Enhancing photodynamic and radionuclide therapy by small interfering RNA (siRNA)-RAD51 transfection via self-emulsifying delivery systems (SNEDDS).

BACKGROUND AIMS: Gene-silencing by small interfering RNA (siRNA) is an attractive therapy to regulate cancer death, tumor recurrence or metastasis. Because siRNAs are easily degraded, it is necessary to develop transport and delivery systems to achieve efficient tumor targeting. Self-nanoemulsifying systems (SNEDDS) have been successfully used for pDNA transport and delivery, so they may be useful for siRNA. The aim of this work is to introduce siRNA-RAD51 into a SNEDDS prepared with Phospholipon-90G, Labrafil-M1944-CS and Cremophor-RH40 and evaluate its efficacy in preventing homologous recombination of DNA double-strand breaks caused by photodynamic therapy (PDT) and ionizing radiation (IR). METHODS: The siRNA-RAD51 was loaded into SNEDDS using chitosan. Transfection capacity was estimated by comparison with Lipofectamine-2000. RESULTS: SNEDDS(siRNA-RAD51) induced gene silencing effect on the therapies evaluated by cell viability and clonogenic assays using T47D breast cancer cells. CONCLUSIONS: SNEDDS(siRNA-RAD51) shown to be an effective siRNA-delivery system to decrease cellular resistance in PDT or IR.

Effect of pyridoxine or cobalamin supplementation on apoptosis and cell cycle progression in a human glioblastoma cell line.

Glioblastoma is the most aggressive type of brain tumor, with current therapies failing to significantly improve patient survival. Vitamins have important effects on cellular processes that are relevant for tumor development and progression. AIM: The present study explored the effect of pyridoxine or cobalamin supplementation on the viability and cell cycle progression of human glioblastoma cell line U-87 MG. METHOD: Cell cultures were treated with increasing concentrations of pyridoxine or cobalamin for 24-72 h. After supplementation, cell viability and cell cycle progression were assessed by spectrophotometry and flow cytometry. Analysis of Bcl-2 and active caspase 3 expression in supplemented cells was performed by western blot. RESULT: The results show that pyridoxine supplementation decreases cell viability in a dose and time dependent manner. Loss of viability in pyridoxin-supplemented cells is probably related to less cell cycle progression, higher active caspase 3 expression and apoptosis. In addition, Bcl-2 expression did not appear to be altered by vitamin supplementation, but active caspase 3 expression was significantly increased in pyridoxine-, but not cobalamin-supplemented cells, furthermore, cobalamin inhibited the pyridoxine cytotoxicity in the cell viability assay when combined. CONCLUSION: The results suggest that pyridoxine supplementation promotes apoptosis in human glioblastoma-derived cells and may be useful to enhance the effect of cytotoxic therapies in vivo.

Survey on the Impact of COVID-19 on the Practice of Assisted Reproduction in Latin America.

OBJECTIVE: To follow the impact of the SARS-CoV-2 pandemic on the practice of assisted reproductive technology in centers reporting to the Latin American Registry during 2020. METHODS: An internally validated online survey designed on the Survey Monkey platform with a maximum of 20 closed questions was sent via e-mail or WhatsApp to the clinical director of each center reporting to the Latin American Registry of Assisted Reproduction between July and December 2020. RESULTS: The number of centers responding to the survey varied during the six months. The relative contribution of Brazil to all responses was 41.4% to 45%, followed by México (16.2% to 23.8%), Argentina (8.1% to 12.6%), Colombia (7.1% to 8.2%), Chile (3.6% to 6.1%) and Peru (4.0% to 4.9%). Most centers reported stopping activities before July 2020 (81%). COVID-19 related symptoms were a criterion on their own to postpone ovarian stimulation (80.1% to 87.7% of centers). Although in July only 76 of 166 centers (45.8%) performed embryo transfers, by October 104 of 109 centers (95.4%) performed them. In survey 6 (December), 78 of 79 centers (98.7%) that had initially closed had already reopened, although 62.3% (61 of 98 centers) still performed 80% or less of their usual number of ART cycles. CONCLUSIONS: Most centers modified their clinical practice and applied specific protocols to screen their staff and patients. Suspicion of COVID-19 delayed treatments. Despite a peak of the pandemic, by December most centers were performing all ART treatments, although the number of cycles remained low compared to pre-pandemic numbers.

