Adherencia al control prenatal en la Clínica de Gestantes Adolescentes del Hospital de Engativá de Bogota

La frecuencia del embarazo durante la adolescencia en el país ha sido calificado como un problema de salud pública. Objetivo: evaluar los efectos de la consulta dirigida a Adolescencia en la calidad del control prenatal, en términos de: edad gestacional de inicio, asistencia y cumplimiento del mismo Tipo de estudio: observacional de cohortes retrospectivo. Metodología: pacientes adolescentes que se les realizó el control prenatal y se les atendió parto en el Hospital de Engativá de Bogotá - Colombia, entre el 15 de enero de 2010 y el15 de enero de 2011, comparando dos cohortes de pacientes: las que asistieron a la clínica de gestantes adolescentes y las adolescentes gestantes que asistieron a control prenatal por el especialista que no hacen parte de la clínica de gestantes adolescentes. Resultados: El número de controles prenatales fue significativamente mayor (más de 4 consultas) en el grupo de pacientes que asistieron a la clínica de gestantes adolescentes, (RR 1.87 IC 95% 1.26 – 2.76 P 0.001). Se evaluaron el cumplimiento de algunas recomendaciones del control prenatal y dos desenlaces obstétricos (bajo peso al nacer y parto pretérmino), entre los grupos sin encontrar diferencia significativa. Conclusiones: Se encontró en este estudio que una consulta especial y dedicada al control de la gestante adolescente mejora significativamente la asistencia al control prenatal en comparación a un control convencional. / Abstract. The frequency of teenage pregnancy in the country has been classified as a public health problem. Objective: evaluate the effects of consultation aimed at teenagers in the quality of antenatal care in terms of: gestational age of onset, assistance and enforcement thereof. Type of study: Retrospective observational cohort. Methodology: adolescent patients who underwent prenatal care and childbirth are attended Engativá Hospital in Bogota - Colombia, between January 15, 2010 and January 15, 2011 comparing two cohorts of patients: those who attended clinic pregnant adolescents and adolescent pregnant women who attended antenatal care by specialists who are not part of the clinic for pregnant adolescents. Results: The number of prenatal visits was significantly higher (more than 4 visits) in the group of patients attending the clinic for pregnant adolescents (RR 1.87 95% CI 1.26 - 2.76 P 0.001). We evaluated the performance of some recommendations of prenatal and obstetric two outcomes (low birth weight and preterm delivery), between groups found no significant difference. Conclusions: It was found in this study that a special consultation and dedicated to the control of the pregnant teen assistance significantly improved prenatal care compared to conventional control.Otr

Trans regulation in the Ultrabithorax gene of Drosophila: alterations in the promoter enhance transvection

PMCID: PMC556824We report a genetic and molecular study of UbxMX6 and Ubx195rx1, two mutations in the Ultrabithorax (Ubx) locus which appear to have a strong effect on the activity of the homologous Ubx gene. These mutations show the characteristic embryonic and adult phenotypes of Ubx null alleles, and also fail to produce any detectable Ubx product. Yet, genetic and phenotypic analyses involving a large number of trans heterozygous combinations of UbxMX6 and Ubx195rx1 with different classes of Ubx mutations, indicate that they hyperactivate the homologous gene. This effect is induced on wildtype or mutant forms of Ubx, provided that the pairing in the bithorax region is normal, i.e. these mutations have a strong positive effect on transvection. We also show that, unlike all the other known cases of transvection in Ubx, this is not zeste-dependent. Southern analyses indicate that UbxMX6 is a 3.4 kb deletion, and Ubx195rx1 is an approximately 11 kb insertion of foreign DNA, both in the promoter region. We speculate that the region altered in the mutations may have a wildtype function to ensure cis-autonomy of the regulation of Ubx transcription.This work was supported by grants from the DGICYT and the Fundación Ramón Areces.Peer reviewe

Real-world effectiveness of caplacizumab vs the standard of care in immune thrombotic thrombocytopenic purpura

Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. The objective of this study was to analyze and compare the safety and efficacy of caplacizumab vs the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 patients with iTTP (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5%; P <.05) and less refractoriness (4.5% vs 14.1%; P <.05) than those who were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after PEX was associated with a lower number of PEX (odds ratio, 7.5; CI, 2.3-12.7; P <.05) and days of hospitalization (odds ratio, 11.2; CI, 5.6-16.9; P <.001) compared with standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared with the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared with standard of care regimens. When administered within the first 3 days after PEX, it also provided a faster clinical response, reducing hospitalization time and the need for PEX

Real-world effectiveness of caplacizumab vs the standard of care in immune thrombotic thrombocytopenic purpura

Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. The objective of this study was to analyze and compare the safety and efficacy of caplacizumab vs the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 patients with iTTP (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5%; P < .05) and less refractoriness (4.5% vs 14.1%; P < .05) than those who were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after PEX was associated with a lower number of PEX (odds ratio, 7.5; CI, 2.3-12.7; P < .05) and days of hospitalization (odds ratio, 11.2; CI, 5.6-16.9; P < .001) compared with standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared with the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared with standard of care regimens. When administered within the first 3 days after PEX, it also provided a faster clinical response, reducing hospitalization time and the need for PEX

ANTI M. leprae IgM ANTIBODY DETERMINATION BY ULTRAMICROIMMUNOENZYMATIC (UMELISA HANSEN) FOR THE DIAGNOSIS AND MONITORING LEPROSY

