Incidencia de la deficiencia de glucosa-6-fosfato deshidrogenasa en un programa de tamiz metabólico ampliado a nivel estatal

Antecedentes La deficiencia de glucosa 6-fosfato-deshidrogenasa es la enfermedad enzimática eritrocitaria más común, con una prevalencia de 400 millones de personas en el mundo. Esta deficiencia presenta una herencia recesiva de patrón ligado a X. El tratamiento fundamental se basa en la prevención del agente externo desencadenante. En algunos países la detección de esta deficiencia se encuentra dentro del tamiz metabólico, no así en nuestra región. Por lo tanto, en México no se conoce bien la incidencia de esta condición. El objetivo de este trabajo fue estimar la incidencia de la deficiencia de G6PD en una población de recién nacidos en Nuevo León. Materiales y Métodos Estudio retrospectivo longitudinal realizado en recién nacidos tamizados de los hospitales de Secretaria de Salud de Nuevo León en un periodo comprendido entre el 2012 al 2015. La recolección de las muestras de sangre en papel filtro para el análisis se obtuvo de la punción de talón. Estas muestras fueron enviadas y procesadas en el laboratorio de Genética Bioquímica del Hospital Universitario “José Eleuterio González”. Se cuantificó la actividad de la 7 enzima G6PD por medio de inmunofluorescencia (Kit Delfia, Perkin Elmer). Los casos que resultaron positivos fueron confirmados con una segunda cuantificación de la actividad de la enzima. Resultados Se incluyeron un total de 96,152 recién nacidos tamizados en los hospitales de la Secretaría de Salud de Nuevo León. En un primer análisis resultaron positivos para la deficiencia 566 pacientes. A los casos positivos, se les solicitó una segunda muestra para la confirmación de la deficiencia, recibiendo 469 (82% del total de los positivos). Con esto confirmaron 384 pacientes deficientes de G6PD, reportando así una incidencia de 3.9 casos por cada 1,000 recién nacidos tamizados. Conclusiones Al comprar nuestros resultados con otros estudios similares de México, se reporta una incidencia más alta. Se debe tener en cuenta el aumento progresivo de la migración de personas que pudiera impactar en esto, así mismo la diversidad genética de nuestra región. Dado que el tratamiento se basa en la prevención, el diagnóstico temprano de esta patología nos permitirá ofrecer información para la prevención de las crisis antes de que sucedan. Por lo cual se propone realizar estudios de costo – beneficio para establecer la inclusión de esta enfermedad en el tamiz metabólico que se realiza en el país

Aplicación del mantenimiento preventivo para aumentar la productividad de acopio de cilindros vacíos de GLP en la empresa Reparto Perú S.A.C. Ventanilla – 2019

El presente proyecto de investigación se realiza al observar que la empresa Reparto Perú S.A.C., operador logístico encargado del envasado, transporte y distribución de GLP, presenta inconvenientes perjudiciales en el transporte logístico de los cilindros, específicamente en el área de la “operación canje” afectando la productividad de esta organización. En este estudio su objetivo principal es Determinar como el mantenimiento preventivo aumenta la productividad de acopio de los cilindros vacíos de GLP en la empresa Reparto Perú S.A.C. Ventanilla, 2019. Por otro lado, en el desarrollo del proyecto se desarrollará la importancia del mantenimiento en la empresa, las fallas de cada unidad para saber en qué estado se encuentran las unidades, y así mismo, arreglarlo o comprar nuevas piezas. Además, el tipo de investigación es aplicada, su diseño de investigación es cuasi experimental, y el nivel de investigación explicativo. En la población se consideró 8 unidades con las que cuenta la empresa Reparto Perú S.A.C., durante 26 días. La muestra está constituida por las 3 unidades críticas de la empresa. La investigación concluye que la aplicación del mantenimiento aumenta la productividad de acopio de los cilindros vacíos de GLP en la empresa Reparto Perú S.A.C., Ventanilla, 2019, incrementando la productividad en 15%, la eficiencia en 6% y la eficacia en 15%

