements, is very likely the cause of the major neurological features associated with PMS. SHANK3 mutations can also result in language and/or social interaction disabilities. We determined the breakpoint junctions in 29 cases, providing a realistic snapshot of the variety of mechanisms driving non-recurrent deletion and repair at chromosome ends. De novo telomere synthesis and telomere capture are used to repair terminal deletions; non-homologous end-joining or microhomology-mediated break-induced replication is probably involved in ring 22 formation and translocations; non-homologous end-joining and fork stalling and template switching prevail in cases with interstitial 22q13.3. For the first time, we also demonstrated that distinct stabilizing events of the same terminal deletion can occur in different early embryonic cells, proving that terminal deletions can be repaired by multistep healing events and supporting the recent hypothesis that rare pathogenic germline rearrangements may have mitotic origin. Finally, the progressive clinical deterioration observed throughout the longitudinal medical history of three subjects over forty years supports the hypothesis of a role for SHANK3 haploinsufficiency in neurological deterioration, in addition to its involvement in the neurobehavioral phenotype of PMS

Clinical and socio-demographic determinants of self-care maintenance, monitoring and management in us adults with type 2 diabetes mellitus

The aims of this study were to describe self-care in US T2DM patients and to identify clinical and sociodemographic determinants of self-care maintenance, monitoring, and management in US T2DM patients. A secondary analysis was performed using data from a cross-sectional study done to test the psychometric performance of the Self-Care of Diabetes Inventory in US English speaking adults with diabetes. In our sample (n = 207), self-care maintenance was adequately performed (median = 75), self-care monitoring was borderline (median = 67.6) and self-care management was poor (median = 55.6). Low income (p = .0019) and low self-care confidence (p < .0001) were associated with relatively lower self-care maintenance. Not taking insulin (p = .0153) and low self-care confidence (p < .0001) were associated with relatively low self-care monitoring. Low self-care confidence (p < .0001) was associated with low self-care management. Self-care confidence is a strong determinant of self-care. Interventions designed to improve self-care confidence are urgently needed

COX-2 is induced by HGF stimulation in Met-positive thyroid papillary carcinoma cells and is involved in tumour invasiveness

Thyroid papillary carcinoma (TPC) cells express high levels of cytoplasmic cyclo-oxygenase 2 protein. Analysis of microdissected samples of the tumour and of the paired normal thyroid tissue confirmed that mRNA transcripts for cyclo-oxygenase 2 (COX-2) were significantly more numerous in the tumour (7.6 +/- 13-fold; p = 0.01). High levels of COX-2 mRNA were not associated with age, sex, tumour size or lymph node metastasis. COX-2 was not homogeneously expressed throughout the tumour, but was significantly higher at the tumour invasion front. Hepatocyte growth factor (HGF) can up-regulate (he expression of COX-2 mRNA. A marked increase in COX-2 mRNA levels was observed in 8/8 primary TPC cultures after HGF stimulation (6.3 +/- 6-fold) and in two papillary carcinoma cell lines (TPC-1 and NPA). Specific involvement of the high-affinity HGF receptor (Met protein) was suggested by the observation that PHA-665752, an inhibitor of the catalytic activity of c-Met kinase, caused a 54% reduction of the hepatocyte growth factor-induced COX-2 up-regulation. The possibility that HGF-Met interactions also had a causative role in the up-regulation of COX-2 in vivo was investigated in 30 tumour samples, where it was found that there was a statistically significant correlation (p = 0.001, r = 0.85) in the levels of expression of MET and COX-2 RNAs. The biological role of COX-2 in TPC cells was investigated by treating the TPC cell lines with the specific COX-2 inhibitor NS-398. It was found that NS-398 treatment significantly reduced the migration (50-75%) and invasiveness (47-92%) of tumour cells, but did not alter cell proliferation. Our data suggest that the increased expression of Met protein in TPC cells has a role in up-regulating the expression of COX-2, which in turn contributes to the invasive capacity of TPC cells. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by, John Wiley & Sons, Ltd

Persistent complex bereavement disorder in caregivers of terminally ill patients undergoing supportive-expressive treatment. A pilot study

