Investigating REPAIRv2 as a Tool to Edit CFTR mRNA with Premature Stop Codons

Cystic fibrosis (CF) is caused by mutations in the gene encoding the transmembrane conductance regulator (CFTR) protein. Some CF patients are compound heterozygous or homozygous for nonsense mutations in the CFTR gene. This implies the presence in the transcript of premature termination codons (PTCs) responsible for a truncated CFTR protein and a more severe form of the disease. Aminoglycoside and PTC124 derivatives have been used for the read-through of PTCs to restore the full-length CFTR protein. However, in a precision medicine framework, the CRISPR/dCas13b-based molecular tool “REPAIRv2” (RNA Editing for Programmable A to I Replacement, version 2) could be a good alternative to restore the full-length CFTR protein. This RNA editing approach is based on the targeting of the deaminase domain of the hADAR2 enzyme fused to the dCas13b protein to a specific adenosine to be edited to inosine in the mutant mRNA. Targeting specificity is allowed by a guide RNA (gRNA) complementarily to the target region and recognized by the dCas13b protein. Here, we used the REPAIRv2 platform to edit the UGA PTC to UGG in dierent cell types, namely IB3-1 cells, HeLa, and FRT cells engineered to express H2BGFPopal and CFTRW1282X, respectively

Parallel or intersecting lines? Intelligent bibliometrics for investigating the involvement of data science in policy analysis

Efforts to involve data science in policy analysis can be traced back decades but transforming analytic findings into decisions is still far from straightforward task. Data-driven decision-making requires understanding approaches, practices, and research results from many disciplines, which makes it interesting to investigate whether data science and policy analysis are moving in parallel or whether their pathways have intersected. Our investigation, from a bibliometric perspective, is driven by a comprehensive set of research questions, and we have designed an intelligent bibliometric framework that includes a series of traditional bibliometric approaches and a novel method of charting the evolutionary pathways of scientific innovation, which is used to identify predecessor–descendant relationships in technological topics. Our investigation reveals that data science and policy analysis have intersecting lines, and it can foresee that a cross-disciplinary direction in which policy analysis interacting with data science has become an emergent area in both communities. However, equipped with advanced data analytic techniques, data scientists are moving faster and further than policy analysts. The empirical insights derived from our research should be beneficial to academic researchers and journal editors in related research communities, as well as policy-makers in research institutions and funding agencies

Analysis of the gastrin-releasing peptide receptor gene in Italian patients with autism spectrum disorders

The gastrin-releasing peptide receptor (GRPR) was implicated for the first time in the pathogenesis of Autism spectrum disorders (ASD) by Ishikawa-Brush et al. [Ishikawa-Brush et al. (1997): Hum Mol Genet 6: 1241-1250]. Since this original observation, only one association study [Marui et al. (2004): Brain Dev 26: 5-7] has further investigated, though unsuccessfully, the involvement of the GRPR gene in ASD. With the aim of contributing further information to this topic we have sequenced the entire coding region and the intron/exon junctions of the GRPR gene in 149 Italian autistic patients. The results of this study led to the identification of four novel point mutations, two of which, that is, C6S and L181F, involve amino acid changes identified in two patients with ASD and Rett syndrome, respectively. Both the leucine at position 181 and the cysteine at position 6 are strongly conserved in vertebrates. C6S and L181F mutant proteins were expressed in COS-7 and BALB/3T3 cells, but they did not affect either GRP's binding affinity or its potency for stimulating phospholipase C-mediated production of inositol 1,4,5-trisphosphate. In summary, our results do not provide support for a major role of the GRPR gene in ASD in the population of patients we have studied. However, there is a potential role of C6S and L181F mutations on GRPR function, and possibly in the pathogenesis of the autistic disorders in the two patient

Treatment of peripheral arterial disease in diabetes: a consensus of the Italian Societies of Diabetes (SID, AMD), Radiology (SIRM) and Vascular Endovascular Surgery (SICVE).