Twist: A Regulator of Epithelial-Mesenchymal Transition in Lung Fibrosis

BACKGROUND: Several studies have implicated viral infection as an important factor in the pathogenesis of IPF and related fibrotic lung disorders. Viruses are thought to cause epithelial cell injury and promote epithelial-mesenchymal transition (EMT), a process whereby differentiated epithelial cells undergo transition to a mesenchymal phenotype, and considered a source of fibroblasts in the setting of lung injury. We have demonstrated an association between the epithelial injury caused by chronic herpes virus infection with the murine gamma-herpes virus, MHV68, and lung fibrosis. We hypothesize that EMT in this model of virus-induced pulmonary fibrosis is driven by the expression of the transcription factor Twist. METHODS/FINDINGS: In vitro MHV68 infection of murine lung epithelial cells induced expression of Twist, and mesenchymal markers. Stable overexpression of Twist promoted EMT in MLE15 lung epithelial cells. Transient knockdown expression of Twist resulted in preservation of epithelial phenotype after in vitro MHV68 infection. In concordance, high expression of Twist was found in lung epithelial cells of MHV68 infected mice, but not in mock infected mice. Alveolar epithelial cells from lung tissue of idiopathic pulmonary fibrosis (IPF) patients were strongly positive for Twist. These cells demonstrated features of EMT with low expression of E-cadherin and upregulation of the mesenchymal marker N-cadherin. Finally, IPF tissue with high Twist protein levels was also positive for the herpesvirus, EBV. CONCLUSIONS/SIGNIFICANCE: We conclude that Twist contributes to EMT in the model of virus-induced pulmonary fibrosis. We speculate that in some IPF cases, gamma-herpes virus infection with EBV might be a source of injury precipitating EMT through the expression of Twist

Tolvaptan in ADPKD Patients With Very Low Kidney Function

Introduction: Tolvaptan slowed estimated glomerular filtration rate (eGFR) decline in subjects with autosomal dominant polycystic kidney disease (ADPKD) in TEMPO 3:4 and REPRISE trials. Tolvaptan effects in subjects with eGFR 15 to 24 ml/min per 1.73 m2 were not investigated. This post hoc analysis retrospectively investigated eGFR decline in REPRISE versus an open-label, phase 3b extension trial (open-label extension [OLE] NCT02251275) in subjects who received placebo in REPRISE and tolvaptan in OLE with eGFR 15 to 24 and 25 to 29 ml/min per 1.73 m2, respectively. Methods: One data subset comprised subjects with OLE baseline eGFR 15 to 29 ml/min per 1.73 m2 who had received placebo in REPRISE and began tolvaptan in OLE. The second comprised subjects who had received tolvaptan in REPRISE and were matched to REPRISE placebo-treated subjects for REPRISE baseline characteristics. Annualized eGFR slopes in REPRISE versus OLE were compared within the REPRISE placebo (i.e., placebo vs. tolvaptan treatment) and tolvaptan (i.e., 2 periods of tolvaptan treatment) subsets. Results: Mean annualized eGFR slopes (ml/min per 1.73 m2) during tolvaptan treatment in OLE versus placebo treatment in REPRISE were -3.4 versus -5.2 for subjects with OLE baseline eGFR 15 to 29 (difference, 1.7; P < 0.001), -3.6 versus -5.4 with baseline eGFR 15 to 24 (difference, 1.8; P < 0.001), and -3.3 versus -4.9 with baseline eGFR 25 to 29 (difference, 1.6; P < 0.001). In REPRISE tolvaptan subjects who continued tolvaptan in OLE, treatment effect was maintained (no difference between mean annualized eGFR slopes). Conclusion: Initiating or maintaining tolvaptan therapy significantly delayed eGFR decline in subjects with baseline eGFR 15 to 24 and 25 to 29 ml/min per 1.73 m2

Range and variability of outcomes reported in randomized trials conducted in patients with polycystic kidney disease: A systematic review

Rationale & Objective: Trials in autosomal dominant polycystic kidney disease (ADPKD) have increased, but their impact on decision making has been limited. Because heterogeneity in reported outcomes may be responsible, we assessed their range and variability in ADPKD trials. Study Design: Systematic review. Setting & Study Population: Adult participants in clinical trials in ADPKD. Selection Criteria for Studies: We included trials that studied adults and were published in English. For trials that enrolled patients without ADPKD, only those enrolling ≥50% of participants with ADPKD were included. Data Extraction: We extracted information on all discrete outcome measures, grouped them into 97 domains, and classified them into clinical, surrogate, and patient-reported categories. For each category, we choose the 3 most frequently reported domains and performed a detailed analysis of outcome measures. Analytical Approach: Frequencies and characteristics of outcome measures were described. Results: Among 68 trials, 1,413 different outcome measures were reported. 97 domains were identified; 41 (42%) were surrogate, 30 (31%) were clinical, and 26 (27%) were patient reported. The 3 most frequently reported domains were in the surrogate category: kidney function (54; 79% of trials; using 46 measures), kidney and cyst volumes (43; 63% of trials; 52 measures), and blood pressure (27; 40% of trials, 30 measures); in the clinical category: infection (10; 15%; 21 measures), cardiovascular events (9; 13%; 6 measures), and kidney failure requiring kidney replacement therapy (8; 12%; 5 measures); and in the patient-reported category: pain related to ADPKD (16; 24%; 26 measures), pain for other reasons (11; 16%; 11 measures), and diarrhea/constipation/gas (10; 15%; 9 measures). Limitations: Outcome measures were assessed for only the top 3 domains in each category. Conclusions: The outcomes in ADPKD trials are broad in scope and highly variable. Surrogate outcomes were most frequently reported. Patient-reported outcomes were uncommon. A consensus-based set of core outcomes meaningful to patients and clinicians is needed for future ADPKD trials