Tratamiento del embarazo ectópico implantado en cicatriz de cesárea: estudio de cohorte 2018-2022, Lima, Perú / Treatment of ectopic pregnancy implanted on cesarean scar: cohort study 2018-2022, Lima, Peru

Objetivos: Describir las características clínicas y el tratamiento del embarazo ectópico implantado en la cicatriz de cesárea, así como las complicaciones y el pronóstico obstétrico. Materiales y métodos: Estudio de cohorte retrospectivo de gestantes con diagnóstico de embarazo ectópico implantado en la cicatriz de cesárea según los criterios de la Sociedad de Medicina Materno-Fetal, atendidas entre enero de 2018 y marzo de 2022 en dos instituciones de alta complejidad, pertenecientes a la seguridad social, ubicadas en Lima, Perú. Se hizo un muestreo consecutivo. Se midieron variables sociodemográficas y clínicas de ingreso, diagnóstico, tipo de tratamiento, complicaciones y pronóstico obstétrico. Se hace un análisis descriptivo. Resultados: Se incluyeron 17 pacientes, de 29.919 partos. De estas, el 41,2 % recibió tratamiento médico y el resto recibió tratamiento quirúrgico. Se realizó un manejo local exitoso con metotrexato en el saco gestacional en dos pacientes con ectópico tipo 2. Cuatro de las pacientes requirieron histerectomía total. Seis pacientes experimentaron una gestación después del tratamiento, y 4 de ellas culminaron el embarazo con una madre y un neonato saludables. Conclusiones: El embarazo ectópico implantado en la cicatriz de una cesárea es una entidad poco frecuente, para la cual se cuenta con alternativas de manejo médico y quirúrgico con aparentes buenos resultados. Se requieren más estudios con mayor calidad metodológica de asignación aleatoria que ayuden a caracterizar la seguridad y la efectividad de las diferentes alternativas terapéuticas para las mujeres con sospecha de esta patología.

Objectives: To describe the clinical characteristics and treatment of ectopic pregnancy arising in the cesarean section scar, as well as its complications and obstetric prognosis. Material and methods: Retrospective cohort study of pregnant women with the diagnosis of a scar pregnancy in accordance with Maternal-Fetal Medicine Society criteria, seen between January 2018 and March 2022 in two high complexity institutions of the social security system, located in Lima, Peru. Consecutive sampling was used. Baseline sociodemographic and clinical variables were measured, including diagnosis, type of treatment, complications and obstetric prognosis. A descriptive analysis was performed. Results: Out of 29,919 deliveries, 17 patients were included. Of these, 41.2 % received medical management and the rest were treated surgically. Successful management with intra-gestational sac methotrexate was performed in two patients with ectopic pregnancy type 2. Four patients required total hysterectomy. Six patients became pregnant after the treatment and 4 completed their pregnancy with healthy mother and neonate pairs. Conclusions: Ectopic pregnancy implanted in a cesarean section scar is an infrequent occurrence for which medical and surgical management options are available with apparently good outcomes. Further studies of better methodological quality and random assignment are needed in order to help characterize the safety and effectiveness of the various therapeutic options for women with suspected scar pregnancy.

Treatment of ectopic pregnancy implanted on cesarea scar: cohort study 2018-2022, Lima, Peru / Tratamiento del embarazo ectópico implantado en cicatriz de cesárea: estudio de cohorte 2018-2022, Lima, Perú

Objectives: To describe the clinical characteristics and treatment of ectopic pregnancy arising in the cesarean section scar, as well as its complications and obstetric prognosis. Material and methods: Retrospective cohort study of pregnant women with the diagnosis of a scar pregnancy in accordance with Maternal-Fetal Medicine Society criteria, seen between January 2018 and March 2022 in two high complexity institutions of the social security system, located in Lima, Peru. Consecutive sampling was used. Baseline sociodemographic and clinical variables were measured, including diagnosis, type of treatment, complications and obstetric prognosis. A descriptive analysis was performed. Results: Out of 29,919 deliveries, 17 patients were included. Of these, 41.2 % received medical management and the rest were treated surgically. Successful management with intra-gestational sac methotrexate was performed in two patients with ectopic pregnancy type 2. Four patients required total hysterectomy. Six patients became pregnant after the treatment and 4 completed their pregnancy with healthy mother and neonate pairs. Conclusions: Ectopic pregnancy implanted in a cesarean section scar is an infrequent occurrence for which medical and surgical management options are available with apparently good outcomes. Further studies of better methodological quality and random assignment are needed in order to help characterize the safety and effectiveness of the various therapeutic options for women with suspected scar pregnancy.