AbstractDiabetic foot (DF) is a chronic and highly disabling complication of diabetes. The prevalence of peripheral arterial disease (PAD) is high in diabetic patients and, associated or not with peripheral neuropathy (PN), can be found in 50% of cases of DF. It is worth pointing out that the number of major amputations in diabetic patients is still very high. Many PAD diabetic patients are not revascularised due to lack of technical expertise or, even worse, negative beliefs because of poor experience. This despite the progress obtained in the techniques of distal revascularisation that nowadays allow to reopen distal arteries of the leg and foot. Italy has one of the lowest prevalence rates of major amputations in Europe, and has a long tradition in the field of limb salvage by means of an aggressive approach in debridement, antibiotic therapy and distal revascularisation. Therefore, we believe it is appropriate to produce a consensus document concerning the treatment of PAD and limb salvage in diabetic patients, based on the Italian experience in this field, to share with the scientific community

Impact of vaccination against Haemophilus influenzae type b with and without a booster dose on meningitis in four South American countries

Fil: García, Salvador. Pan American Health Organization, Washington DC; Estados Unidos.Fil: Lagos, Rosanna. Centro para Vacunas en Desarrollo (CVD-Chile), Santiago; Chile.Fil: Muñoz, Alma. Centro para Vacunas en Desarrollo (CVD-Chile), Santiago; Chile.Fil: Picón, Teresa. National Immunization Program and Department of Epidemiologic Surveillance, Ministry of Health, Montevideo; Uruguay.Fil: Rosa, Raquel. National Immunization Program and Department of Epidemiologic Surveillance, Ministry of Health, Montevideo; Uruguay.Fil: Alfonso, Adriana. National Immunization Program and Department of Epidemiologic Surveillance, Ministry of Health, Montevideo; Uruguay.Fil: Abriata, Graciela. Instituto Nacional del Cáncer, Ministerio de Salud de la Nación, Buenos Aires; Argentina.Fil: Gentile, Angela. Hospital de Niños Ricardo Gutierrez, Epidemiología, Buenos Aires; Argentina.Fil: Romanin, Viviana. Hospital de Niños Ricardo Gutierrez, Epidemiología, Buenos Aires; Argentina.Fil: Regueira, Mabel. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Chiavetta, Laura. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Agudelo, Clara Inés. Instituto Nacional de Salud, Bogotá; Colombia.Fil: Castañeda, Elizabeth. Instituto Nacional de Salud, Bogotá; Colombia.Fil: De la Hoz, Fernando. Facultad de Medicina, Departamento de Salud Pública, Universidad Nacional de Colombia, Bogotá; Colombia.Fil: Higuera, Ana Betty. Secretaria de Salud de Bogotá, Bogotá; Colombia.Fil: Arce, Patricia. Secretaria de Salud de Bogotá, Bogotá; Colombia.Fil: Cohen, Adam L.. National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA; Estados Unidos.Fil: Verani, Jennifer. National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA; Estados Unidos.Fil: Zuber, Patrick. Department of Immunization, Vaccines and Biologicals, World Health Organization, Geneva; Suiza.Fil: Gabastou, Jean-Marc. Pan American Health Organization, Washington DC; Estados Unidos.Fil: Pastor, Desiree. Pan American Health Organization, Washington DC; Estados Unidos.Fil: Flannery, Brendan. Pan American Health Organization, Washington DC; Estados Unidos.Fil: Andrus, Jon. Pan American Health Organization, Washington DC; Estados Unidos.To inform World Health Organization recommendations regarding use of Haemophilus influenzae type b (Hib) vaccines in national immunization programs, a multi-country evaluation of trends in Hib meningitis incidence and prevalence of nasopharyngeal Hib carriage was conducted in four South American countries using either a primary, three-dose immunization schedule without a booster dose or with a booster dose in the second year of life. Surveillance data suggest that high coverage of Hib conjugate vaccine sustained low incidence of Hib meningitis and low prevalence of Hib carriage whether or not a booster dose was used

Impact of vaccination against Haemophilus influenzae type b with and without a booster dose on meningitis in four South American countries