The relationship between the IgM antibody response, antigenic load as well as the clinical improvement after chemotherapy was studied in order to obtain useful data for the early diagnosis and monitoring leprosy. A level of 82% (94/115) agreement was obtained between IgM UMELISA HANSEN and slitskin smear examination. Discrepant results were observed in 16 patients who showed positive IgM response despite negative by the skin smear examination. In these patients, the IgM response was seen to be associated to the early signal for bacilli recurrence in the skin. In one of these patients the presence of bacilli was demonstrated in the skin, two months after IgM antibodies being detected by UMELISA HANSEN. Also in one of the treated patients positive by both diagnostic techniques, a remarkable decrease in the IgM antibody levels was seen, correlating with a significant clinical improvement. Moreover it was found a direct relationship between the IgM antibody response and bacterial antigenic load, regardless the time elapsed in the disease's evolution

Genetic analysis of RNA polymerase I allowed isolation of alleles leading to over-production of rRNA transcripts

Trabajo presentado a la OddPols: International Conference on Transcription by RNA Polymerase I, III, IV and V, celebrada en Toulouse (Francia) del 26 al 29 de junio de 2018.Peer Reviewe

Flexibility of the jaw-lobe region in RNA polymerase I influences transcriptional elongation

Resumen del trabajo presentado al III Meeting Red de Excelencia Temática: "RNA Life", celebrado en Salamanca del 24 al 26 de septiembre de 2018.In growing eukaryotic cells, most transcriptional activity involves synthesis of ribosomal RNA (rRNA) by RNA polymerase I (Pol I). Yeast Pol I is composed by 14 subunits with an overall mass of 600 kDa. Deletion of Pol I subunit A49, which plays a role both in transcription initiation and elongation, causes a severe growth defect. Genetic analysis allowed us to isolate a set of mutants on different Pol I subunits that suppress the A49 deletion phenotype. Most suppressor mutants cluster at the Pol I jaw-lobe region, which encompasses the jaw in subunit A190, the lobe in subunit A135, and the N-terminal and liker domains of subunit A12. We use computational analysis of available Pol I structures to propose a role for the jaw-lobe region in the transition between transcription initiation and elongation. Finally, we show that the most efficient suppressor mutant exhibits increased rRNA production both in vivo and in vitro.Spanish Ministry of Science (BFU2017-87397-P), Ramón Areces Foundation.Peer reviewe

Genetic analyses led to the discovery of a super-active mutant of the RNA polymerase I

Most transcriptional activity of exponentially growing cells is carried out by the RNA Polymerase I (Pol I), which produces a ribosomal RNA (rRNA) precursor. In budding yeast, Pol I is a multimeric enzyme with 14 subunits. Among them, Rpa49 forms with Rpa34 a Pol I-specific heterodimer (homologous to PAF53/CAST heterodimer in human Pol I), which might be responsible for the specific functions of the Pol I. Previous studies provided insight in the involvement of Rpa49 in initiation, elongation, docking and releasing of Rrn3, an essential Pol I transcription factor. Here, we took advantage of the spontaneous occurrence of extragenic suppressors of the growth defect of the rpa49 null mutant to better understand the activity of Pol I. Combining genetic approaches, biochemical analysis of rRNA synthesis and investigation of the transcription rate at the individual gene scale, we characterized mutated residues of the Pol I as novel extragenic suppressors of the growth defect caused by the absence of Rpa49. When mapped on the Pol I structure, most of these mutations cluster within the jaw-lobe module, at an interface formed by the lobe in Rpa135 and the jaw made up of regions of Rpa190 and Rpa12. In vivo, the suppressor allele RPA135-F301S restores normal rRNA synthesis and increases Pol I density on rDNA genes when Rpa49 is absent. Growth of the Rpa135-F301S mutant is impaired when combined with exosome mutation rrp6 and it massively accumulates pre-rRNA. Moreover, Pol I bearing Rpa135-F301S is a hyper-active RNA polymerase in an in vitro tailed-template assay. We conclude that RNA polymerase I can be engineered to produce more rRNA in vivo and in vitro. We propose that the mutated area undergoes a conformational change that supports the DNA insertion into the cleft of the enzyme resulting in a super-active form of Pol I. Author summary The nuclear genome of eukaryotic cells is transcribed by three RNA polymerases. RNA polymerase I (Pol I) is a multimeric enzyme specialized in the synthesis of ribosomal RNA. Deregulation of the Pol I function is linked to the etiology of a broad range of human diseases. Understanding the Pol I activity and regulation represents therefore a major challenge. We chose the budding yeast Saccharomyces cerevisiae as a model, because Pol I transcription apparatus is genetically amenable in this organism. Analyses of phenotypic consequences of deletion/truncation of Pol I subunits-coding genes in yeast indeed provided insights into the activity and regulation of the enzyme. Here, we characterized mutations in Pol I that can alleviate the growth defect caused by the absence of Rpa49, one of the subunits composing this multi-protein enzyme. We mapped these mutations on the Pol I structure and found that they all cluster in a well-described structural element, the jaw-lobe module. Combining genetic and biochemical approaches, we showed that Pol I bearing one of these mutations in the Rpa135 subunit is able to produce more ribosomal RNA in vivo and in vitro. We propose that this super-activity is explained by structural rearrangement of the Pol I jaw/lobe interface