Ultrabiomicroscopic-Histopathologic Correlations in Individuals with Autosomal Dominant Congenital Microcoria: Three-Generation Family Report

Background: Congenital microcoria (CMC) is due to a maldevelopment of the dilator pupillae muscle of the iris, with a pupil diameter of less than 2 mm. It is associated with juvenile open angle glaucoma and myopia. We report on a three-generation Mexican-Mestizo family with CMC. The eldest member’s iris biopsy proved muscle anomalies. Further, we analyzed novel ultrasound biomicroscopy findings in the family members who did not require surgery. Patients and Methods: A 62-year-old woman, her 41-year-old son and her 9-year-old grandson affected with microcoria since birth, documented by clinical examination and ultrasound biomicroscopy. The eldest member underwent phacoemulsification, and a biopsy of the iris and the anterior capsule of the lens was taken. Results: Ultrasound biomicroscopy confirmed the CMC diagnosis showing iris thinning and a pupil diameter of less than 2 mm. Histopathology of the iris showed a significant reduction of smooth muscle cells, but no alterations of the anterior lens capsule. Discussion: Although CMC is a rare disorder, which is due to a maldevelopment of the dilator pupillae muscle of the iris, it could be associated with juvenile open angle glaucoma and myopia; therefore, precise diagnosis is required. Ultrasound biomicroscopy could be a great option to confirm the disorder

Reflexiones desde la enseñanza y el aprendizaje de la arquitectura 2

La segunda entrega del libro Doceo “Reflexiones desde la enseñanza y el aprendizaje de la arquitectura”, es fruto de metodologías de enseñanza- aprendizaje diseñadas para cada caso, y que representan la impronta personal de cada autor. Es importante resaltar, que todos los argumentos presentados en esta obra corresponden a experiencias en el aula, conclusiones de docentes y/o estudiantes en el marco de una asignatura desarrollada en la Universidad de la Costa con sede en Barranquilla, Colombia. El Volumen dos de esta entrega se ha editado progresivamente, en una primera parte la compilación estuvo a cargo de la profesora Stephania Mouthon, quien centralizó todos los manuscritos, luego de esto, hemos construido de manera conjunta el diseño editorial, estructura del cuerpo y demás aspectos de perfeccionamiento del documento.Departamento de Arquitectura, Universidad de la Cost

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Post Covid-19 health: implementation of the Minsa communication strategy for the National Prevention Week “Chequéate Perú”, carried out between the months of April and May 2023

El presente Trabajo de Suficiencia Profesional describe la estrategia de comunicación que desarrolló e implementó la Oficina de Comunicaciones del Ministerio de Salud (Minsa) con motivo de la campaña Semana Nacional de la Prevención “Chequéate Perú”. La campaña se desarrolló entre abril y mayo de 2023, y la estrategia de comunicación diseñada tuvo como objetivos informar a la ciudadanía sobre los pormenores de la campaña, promover la importancia del chequeo preventivo y sensibilizar a los aliados estratégicos para que se sumen a esta iniciativa nacional, con el fin de generar involucramiento y compromiso para potenciar acciones conjuntas que beneficien a la población. La experiencia profesional que se toma como punto de referencia para este trabajo es la de Scarlet Reyes, quien integró el equipo de comunicaciones del Minsa y participó del desarrollo de la citada estrategia de comunicación en sus cuatro etapas: lanzamiento, desarrollo, cierre y mantenimiento de la cultura preventiva. Para los fines de este trabajo, se toma como unidad de análisis un conjunto de acciones de comunicación realizadas durante las tres primeras etapas de la estrategia. La última no se considera en el estudio debido a que al término del trabajo continúa en desarrollo. El estudio de las piezas de comunicación dejó interesantes hallazgos que dan cuenta de una estrategia minuciosamente planificada, que buscó desde un inicio conectar de forma empática con su público objetivo, empleando para ello recursos y herramientas en la construcción de mensajes que generaron identificación, emociones y, sobre todo, la respuesta esperada en la ciudadanía en relación con su salud preventiva.This professional proficiency work describes the communication strategy that was developed and implemented by the Communications Office of the Ministry of Health as part of the preventive campaign National Prevention Week “Chequéate Perú”. This campaign was developed between April and May 2023, and the communication strategy designed had the objectives of informing citizens about the details of the campaign, promoting the importance of preventive check-ups and raising awareness among strategic allies so that they can join to this national initiative, generating involvement and commitment to promote joint actions that benefit the population. The professional experience that is taken as a reference point for this work comes from Scarlet Reyes, who was part of the communications team and participated in the development of the aforementioned communication strategy, which was composed of four stages: launch, development, closure and maintenance of the preventive culture. For the purposes of this academic work, a set of communication actions that were carried out during the first three stages of the strategy are taken as a unit of analysis. The last one is not considered in this study because, at the end of this academic work, it is still ongoing. The study of the communication pieces left interesting findings that show a carefully planned strategy, which sought from the start to connect empathically with its target audience, using resources and tools in the construction of messages that generated identification, emotions and, above all, the expected response from citizens in relation to taking action for their preventive health.Trabajo de suficiencia profesiona