Objetivos: describir las características clínicas y el tratamiento del embarazo ectópico implantado en la cicatriz de cesárea, así como las complicaciones y el pronóstico obstétrico. Materiales y métodos: estudio de cohorte retrospectivo de gestantes con diagnóstico de embarazo ectópico implantado en la cicatriz de cesárea según los criterios de la Sociedad de Medicina Materno-Fetal, atendidas entre enero de 2018 y marzo de 2022 en dos instituciones de alta complejidad, pertenecientes a la seguridad social, ubicadas en Lima, Perú. Se hizo un muestreo consecutivo. Se midieron variables sociodemográficas y clínicas de ingreso, diagnóstico, tipo de tratamiento, complicaciones y pronóstico obstétrico. Se hace un análisis descriptivo. Resultados: se incluyeron 17 pacientes, de 29.919 partos. De estas, el 41,2 % recibió tratamiento médico y el resto recibió tratamiento quirúrgico. Se realizó un manejo local exitoso con metotrexato en el saco gestacional en dos pacientes con ectópico tipo 2. Cuatro de las pacientes requirieron histerectomía total. Seis pacientes experimentaron una gestación después del tratamiento, y 4 de ellas culminaron el embarazo con una madre y un neonato saludables. Conclusiones: el embarazo ectópico implantado en la cicatriz de una cesárea es una entidad poco frecuente, para la cual se cuenta con alternativas de manejo médico y quirúrgico con aparentes buenos resultados. Se requieren más estudios con mayor calidad metodológica de asignación aleatoria que ayuden a caracterizar la seguridad y la efectividad de las diferentes alternativas terapéuticas para las mujeres con sospecha de esta patología.

Laccase-luminol chemiluminescence system: an investigation of substrate inhibition.

Chemiluminescence (CL) reactions are widely used for the detection and quantification of many types of analytes. Laccase has previously been proposed in CL reactions; however, its light emission behaviour has not been characterized. This study was conducted to characterize the laccase-luminol system, determine its kinetic parameters, and analyze the effects of protein and OH- concentration on the CL signal. Laccase from Coriolopsis gallica was combined with different concentrations of luminol (125 nM to 4 mM), and the enzyme kinetics were evaluated using diverse kinetic models. The laccase-luminol system was able to produce CL without an intermediate molecule, but it exhibited substrate-inhibition behaviour. A two-site random model was used and suggested that when the first luminol molecule was bound to the active site, laccase affinity for the second luminol molecule was increased. This inhibition effect could be avoided using a low luminol concentration. At 5 µM luminol concentration, 1 mg/ml (0.13 U) laccase is needed to achieve nearly 90% of the maximum CL signal, suggesting that the available luminol could not bind to all active sites. Furthermore, the concentration of NaOH negatively affected the CL signal. The laccase-luminol system represents an alternative to existing CL systems, with potential uses in molecular detection and quantification.

Engineered rHDL Nanoparticles as a Suitable Platform for Theranostic Applications.

Reconstituted high-density lipoproteins (rHDLs) can transport and specifically release drugs and imaging agents, mediated by the Scavenger Receptor Type B1 (SR-B1) present in a wide variety of tumor cells, providing convenient platforms for developing theranostic systems. Usually, phospholipids or Apo-A1 lipoproteins on the particle surfaces are the motifs used to conjugate molecules for the multifunctional purposes of the rHDL nanoparticles. Cholesterol has been less addressed as a region to bind molecules or functional groups to the rHDL surface. To maximize the efficacy and improve the radiolabeling of rHDL theranostic systems, we synthesized compounds with bifunctional agents covalently linked to cholesterol. This strategy means that the radionuclide was bound to the surface, while the therapeutic agent was encapsulated in the lipophilic core. In this research, HYNIC-S-(CH2)3-S-Cholesterol and DOTA-benzene-p-SC-NH-(CH2)2-NH-Cholesterol derivatives were synthesized to prepare nanoparticles (NPs) of HYNIC-rHDL and DOTA-rHDL, which can subsequently be linked to radionuclides for SPECT/PET imaging or targeted radiotherapy. HYNIC is used to complexing 99mTc and DOTA for labeling molecules with 111, 113mIn, 67, 68Ga, 177Lu, 161Tb, 225Ac, and 64Cu, among others. In vitro studies showed that the NPs of HYNIC-rHDL and DOTA-rHDL maintain specific recognition by SR-B1 and the ability to internalize and release, in the cytosol of cancer cells, the molecules carried in their core. The biodistribution in mice showed a similar behavior between rHDL (without surface modification) and HYNIC-rHDL, while DOTA-rHDL exhibited a different biodistribution pattern due to the significant reduction in the lipophilicity of the modified cholesterol molecule. Both systems demonstrated characteristics for the development of suitable theranostic platforms for personalized cancer treatment.