SÍNDROMES DE DISPERSÃO DE ESPÉCIES DE CAATINGA DA CHAPADA DO ARARIPE

O sucesso na dispersão das sementes é de grande importância para a reprodução das plantas, os tipos de dispersão estão associados a características morfológicas de frutos e sementes, sendo assim cada planta possui o tipo de dispersão que possibilite mais chances das sementes alcançarem um lugar com todas as condições necessárias para a sua germinação. O conhecimento acerca dessas características (síndromes) subsidiam políticas de conservação, deste modo, com este trabalho o objetivo foi realizer um compilamento de espécies de Caatinga com respectivos tipos de frutos e de síndromes de dispersão. O estudo englobou áreas de Caatinga existentes na Chapada do Araripe, a qual compreende parte dos estados de Ceará, Pernambuco e Piauí e foi pautado em revisão de literature. Com base nos dados obtidos foram relacionadas 265 espécies, distribuídas em 65 famílias botânicas com destaque para Fabaceae (40 ssp.), Rubiaceae (17ssp.) e Bignoniaceae (16 ssp.). O hábito com maior representação foi o arbustivo, englobando 104 espécies (39,2%) e arbóreo 47 (17,7%). A zoocoria foi a síndrome de dispersão mais frequente (50,5%), representada por 134 das espécies. A cápsula foi o tipo de fruto mais representativo sendo descrito para 83 (31,3%) das espécies compiladas. Os dados revelam que ainda são escassos estudos relacionados as síndromes de dispersão em áreas de Caatinga no Ceará, a despeito de sua rica biodiversidade e da importãncia dos mesmos para o entendimento da dinâmica desse ambiente. Os resultados reafirmam a estreita relação envolvendo flora e fauna e consequente importância do desenvolvimento de políticas publicas voltadas a proteção desse ambiente.

Multicenter, open-label, extension trial to evaluate the long-term efficacy and safety of early versus delayed treatment with tolvaptan in autosomal dominant polycystic kidney disease:The TEMPO 4:4 Trial

Background.: In TEMPO 3:4, the vasopressin V2 receptor antagonist tolvaptan slowed total kidney volume (TKV) growth and estimated glomerular filtration rate (eGFR) decline relative to placebo. Methods.: TEMPO 4:4 was designed to provide an additional 2 years of data on the long-term safety and efficacy of tolvaptan in subjects completing TEMPO 3:4. The objective was to assess the disease-modifying effects of tolvaptan on TKV and eGFR end-points including change from baseline over the combined duration of TEMPO 3:4 and TEMPO 4:4, and non-inferiority of slopes during TEMPO 4:4. Results.: Of the 1445 subjects randomized to TEMPO 3:4, 871 (60.3%) enrolled in TEMPO 4:4. Percent changes in TKV from TEMPO 3:4 baseline to TEMPO 4:4 Month 24 were 29.9% and 31.6% (prior tolvaptan versus prior placebo, P = 0.38). Adjusting for baseline covariates improved the TKV treatment difference at Month 24 in TEMPO 4:4 from -1.70% to - 4.15% between the groups (P = 0.04). Slopes of TKV growth during TEMPO 4:4 were higher in early- versus delayed-treatment groups (6.16% versus 4.96% per year, P = 0.05). Analysis of secondary eGFR endpoints demonstrated a persistent effect on eGFR (3.15 mL/min/1.73 m 2 , P < 0.001), and non-inferiority in eGFR slopes. The safety profile on exposure to tolvaptan in TEMPO 4:4 was similar to that in TEMPO 3:4. Conclusions.: The results of TEMPO 4:4 support a sustained disease-modifying effect of tolvaptan on eGFR. The lack of a sustained treatment difference on TKV may be accounted for by limitations of the trial design, including loss of randomization and baseline imbalances ensuing TEMPO 3:4. The safety profile was similar to that observed in TEMPO 3:4

