Measurements of charm rare decays at LHCb

Following the intriguing hints of deviations from the Standard Model in rare B meson decays, searches for rare and forbidden decays of charm hadrons become a hot topic again. We present recent results on Flavour Changing Neutral Current $D^{0}\rightarrow\mu^+ \mu^-$, $D^0 \rightarrow\mu^+\mu^- \pi^+ \pi^-$, $D^{\pm}_{(s)}\rightarrow \pi^{\pm} \mu^+\mu^-$ and LFV $D^{\pm}_{(s)}\rightarrow \pi^{\mp}\mu^{\pm}\mu^{\pm}$ obtained at LHCb.Comment: To be published in the proceedings of CHARM-2015, Detroit, MI, 18-22 May 201

Apoyo psicosocial al instituto nacional penitenciario y carcelario INPEC

TablasMostraremos los resultados obtenidos en la realización de la práctica como experiencia profesional dirigida en el EPC YOPAL INPEC, lo cual representa este documento final, se realizaron diferentes actividades relacionadas con el área de psicología social comunitaria y el área de reinserción social, el trabajo se realizó en con la parte interna del establecimiento es decir en su mayoría fue dirigida a esta población de internos o reclusos del establecimiento, pues también estuvo proyectada una intervención con funcionarios. Se dio curso y desarrollo a programas de orden de la subdirección nacional para el área de reinserción. Aprovechamos para mencionar y dar relevancia a las manifestaciones que se dieron a través de los informes la falta del recurso y talento humano para estos, lo que se hizo como primera medida fue apoyar esta área, darle prioridad a lo solicitado, sortear las necesidades y hacer creativamente que el tiempo alcanzara para conseguir los objetivos planteados dentro de la propuesta como profesional de apoyo, la cual iba encaminada en la prestación del servicio de actividades al orden psicosocial para el establecimiento como se requiriera de acuerdo a lo estipulado dentro del marco del convenio interinsticional. 7 Se prestó colaboración para cubrir otros espacios y solicitudes de la misma área de psicología; funciones que fueron de gran ayuda y crecimiento profesional, las cuales no estaban incluidas en la propuesta pero que en su momento se necesitó de la ayuda,; estas actividades extra fueron de gran crecimiento profesional y personal. Se ejecutaron actividades valiosas y fructíferas donde hubo gran participación de la comunidad carcelaria, se brindaron los espacios, las herramientas de ayuda para la realización de cada una de las actividades y lo más importante la población siempre estuvo en disposición y demostraron interés por los procesos de resocialización, se mostraban agradecidos con estos acompañamientos psicosociales brindados. El desarrollo de las demás actividades estuvieron de igual forma supervisadas y aprobadas por el comando de vigilancia y demás áreas encargadas de la seguridad del establecimiento, diariamente había que subir los informes o reportes al sistema nacional de lo que se realizaba se cuenta con las respectivas evidencias como lo son fotografías, ejercicios de desarrollo, planillas de asistencia etc.In carrying out the practice as professional experience in the EPC YOPAL directed INPEC, which represents the final document, there were different activities related to the area of community social psychology and social reintegration area, work was done on the part ie internal establishment was mostly directed at this population of inmates or inmates of the establishment, was also projected as an intervention with officials. action was taken and development programs by the sub national reintegration area and it has been shown in the reports lack of human resource and talent for these, what was done as a first step was to support this area, giving priority to As requested, negotiate and make creative needs that time to get reach the objectives within the proposed professional support, which was aimed at the service of the order psychosocial activities for the establishment as required according to stipulated within the framework of the agreement interinsticional. Support was provided to cover other areas and applications of the same area of psychology; functions were extremely helpful and professional growth, which were not included in the proposal, but that once they 9 need the help, and these extra activities were high professional and personal growth. Were implemented valuable and fruitful activities where there was great participation of the prison community, spaces were provided, support tools for performing each of the activities and most importantly the population was always available and showed interest in processes resocialization, they were grateful to these psychosocial accompaniments provided .. The development of other activities were similarly supervised and approved by the command of surveillance and other areas in charge of the security establishment had to climb daily reports or reports to the national system of what took place is the relevant evidence has such as photographs, development exercises, attendance sheets etc

Uso del Registro de Solicitudes de Medicamentos no Incluidos en el Listado de Medicamentos Esenciales como Nueva Fuente de Información en los Sistemas Nacionales de Farmacovigilancia

AbstractObjectiveTo describe the frequency of adverse drugs events (ADEs) as possible causes of request of drugs not included in national essential Medicines list in Colombia.MethodsThis was a descriptive study developed in a private medical insurance company in Bogota, Colombia. Data were obtained from drug request form of drugs not included in a national essential Medicines list. We analyzed the content of the notes to identify the records related to the occurrence of ADEs in the period 2008 to 2009. Information concerning the adverse event and the drug involved was recorded in a data collection instrument developed by the researchers. The pharmacological classification of drugs was performed according to the Anatomical Therapeutic Chemical Classification System (ATC).ResultsWe study 3,336 request forms of drugs not included in a national essential Medicines list. The level 1 groups of the ATC of drugs with greater frequency of ADEs were the cardiovascular agents (47%), nervous system agents (24%) and antineoplastic and immunomodulating agents (15%). The great majority was cases of light severity (62.7%) and classified as possible (48.4%).ConclusionThe results of this study support the innovative approach of using request form of drug not included in national essential Medicines list to obtain information regarding ADEs in developing countries; recognizing the importance of looking for new sources of report of adverse reactions to diminish the under-notification of ADEs