Public Urban Transportation in the Smart City: An Exploratory Study in the Northern México

Upon identifying the troubled system of public transportation in the Northern-border City of Juarez, Mexico, this research adopts an exploratory approach to address such problem and provide a plausible path to solve it. Urban mobility has become one of the main challenges for the Smart City. The latter concept is a global tendency to achieve competitive edge via adopting technological development regarding public mobility. Juarez system of public transportation experiences lacks of modernity infrastructure, which results in pollution due to obsolete vehicles, delays, passenger saturation during heavy hours, traffic accidents and users’ inconveniences. Although many proposals arose in the past to deal with the prevailing situation, to date the city experiences no improvements whatsoever. This paper examines what the scenario would be if the City embarked in the endeavor of adopting high-tech vehicles for public transportation. Particularly, the paper transits through the sate-of-the-art literature to provide in-sights regarding modern transportation alternatives that not only are environmental-friendly, but also financially viable, promoting productive chaining and local benefits. The proposal centers in buses powered by electricity. The paper discusses financial figures and possible scenarios; it also highlights the need for future urban infrastructure improvement and reconfigurations, especially pavement and transportation routes redesign to allocate charging stations

Análisis de la eficiencia del Programa de Complementación Alimentaria (PCA) en la reducción del hambre de la población pobre en la provincia de Cañete en el período 2013-2017

La presente investigación busca identificar los resultados del funcionamiento del Programa de Complementación Alimentaria (en adelante PCA), modalidad de Comedores Populares, en la reducción del hambre de la población en situación de pobreza en la provincia de Cañete, y entre el periodo comprendido del 2013 al 2017. El PCA es un programa social que funciona a través de convenios de gestión propuestos por el MIDIS, acuerdan transferencias de recursos, asistencia y monitoreo, y que la otra parte (la Municipalidad Provincial de Cañete) brinda canastas alimentarias a dichos Comedores, que a su vez, entregan raciones preparadas a sus usuarios/as. El problema radica en que el Estado peruano ha gastado millones de soles en programas sociales de tipo asistencialistas (protectores), como principalmente el PCA, que busca mejorar el acceso a la alimentación (evitando la subalimentación) de la población en situación de pobreza en el país; por tanto, resulta importante conocer sus resultados en la provincia de Cañete, y a la vez recomendar mejoras para incrementar su eficiencia y su sostenibilidad. Además, la ejecución del presente estudio se desarrolló bajo el tipo cualitativo, y las técnicas utilizadas son: elaboración e interpretación de cuadros estadísticos; análisis tanto de los paradigmas, de los objetivos del PCA, informes oficiales, y entrevistas directas a los/as usuarios/os y gestores del PCA, así como otros actores. Dentro de las conclusiones alcanzadas se ha determinado que el PCA, en su modalidad Comedores Populares, tiene debilidades; por tanto, su estructura y su funcionamiento es ineficiente, debido a que el 96% de las madres consideran inadecuada la infraestructura de su Comedor (no se considera digna, segura, y con todos servicios) para su óptimo funcionamiento; además se entrega la canasta alimentaria solo 8 meses del año; por su parte, el monto destinado de presupuesto por usuario/a representa en promedio solo es el 4.7% del valor mínimo de la canasta básica de alimentos per cápita mensual (nacional) es decir del valor de la línea de pobreza; asimismo, el mismo presupuesto mensual por usuario/a del comedor solo cubriría el 8,8% del valor de la línea de pobreza extrema. Se agrega que, solo se supervisa el funcionamiento del 23.5% del total de comedores cada mes y no incluye la valoración del estado nutricional de las/os usuarias/os, entre otros indicadores de resultados. Asimismo, la población pobre de la provincia representa en promedio el 13.91% de la población total de Cañete, también en el periodo de estudio se ha incrementado el total de pobres en un 5.8%; sin embargo la cobertura del PCA (modalidad comedores populares) de su público objetivo (población en situación de pobreza), solo ha alcanzado el 13.2%. Además, se estima que las personas que padecen déficit calórico y que sufren de inseguridad alimentaria moderada o grave, alcanzaron el 25.6% y el 40.9% de la población provincial, respectivamente; igualmente estos indicadores se incrementaron en el 2017, para el primero en un 3.6% respecto al 2013 y para el segundo en un 16.8% al 2015; a la par, la cobertura del PCA respecto a los indicadores de hambre, solo alcanzan a un 7.2% de las personas que padecen déficit calórico y a un 4.4% de las que sufren de inseguridad alimentaria moderada o grave en la provincia de Cañete, respectivamente. En general, se evidencia que en el periodo de estudio, el funcionamiento del PCA, modalidad comedores, tiene debilidades en su estructura y con resultados ineficientes y de baja cobertura respecto a su público objetivo; y consecuentemente no ha logrado influir en la reducción del hambre de las personas pobres de la provincia de Cañete, muy por el contrario los indicadores señalados se han incrementado entre los años 2013 al 2017; lo que obliga al Estado a implementar cambios urgentes en su diseño y ejecución en beneficio de las personas en situación de vulnerabilidad de la provincia de Cañete y del país