Population attitude and access to the healthcare system during the COVID-19 pandemic / Actitud de la población y acceso al sistema de salud durante la pandemia de COVID-19

Abstract The COVID-19 pandemic elicited important changes in community habits and behaviors, including a distancing of people from the healthcare system. The objective of this work was to understand the causes that gave rise to changes in behavior from an individual perspective in the Argentine Republic. We performed a cross-sectional, web-based survey using an online questionnaire. The survey was distributed via the WhatsApp application for smartphones among subjects across the Argentine territory using a combination of convenience and snowball sampling. We received 6176 responses. Almost 70% of respondents manifested fear of visiting a physician. One third of respondents manifested having a desire or need in at least one occasion of visiting a physician but, of these, 48% avoided it. The main reasons for avoiding visits were: 1) a recommenda tion of staying home (40%); 2) lack of access to the physician (35%); and 3) fear of contagion (26%). The most common form of consultation was through unconventional means (e-mail, telephone, or WhatsApp). One of 5 respondents had difficulties to obtain a medication prescription and 5% stopped the use of at least one medica tion. Regarding healthy habits, almost 2/3 of those surveyed stated that they became more sedentary; 11% of hypertensive patients increased their consumption of salt and 15% saw their blood pressure values increase, while 16% of dyslipidemic patients showed increased consumption of fats.

Resumen La pandemia de COVID-19 determinó un importante cambio de los hábitos y comportamientos comu nitarios, entre ellos se observó un distanciamiento de la gente del sistema de salud y el abandono de hábitos saludables. El objetivo de este trabajo fue comprender las causas que dieron lugar a dichos cambios de com portamiento desde una perspectiva individual y evaluar el impacto en el control de los factores de riesgo car diovasculares. Realizamos una encuesta utilizando un cuestionario en línea y distribuida mediante la aplicación WhatsApp entre personas de la Argentina utilizando una combinación de muestreo por conveniencia y en "bola de nieve". Recibimos 6176 respuestas, casi el 70% de los encuestados manifestaron temor de realizar una con sulta médica. Un tercio de los encuestados manifestó haber tenido necesidad de ir al médico en al menos una oportunidad desde el inicio de la pandemia, pero de éstos, el 48% evitó la visita. Las principales razones para evitarla: 1) la recomendación de quedarse en casa (40%); 2) dificultad para acceder al sistema de salud (35%); y 3) miedo al contagio (26%). La forma de consulta más común fue a través de medios no convencionales (correo electrónico, teléfono o WhatsApp). Uno de cada 5 encuestados tuvo dificultades para obtener una receta y el 5% dejó de tomar al menos un medicamento. En cuanto a los hábitos saludables, casi 2/3 de los encuestados afirmaron volverse más sedentarios, el 11% de los hipertensos aumentó su consumo de sal y el 15% aumentó sus valores de presión arterial, mientras que el 16% de los dislipidémicos mostró un mayor consumo de grasas.

Population attitude and access to the healthcare system during the COVID-19 pandemic.

The COVID-19 pandemic elicited important changes in community habits and behaviors, including a distancing of people from the healthcare system. The objective of this work was to understand the causes that gave rise to changes in behavior from an individual perspective in the Argentine Republic. We performed a cross-sectional, web-based survey using an online questionnaire. The survey was distributed via the WhatsApp application for smartphones among subjects across the Argentine territory using a combination of convenience and snowball sampling. We received 6176 responses. Almost 70% of respondents manifested fear of visiting a physician. One third of respondents manifested having a desire or need in at least one occasion of visiting a physician but, of these, 48% avoided it. The main reasons for avoiding visits were: 1) a recommendation of staying home (40%); 2) lack of access to the physician (35%); and 3) fear of contagion (26%). The most common form of consultation was through unconventional means (e-mail, telephone, or WhatsApp). One of 5 respondents had difficulties to obtain a medication prescription and 5% stopped the use of at least one medication. Regarding healthy habits, almost 2/3 of those surveyed stated that they became more sedentary; 11% of hypertensive patients increased their consumption of salt and 15% saw their blood pressure values increase, while 16% of dyslipidemic patients showed increased consumption of fats.