BACKGROUND: The proposal of persistent complex bereavement disorder (PCBD) in the DSM-V increased the interest on the impact of grief on the psychological health. AIMS: Investigating the time course of psychological symptoms, emotional and social abilities in caregivers (undergoing or not to supportive-expressive treatment) of terminally ill cancer patients from 1 months before loss to 14 months after it. METHOD: Thirty-three of 60 caregivers were assessed by PG-12, HAM-A, HAM-D, TAS-20 and ASQ, at the admission in Hospice, and after 3, 10 and 14 months from the loss. Twelve caregivers adhered to follow a supportive-expressive treatment and 21 caregivers did not. RESULTS: PG-12, anxiety, and depression scores decreased in both groups over time. The score of difficulty in identifying emotions and confidence with closeness decreased significantly only in the treated-group. PG-12 score at T0 was able to predict the DSM V diagnosis of PCBD at T3. CONCLUSIONS: Findings showed a decrease of the anxiety, depression, security in the attachment style and an increase of the ability to identify emotions during the first year after loss in caregivers of terminally ill cancer patients. Pre-loss assessment of prolonged grief risk seems useful to predict the diagnosis of PCBD 1 year after los

Self-care in People with Type 2 Diabetes Mellitus – Research Protocol of a Multicenter Mixed Methods Study (SCUDO)

About 11% of the adult global populations is estimated to be living with type 2 diabetes mellitus (T2DM) by 2040. T2DM requires people to make decisions regarding complex therapeutic regimes, to maintain their well-being and quality of life, to manage symptoms and to reduce disease complications. All these behaviours, requiring knowledge, motivation, experience, and skills, have been referred to the concept of self-care. The intricacy and multidimensionality of T2DM self-care requires a complex approach to its overall comprehension. This Embedded Mixed Method study aims to investigate the experience of self-care in Type 2 Diabetes Mellitus adult patients. It comprises a prospective observational design, and an interpretive description. Quantitative data will be collected with validated questionnaires from 300 patients at baseline and once a year for two years on: diabetes self-care, quality of life, diabetes related distress, and sleep quality. Socio-demographic and clinical data will be collected from medical records. Qualitative data will be collected using semi-structured interviews on circa 10-20 patients, at baseline and once a year for two years, analysed according to interpretive description. Quantitative and qualitative data will be analysed separately and then merged and interpreted. This study will expand our understanding of self-care in people with T2DM. The expected outcome will be a better understanding of the effect of self-care on glycaemic control and therefore clinical outcomes and costs.Key words: Type 2 Diabetes Mellitus, Self-care, Mixed Method Research, Research Protocol, Self-management, Self-care of Diabetes Inventory  Self-care nelle persone con diabete mellito di tipo 2 - Protocollo di ricerca di uno studio multicentrico con metodo mistoSi stima che entro il 2040 circa l'11% della popolazione mondiale sarí  affetta da diabete mellito di tipo 2 (T2DM). Il T2DM richiede che le persone che ne sono affette prendano decisioni rispetto a complessi regimi terapeutici, per mantenere il loro benessere e qualití  di vita, per gestire sintomi e ridurre le complicanze legate alla malattia. Tutti questi comportamenti che richiedono conoscenze, motivazione, esperienza e abilití , vengono identificate col concetto di self-care. La complessití  e la multidimensionalití  del self-care richiedono un approccio adeguato alla loro comprensione. Questo studio mixed method ha lo scopo di esplorare l'esperienza del self-care nelle persone affette da diabete mellito di tipo 2. Comprende uno studio osservazionale longitudinale e una interpretive description. I dati quantitativi verranno raccolti attraverso la somministrazione a 300 persone, all'inizio dello studio e poi una volta all'anno per due anni, di questionari validati circa: il self-care nel diabete, la qualití  di vita, il distress legato al diabete, la qualití  del sonno. Dati socio-demografici e clinici verranno raccolti attraverso la consultazione delle cartelle cliniche. I dati qualitativi, raccolti attraverso interviste semi-strutturate con circa 10-20 pazienti, all'inizio dello studio e poi una volta all'anno per due anni, verranno analizzati secondo l'interpretive description. I dati quantitativi e qualitativi verranno analizzati separatamente, dopodiché uniti ed interpretati. Questo studio vuole aumentare la nostra comprensione del self-care nelle persone con T2DM. L'outcome atteso sarí  una migliore comprensione del self-care e dell'effetto del self-care sul controllo glicemico e quindi sugli outcome clinici ed i costi.Parole Chiave: Diabete mellito di tipo 2, Self-care, metodi misti, protocollo di ricerca, Self-management, Self-care of Diabetes Inventor