Fil: García, Salvador. Pan American Health Organization, Washington DC; Estados Unidos.Fil: Lagos, Rosanna. Centro para Vacunas en Desarrollo (CVD-Chile), Santiago; Chile.Fil: Muñoz, Alma. Centro para Vacunas en Desarrollo (CVD-Chile), Santiago; Chile.Fil: Picón, Teresa. National Immunization Program and Department of Epidemiologic Surveillance, Ministry of Health, Montevideo; Uruguay.Fil: Rosa, Raquel. National Immunization Program and Department of Epidemiologic Surveillance, Ministry of Health, Montevideo; Uruguay.Fil: Alfonso, Adriana. National Immunization Program and Department of Epidemiologic Surveillance, Ministry of Health, Montevideo; Uruguay.Fil: Abriata, Graciela. Instituto Nacional del Cáncer, Ministerio de Salud de la Nación, Buenos Aires; Argentina.Fil: Gentile, Angela. Hospital de Niños Ricardo Gutierrez, Epidemiología, Buenos Aires; Argentina.Fil: Romanin, Viviana. Hospital de Niños Ricardo Gutierrez, Epidemiología, Buenos Aires; Argentina.Fil: Regueira, Mabel. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Chiavetta, Laura. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Agudelo, Clara Inés. Instituto Nacional de Salud, Bogotá; Colombia.Fil: Castañeda, Elizabeth. Instituto Nacional de Salud, Bogotá; Colombia.Fil: De la Hoz, Fernando. Facultad de Medicina, Departamento de Salud Pública, Universidad Nacional de Colombia, Bogotá; Colombia.Fil: Higuera, Ana Betty. Secretaria de Salud de Bogotá, Bogotá; Colombia.Fil: Arce, Patricia. Secretaria de Salud de Bogotá, Bogotá; Colombia.Fil: Cohen, Adam L.. National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA; Estados Unidos.Fil: Verani, Jennifer. National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA; Estados Unidos.Fil: Zuber, Patrick. Department of Immunization, Vaccines and Biologicals, World Health Organization, Geneva; Suiza.Fil: Gabastou, Jean-Marc. Pan American Health Organization, Washington DC; Estados Unidos.Fil: Pastor, Desiree. Pan American Health Organization, Washington DC; Estados Unidos.Fil: Flannery, Brendan. Pan American Health Organization, Washington DC; Estados Unidos.Fil: Andrus, Jon. Pan American Health Organization, Washington DC; Estados Unidos.To inform World Health Organization recommendations regarding use of Haemophilus influenzae type b (Hib) vaccines in national immunization programs, a multi-country evaluation of trends in Hib meningitis incidence and prevalence of nasopharyngeal Hib carriage was conducted in four South American countries using either a primary, three-dose immunization schedule without a booster dose or with a booster dose in the second year of life. Surveillance data suggest that high coverage of Hib conjugate vaccine sustained low incidence of Hib meningitis and low prevalence of Hib carriage whether or not a booster dose was used

Vigilancia de Neisseria meningitidis en Argentina, 1993-2005: distribución de serogrupos, serotipos y serosubtipos causantes de enfermedad invasiva Surveillance of Neisseria meningitidis in Argentina, 1993-2005: Distribution of serogroups, serotypes and serosubtypes isolated from invasive disease

Neisseria meningitidis es agente causal de enfermedades severas como meningitis, bacteriemia y síndrome de shock séptico. Se presenta la distribución en serogrupos, serotipos y serosubtipos de 2244 aislamientos de N. meningitidis obtenidos de cuadros de meningitis y/o meningococcemia durante el período 1993-2005 y analizados en el Laboratorio Nacional de Referencia del INEI-ANLIS "Dr. Carlos G. Malbrán". Estos aislamientos eran provenientes de 33 hospitales de todo el país, conformados en una red nacional de laboratorios para el estudio de meningitis bacteriana. Durante el período 1993-1995 prevaleció el serogrupo B (66%), mientras que entre los años 1995 y 2001 prevaleció el serogrupo C (65%); a partir de esta fecha se restableció la prevalencia de B. En los últimos 5 años los serogrupos Y y W135 representaron en su conjunto el 15,6%, mientras que hasta el año 2000 no superaron el 4,7%. Se registró mayor diversidad en la distribución de serotipos y serosubtipos dentro del serogrupo B que dentro del serogrupo C. Los aislamientos no subtipables durante todo el período de estudio representaron el 52,8%; este elevado porcentaje evidencia la limitada capacidad de la serología para la determinación de subtipos de meningococo.Neisseria meningitidis is an important cause of meningitis, bacteremia and septic shock syndrome. We herein present the distribution of serogroups, serotypes and serosubtypes of 2244 isolates of N. meningitidis from patients with meningitis or meningococcemia, received within the period 1993-2005, in the National Reference Laboratory, INEI-ANLIS "Dr. Carlos G. Malbrán", from 33 Argentine hospitals that are included in a National Network devoted to for the study of bacterial meningitis. Between 1993-1995, serogroup B was prevalent (66%) whereas in the period from 1995-2001, serogroup C prevailed (65%). However, following but after that period, the prevalence of serogroup B was recovered. In the last 5 years of the studied period, the serogroups Y and W135 represented as a whole a 15.6% as a whole whereas up to the year 2000 during the first 6 years they accounted for it was of 4.7%. Higher diversity in the distribution of serotypes and serosubtypes was observed within serogroup B. The nonsubtypable isolates throughout the period of study represented the 52.8%, this high percentage demonstrates the limited capacity of the serotyping for the determination of meningococcal/meningococcus subtypes. of meningococco