La pandemia de COVID-19 determinó un importante cambio de los hábitos y comportamientos comunitarios, entre ellos se observó un distanciamiento de la gente del sistema de salud y el abandono de hábitos saludables. El objetivo de este trabajo fue comprender las causas que dieron lugar a dichos cambios de comportamiento desde una perspectiva individual y evaluar el impacto en el control de los factores de riesgo cardiovasculares. Realizamos una encuesta utilizando un cuestionario en línea y distribuida mediante la aplicación WhatsApp entre personas de la Argentina utilizando una combinación de muestreo por conveniencia y en "bola de nieve". Recibimos 6176 respuestas, casi el 70% de los encuestados manifestaron temor de realizar una consulta médica. Un tercio de los encuestados manifestó haber tenido necesidad de ir al médico en al menos una oportunidad desde el inicio de la pandemia, pero de éstos, el 48% evitó la visita. Las principales razones para evitarla: 1) la recomendación de quedarse en casa (40%); 2) difi cultad para acceder al sistema de salud (35%); y 3) miedo al contagio (26%). La forma de consulta más común fue a través de medios no convencionales (correo electrónico, teléfono o WhatsApp). Uno de cada 5 encuestados tuvo dificultades para obtener una receta y el 5% dejó de tomar al menos un medicamento. En cuanto a los hábitos saludables, casi 2/3 de los encuestados afirmaron volverse más sedentarios, el 11% de los hipertensos aumentó su consumo de sal y el 15% aumentó sus valores de presión arterial, mientras que el 16% de los dislipidémicos mostró un mayor consumo de grasas.

Intubación endotraqueal intraparto en fetos con obstrucción de la vía aérea. Dos primeros casos de cirugía EXIT en el Hospital Rebagliati - EsSalud

Se presenta dos casos de gestantes en el tercer trimestre de gestación referidas para manejo de tumor cervical fetal con obstrucción de la vía respiratoria. Los casos fueron programados para cirugía fetal EXIT (ex-utero intrapartum treatment) que permitió la intubación orotraqueal intraparto controlada evitando el período de hipoxia y potencial asfixia que ocurrirían con el procedimiento neonatal convencional. Los recién nacidos fueron operados posteriormente por los cirujanos de cirugía de cabeza y cuello para la reducción de la masa cervical. Se sugiere plantear este procedimiento en los casos en que se sospeche obstrucción severa de la vía aérea y referirlos a centros que cuenten con una unidad de cirugía fetal con equipo médico multidisciplinario.

Two cases of pregnant women in the third trimester of gestation referred for management of fetal cervical tumor with airway obstruction are presented. The cases were scheduled for EXIT (ex-utero intrapartum treatment), fetal surgery which allowed controlled intrapartum orotracheal intubation avoiding the period of hypoxia and potential asphyxia that would occur with the conventional neonatal procedure. The neonates were subsequently operated on by head and neck surgeons for reduction of the cervical mass. It is suggested to consider this procedure in cases where severe airway obstruction is suspected and to refer them to centers that have a fetal surgery unit with a multidisciplinary medical team.

Anastomosis placentarias en embarazos gemelares monocoriales: estudio mediante técnicas de inyección vascular y relación con complicaciones fetales / Placental anastomoses in monochorionic twin pregnancies: study using vascular injection techniques and relationship with fetal complications