Therapeutic Effects of WT1 Silencing via Respiratory Administration of Neutral DOPC Liposomal-siRNA in a Lung Metastasis Melanoma Murine Model

The lungs represent a frequent target for metastatic melanoma as they offer a high-oxygen environment for tumor development. The overexpression of the WT1 protein has been associated with the occurrence of melanoma. In this study, we evaluated the effects of silencing the WT1 protein by siRNA in both in vitro in the B16F10 melanoma cell line and in vivo in a murine model of lung metastatic melanoma. We did this by implementing a novel respiratory delivery strategy of a neutral DOPC liposomal-siRNA system (L-siRNA). In vitro studies showed an effective silencing of the WT1 protein in the siRNAs’ WT1-treated cells when compared with controls, resulting in a loss of the cell’s viability and proliferation by inducing G1 arrest, the inhibition of the migration and invasion capacities of the cells, as well as the induction of apoptosis. In vivo, the respiratory administration of L-WT1 siRNA showed an efficient biodistribution on the lungs. After two weeks of treatment, the silencing of the WT1 protein resulted in an important antitumor activity that reduced the tumor weight. In the survival study, L-WT1 treatment could significantly delay the death of the animals. This work demonstrates the efficacy of the L-siRNA respiratory administration as a novel therapy to reduce pulmonary tumors and to increase survivability by silencing specific cancer oncogenes as WT1

Exosomes: From Garbage Bins to Promising Therapeutic Targets

Intercellular communication via cell-released vesicles is a very important process for both normal and tumor cells. Cell communication may involve exosomes, small vesicles of endocytic origin that are released by all types of cells and are found in abundance in body fluids, including blood, saliva, urine, and breast milk. Exosomes have been shown to carry lipids, proteins, mRNAs, non-coding RNAs, and even DNA out of cells. They are more than simply molecular garbage bins, however, in that the molecules they carry can be taken up by other cells. Thus, exosomes transfer biological information to neighboring cells and through this cell-to-cell communication are involved not only in physiological functions such as cell-to-cell communication, but also in the pathogenesis of some diseases, including tumors and neurodegenerative conditions. Our increasing understanding of why cells release exosomes and their role in intercellular communication has revealed the very complex and sophisticated contribution of exosomes to health and disease. The aim of this review is to reveal the emerging roles of exosomes in normal and pathological conditions and describe the controversial biological role of exosomes, as it is now understood, in carcinogenesis. We also summarize what is known about exosome biogenesis, composition, functions, and pathways and discuss the potential clinical applications of exosomes, especially as biomarkers and novel therapeutic agents