Circulating MicroRNAs in Elderly Type 2 Diabetic Patients

The circulating microRNAs (miRNAs) associated with type 2 diabetes (T2D) in elderly patients are still being defined. To identify novel miRNA biomarker candidates for monitoring responses to sitagliptin in such patients, we prospectively studied 40 T2D patients (age > 65) with HbA1c levels of 7.5–9.0% on metformin. After collection of baseline blood samples (t0), the dipeptidyl peptidase-IV (DPP-IV) inhibitor (DPP-IVi) sitagliptin was added to the metformin regimen, and patients were followed for 15 months. Patients with HbA1c0.5% after 3 and 15 months of therapy were classified as “responders” (group R, n = 34); all others were classified as “nonresponders” (group NR, n = 6). Circulating miRNA profiling was performed on plasma collected in each group before and after 15 months of therapy (t0 and t15). Intra- and intergroup comparison of miRNA profiles pinpointed three miRNAs that correlated with responses to sitagliptin: miR-378, which is a candidate biomarker of resistance to this DPP-IVi, and miR-126-3p and miR-223, which are associated with positive responses to the drug. The translational implications are as immediate as evident, with the possibility to develop noninvasive diagnostic tools to predict drug response and development of chronic complications

Uso de medicamentos inmunosupresores en pacientes con trasplante renal, hepático y de médula ósea, en una clínica de nivel iii de bogotá

Antecedentes. El trasplante de órganos en la actualidad es una opción terapéutica para los pacientes que cursan estadíos terminales de ciertas patologías; el uso de inmunosupresores contribuye en gran medida a la efectividad de este tipo de tratamientos, ya que es fundamental para evitar el rechazo. El no seguimiento del consumo de medicamentos nuevos, como es el caso de los inmunosupresores que suelen tener precios relativamente elevados, junto con la ampliación injustificada de indicaciones, puede ocasionar un aumento de los costos de la terapia farmacológica y, lo más importante, causar riesgos en el paciente trasplantado. Objetivos. Describir y caracterizar el uso de medicamentos inmunosupresores en pacientes con trasplante renal, de médula ósea alogénico y hepático. Material y métodos. Estudio observacional-descriptivo de corte transversal con recolección retrospectiva de la información a un año. Se trata de un estudio de utilización de medicamentos sobre hábitos de prescripción. Resultados. El desenlace global de la terapia del trasplante produce resultados satisfactorios en un 92,5 por ciento (49 pacientes), 5,7 por ciento (3 pacientes) presentan rechazo con retiro del injerto, mientras que un paciente fallece después de ser sometido al trasplante. El medicamento más prescrito es el micofenolato de mofetil, con 41 prescripciones (28%), mientras que el más consumido es la prednisona con 2,38 dosis diaria definidas /100 pacientes/día. Conclusiones. Se evidencia la presencia de micofenolato, ciclosporina y corticoides en la mayoría de los esquemas con algunas prescripciones de anticuerpos monoclonales y globulina antitimocítica

Hepatic microRNA Expression by PGC-1α and PGC-1β in the Mouse.

The fine-tuning of liver metabolism is essential to maintain the whole-body homeostasis and to prevent the onset of diseases. The peroxisome proliferator-activated receptor-γ coactivators (PGC-1s) are transcriptional key players of liver metabolism, able to regulate mitochondrial function, gluconeogenesis and lipid metabolism. Their activity is accurately modulated by post-translational modifications. Here, we showed that specific PGC-1s expression can lead to the upregulation of different microRNAs widely implicated in liver physiology and diseases development and progression, thus offering a new layer of complexity in the control of hepatic metabolism

The effects of chronic lifelong activation of the AHR pathway by industrial chemical pollutants on female human reproduction

Environmental chemicals, such as heavy metals, affect female reproductive function. A biological sensor of the signals of many toxic chemical compounds seems to be the aryl hydrocarbon receptor (AHR). Previous studies demonstrated the environmental of heavy metals in Taranto city (Italy), an area that has been influenced by anthropogenic factors such as industrial activities and waste treatments since 1986. However, the impact of these elements on female fertility in this geographic area has never been analyzed. Thus, in the present study, we evaluated the AHR pathway, sex steroid receptor pattern and apoptotic process in granulosa cells (GCs) retrieved from 30 women, born and living in Taranto, and 30 women who are living in non-contaminated areas (control group), who were undergoing in vitro fertilization (IVF) protocol. In follicular fluids (FFs) of both groups the toxic and essential heavy metals, such as chromiun (Cr), Manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), cadmium (Cd) and lead (Pb), were also analyzed. Higher levels of Cr, Fe, Zn and Pb were found in the FFs of the women from Taranto as compared to the control group, as were the levels of AHR and AHR-dependent cytochrome P450 1A1 and 1B1; while CYP19A1 expression was decreased. The anti-apoptotic process found in the GCs of women fromTaranto was associated with the highest levels of progesterone receptor membrane component 1(PGRMC1), a novel progesterone receptor, the expression of which is subjected to AHR activated by its highest affinity ligands (e.g., dioxins) or indirectly by other environmental pollutants, such as heavy metals. In conclusion, decreased production of estradiol and decreased number of retrieved mature oocytes found in women from Taranto could be due to chronic exposure to heavy metals, in particular to Cr and Pb