RESUMEN Introducción. Los embarazos gemelares son clasificados en dos grupos: monocoriónico (MC) y dicoriónico (DC). Los gemelos MC tienen 5 a 6 veces más riesgo de tener un resultado perinatal adverso. Se publica el estudio de un grupo de 22 placentas de pacientes con embarazo gemelar monocoriónico que presentaron complicaciones como síndrome de transfusión feto-fetal (STFF), secuencia de anemia policitemia (TAPS), perfusión arterial reversa (TRAP) y restricción de crecimiento intrauterino selectivo (RCIU-s). Objetivo . Determinar los tipos de anastomosis predominantes en las placentas con síndrome de transfusión feto-fetal, secuencia de anemia policitemia, síndrome de perfusión arterial reversa y restricción de crecimiento selectivo. Metodología . Se aplicó la técnica de inyección vascular placentaria para el reconocimiento de las anastomosis. Resultados . El número medio de anastomosis por placenta en el STFF (que fue la complicación más severa) fue de 8,2 ± 2,2. Las anastomosis AV y VA predominaron en un 83%. Hubo signos de discordancia placentaria en 30% de las placentas, y un 40% de placentas presentaron cordón de inserción velamentosa. Conclusiones. Las anastomosis vasculares no solo están implicadas en la etiología de las principales patologías propias de gestaciones monocoriónicas, sino que también influyen en su manejo. Creemos que un adecuado estudio placentario de cada uno de estos casos mediante la técnica de inyección vascular placentaria sería indispensable en los centros que aspiran a desarrollar manejos diferenciados de terapia fetal para cada una de estas complicaciones.

ABSTRACT Introduction: Twin pregnancies are classified into two groups: monochorionic (MC) and dichorionic (DC). MC twins are 5 to 6 times more likely to have an adverse perinatal outcome. The study of a group of 22 placentas from patients with monochorionic twin pregnancy who presented with complications such as feto-fetal transfusion syndrome (FFTS), twin anemia polycythemia sequence (TAPS), twin reverse arterial perfusion syndrome (TRAP) and selective intrauterine growth restriction (sIUGR) is presented. Objective: To determine the predominant types of anastomoses in placentas with feto-fetal transfusion syndrome, twin anemia polycythemia sequence, reverse arterial perfusion syndrome and selective intrauterine growth restriction. Methodology: The placental injection technique was applied for the recognition of anastomoses. Results: The mean number of anastomoses per placenta in STFF, which was the most severe complication, was 8.2 ± 2.2. The AV and VA anastomoses predominated in 83%. There were signs of placental discordance in 30% of placentas, and 40% of placentas presented velamentous cord insertion. Conclusions: Vascular anastomoses are not only involved in the etiology of the main pathologies of monochorionic gestations, but also influence their management. We believe that an adequate placental study of each of these cases by means of the placental vascular injection technique would be essential in centers that aspire to develop differentiated fetal management for each of these complications.

Targeted photodynamic therapy using reconstituted high-density lipoproteins as rhodamine transporters.

Reconstituted high-density lipoprotein (rHDL) nanoparticles are excellent transporters of molecules and very useful for targeted therapy as they specifically recognize the scavenger receptor, class B1 (SR-B1) that is present on the surface of a wide range of tumor cells. However, they have rarely been employed to transport photosensitizers (PS) for photodynamic therapy (PDT). Rhodamine (R) compounds have been dismissed as useful PSs for PDT due to their low 1O2 production, excitation wavelengths with little tissue penetration, and poor selectivity for tumor cells. It was recently demonstrated that when irradiating at 532 nm or with Cerenkov radiation (CR) from a ß-emitting radionuclide, R123, R6G, and RB undergo electron transfer reactions (type I reaction) with folic acid. R6G also produces type I reactions with O2. In this work, the photodynamic effects of the rHDL-R system were evaluated in vitro. rHDL nanoparticles loaded with R123, R6G, and RB were synthesized, and the PS was internalized into T47D tumor cells. When cells were irradiated with a 532-nm laser in the presence of an rHDL-R systems, a cytotoxic photodynamic effect was obtained in the order R6G > R123 > RB. In the presence of CR from a 177Lu source, cytotoxicity showed the order R6G > RB > R123. The higher cytotoxicity induced by R6G in both cases corresponds to higher cellular internalization and larger production of type I and II reactions. Thus, in this work, it is proposed that rHDL-R/177Lu system can be applied in theragnostics as a multimodal radiotherapy-PDT-imaging system (imaging by SPECT or Cerenkov) and in hypoxic solid tumors in which external radiation is not effective and 177Lu-CR acts as light source.

A Multimodal Theranostic System Prepared from High-Density Lipoprotein Carrier of Doxorubicin and 177Lu.