Analysis of baseline parameters in the HALT polycystic kidney disease trials

HALT PKD consists of two ongoing randomized trials with the largest cohort of systematically studied patients with autosomal dominant polycystic kidney disease to date. Study A will compare combined treatment with an angiotensin-converting inhibitor and receptor blocker to inhibitor alone and standard compared with low blood pressure targets in 558 early-stage disease patients with an eGFR over 60ml/min per 1.73m2. Study B will compare inhibitor-blocker treatment to the inhibitor alone in 486 late-stage patients with eGFR 25–60ml/min per 1.73m2. We used correlation and multiple regression cross-sectional analyses to determine associations of baseline parameters with total kidney, liver, or liver cyst volumes measured by MRI in Study A and eGFR in both studies. Lower eGFR and higher natural log-transformed urine albumin excretion were independently associated with a larger natural log–transformed total kidney volume adjusted for height (ln(HtTKV)). Higher body surface area was independently associated with a higher ln(HtTKV) and lower eGFR. Men had larger height-adjusted total kidney volume and smaller liver cyst volumes than women. A weak correlation was found between the ln(HtTKV) and natural log–transformed total liver volume adjusted for height or natural log liver cyst volume in women only. Women had higher urine aldosterone excretion and lower plasma potassium. Thus, our analysis (1) confirms a strong association between renal volume and functional parameters, (2) shows that gender and other factors differentially affect the development of polycystic disease in the kidney and liver, and (3) suggests an association between anthropomorphic measures reflecting prenatal and/or postnatal growth and disease severity

Fab-based bispecific antibody formats with robust biophysical properties and biological activity

A myriad of innovative bispecific antibody (BsAb) platforms have been reported. Most require significant protein engineering to be viable from a development and manufacturing perspective. Single-chain variable fragments (scFvs) and diabodies that consist only of antibody variable domains have been used as building blocks for making BsAbs for decades. The drawback with Fv-only moieties is that they lack the native-like interactions with CH1/CL domains that make antibody Fab regions stable and soluble. Here, we utilize a redesigned Fab interface to explore 2 novel Fab-based BsAbs platforms. The redesigned Fab interface designs limit heavy and light chain mixing when 2 Fabs are co-expressed simultaneously, thus allowing the use of 2 different Fabs within a BsAb construct without the requirement of one or more scFvs. We describe the stability and activity of a HER2×HER2 IgG-Fab BsAb, and compare its biophysical and activity properties with those of an IgG-scFv that utilizes the variable domains of the same parental antibodies. We also generated an EGFR × CD3 tandem Fab protein with a similar format to a tandem scFv (otherwise known as a bispecific T cell engager or BiTE). We show that the Fab-based BsAbs have superior biophysical properties compared to the scFv-based BsAbs. Additionally, the Fab-based BsAbs do not simply recapitulate the activity of their scFv counterparts, but are shown to possess unique biological activity

Turismo y Género. Una mirada desde Iberoamérica

En las últimas cuatro décadas ha crecido el interés de la academia, gobiernos y organizaciones internacionales por estudiar cómo ha sido, en qué circunstancias y qué efectos ha traído la incorporación de las mujeres al turismo. De esta forma se inicia un debate internacional en el que se cuestionan, por un lado, los efectos negativos de esta actividad en la vida de las mujeres y, por el otro, se realzan beneficios económicos que mejoran su calidad de vida y la de sus familias. A pesar del interés y la importante participación de mujeres en el sector turístico, aún son insuficientes los estudios enfocados en explicar y evidenciar su situación laboral. En este contexto, surge la idea de publicar un libro que compilara trabajos recientes en torno a las condiciones de las trabajadoras en el sector turístico de Iberoamérica.Esta obra se compone de tres secciones, Aproximaciones teórico metodológicas, Mujer y turismo en zonas rurales y La mujer en empresas turísticas, cuyas investigaciones abordan distintos temas para evidenciar los problemas enfrentados por las mujeres, proponer diversas soluciones y comprender su escenario laboral. En la primera sección, hay dos capítulos que proponen marcos teóricos para analizar el empoderamiento de las mujeres en el turismo rural. Los resultados de investigaciones de la segunda sección visibilizan las desigualdades, reflexionan y proponen acciones para mejorar las condiciones de las trabajadoras turísticas. En la última, en los tres capítulos, concentrados en las actividades empresariales, se estudian las desventajas y obstáculos de la empleada en alguna compañía turística.Universidad Autónoma del Estado de México