Identification and monitoring of Copy Number Variants (CNV) in monoclonal gammopathy

Monoclonal gammopathy of undetermined significance (MGUS) represents the pre-clinical stage of Multiple Myeloma (MM) with the 5% of MGUS progresses to MM. Although the progression from MGUS to MM has not been completely characterized, it is possible to monitor the DNA modifications of patients diagnosed with MGUS to detect early specific genomic abnormalities, including copy number variations (CNV). The CNVs of chromosome 1q and chromosome 13q are associated with a worse prognosis in MM.In the present study, we showed that it is possible to monitor the 1q21 gain and 13q deletion frequencies in gDNA using digital PCR. The CNV analysis of three cell lines with a well-characterized cytogenetic profile were compared with measures performed by a real-time PCR approach and with a digital PCR approach. Then, we analyzed CNVs in CD138+ plasma cells isolated from bone marrow of MGUS and MM patients.Our results show that digital PCR and targeted DNA monitoring represent a specific and accurate technique for the early detection of specific genomic abnormalities both in MM and in MGUS patients.Our results could represent a remarkable advancement in MM and MGUS diagnosis and in CNV analysis for the evaluation of the risk of progression from MGUS to MM

Accumulation and aberrant composition of cholesteryl esters in Scrapie-infected N2a cells and C57BL/6 mouse brains

<p>Abstract</p> <p>Objective</p> <p>Cholesterol changes have been described in prion-cell models and in experimental rodent scrapie; yet, the pattern of this association is still controversial.</p> <p>Methods</p> <p>To shed light on the matter, we analysed and compared cholesterol variations in ScN2a cells and in brains of Scrapie-infected C57Bl/6 mice, using two different methods: a fluorimetric-enzymatic cholesterol assay, and high performance liquid chromatography-mass spectroscopy (HPLC-MS).</p> <p>Results</p> <p>Compared to uninfected controls, similar cholesterol metabolism anomalies were observed in infected cells and brains by both methods; however, only HPLC-MS revealed statistically significant cholesterol variations, particularly in the cholesteryl esters (CE) fraction. HPLC-MS analyses also revealed different fatty acid composition of the CE fraction in cells and brains. In N2a cells, their profile reflected that of serum, while in normal brains cholesteryl-linoleate only was found at detectable levels. Following prion infection, most CE species were increased in the CE pool of ScN2a cells, whereas a conspicuous amount of cholesteryl-arachidonate only was found to contribute to the cerebral increase of CE. Of interest, oral pravastatin administration to Scrapie-infected mice, was associated with a significant reduction of cerebral free cholesterol (FC) along with a concomitant further increase of the CE pool, which included increased amounts of both cholesteryl-linoleate and cholesteryl-arachidonate.</p> <p>Conclusion</p> <p>Although mechanistic studies are needed to establish the pathophysiological relevance of changes in cerebral CE concentrations, to the best of our knowledge this is the first report to provide evidence of increased cholesterol esterification in brains of prion-infected mice, untreated and treated with pravastatin.</p

IDO Mediates TLR9-Driven Protection from Experimental Autoimmune Diabetes

Abstract Originally predicated on the recognition of an increasing prevalence of allergy, the hygiene hypothesis was later found to accommodate the contrasting epidemiologic trends in developed countries for infectious vs autoimmune diseases. Experimentally, reduced exposure to infections will increase the risk of disease in several models of experimental autoimmunity. Although TLRs were initially considered as stimulatory molecules capable of activating early defense mechanisms against invading pathogens, emerging data suggest that they can also exert a regulatory function. In the present study, we evaluated whether TLR3 and TLR9, recognizing microbial dsDNA and CpG-containing DNA sequences, respectively, play a role in the protection from experimental autoimmune diabetes induced in C57BL/6 mice by streptozotocin. In wild-type animals, the disease was accompanied by up-regulation of IDO in pancreatic lymph nodes and would be greatly exacerbated by in vivo administration of an IDO inhibitor. Conversely, administration of a CpG-containing oligodeoxynucleotide greatly attenuated the disease in an IDO-dependent fashion. TLR9-, but not TLR3-deficient mice developed a more robust disease, an event accompanied by lack of IDO induction in pancreatic lymph nodes. Thus, our data suggest that the TLR9-IDO axis may represent a valuable target in the prevention/therapy of type 1 diabetes