Recently, it was demonstrated that doxorubicin (Dox.HCl), a chemotherapeutic agent, could be photoactivated by Cerenkov radiation (CR). The objective of the present work was to develop a multimodal chemotherapy-radiotherapy-photodynamic therapeutic system based on reconstituted high-density lipoprotein (rHDL) loaded with Dox.HCl and 177Lu-DOTA. 177Lu acts as a therapeutic radionuclide and CR source. The system can be visualized by nuclear imaging. Fluorescence microscopy showed that rHDL-Dox specifically recognized cancer cells (T47D) that are positive for SR-B1 receptors. Encapsulated Dox.HCl was released into the cells and produced reactive oxygen species when irradiated with a 450-nm laser (photodynamic effect). The same effect occurred when Dox.HCl was irradiated by 177Lu CR. Through in vitro experiments, it was confirmed that the addition of 177Lu-DOTA to the rHDL-Dox nanosystem did not affect the specific recognition of SR-B1 receptors expressed in cells, or the cellular internalization of 177Lu-DOTA. The toxicity induced by the rHDL-Dox/177Lu nanosystem in cell lines with high (T47D and PC3), poor (H9C2) and almost-zero (human fibroblasts (FB)) expression of SR-B1 was evaluated in vitro and confirmed the synergy of the combined chemotherapy-radiotherapy-photodynamic therapeutic effect; this induced toxicity was proportional to the expression of the SR-B1 receptor on the surface of the cells used. The HDL-Dox/177Lu nanosystem experienced uptake by tumor cells and the liver-both tissues with high expression of SR-B1 receptors-but not by the heart. 177Lu CR offered the possibility of imparting photodynamic therapy where laser light could not reach.

RACCOVID-19: primer Registro Argentino de Complicaciones Cardiovasculares en pacientes con COVID-19 / RACCOVID-19: First Argentine Registry of Cardiovascular Complications in COVID-19 Patients

RESUMEN Introducción: La enfermedad por coronavirus (COVID-19) ha causado una de las mayores pandemias conocidas al día de la fecha. La Sociedad Argentina de Cardiología (SAC) y la Federación Argentina de Cardiología (FAC) elaboraron el primer Registro Argentino de Complicaciones Cardiovasculares en pacientes con COVID-19 (RACCOVID-19), con el propósito de relevar, a nivel nacional, su impacto en la evolución hospitalaria de estos pacientes. Objetivos: Documentar la aparición de complicaciones cardiovasculares en pacientes internados por COVID-19 y evaluar predictores de riesgo de dichas complicaciones y su impacto pronóstico. Material y Métodos: Se incluyen datos de 2750 pacientes en 50 centros de 11 provincias del país, desde el 18 de mayo hasta el 31 de octubre de 2020. Resultados: La edad promedio fue de 57±18 años y hubo predominio de sexo masculino (60,2%). La tasa de complicaciones cardiovasculares fue del 15,3%. La insuficiencia cardíaca (43,5%), las arritmias (33,5%) y el daño miocárdico (31,1%) fueron las complicaciones más frecuentes. La mortalidad fue del 19,3%. Un modelo de predicción de sobrevida en la etapa hospitalaria incluyó las siguientes variables: edad, sexo masculino, valores de hematocrito y creatinina al ingreso, existencia de antecedentes patológicos, formas de presentación de COVID-19 graves y presencia de complicaciones cardiovasculares. Conclusiones: El registro RACCOVID-19 mostró una tasa de complicaciones cardiovasculares del 15,3%. La mortalidad total del registro fue del 19,3% y las complicaciones cardiovasculares junto con otras variables de presentación, así como la gravedad del cuadro clínico de COVID-19, forman parte de un perfil de riesgo clínico asociado a mayor mortalidad.

ABSTRACT Background: Coronavirus disease (COVID-19) has caused one of the largest pandemics known to date. The Argentine Society of Cardiology (SAC) and the Argentine Federation of Cardiology (FAC) have developed the First Argentine Registry of Cardiovascular Complications in COVID-19 patients (RACCOVID-19) with the purpose of performing a nationwide review of their impact in the in-hospital evolution of these patients. Objectives: The aim of this study was to record cardiovascular complications in hospitalized patients for COVID-19, and to evaluate risk predictors of these complications and their prognostic impact. Methods: A total of 2750 patients from 50 centers in 11 provinces of the country were included from May 18 to October 31, 2020. Results: Mean age was 57±18 years, with a prevalence of male gender (60.2%). Cardiovascular complications occurred in 15.3% of cases. Heart failure (43.5%), arrhythmias (33.5%) and myocardial injury (31.1%) were the most relevant complications. Mortality was 19.3%, and a predictive model of in-hospital survival included age, male gender, admission hematocrit and creatinine, history of previous diseases, severe forms of COVID-19 presentation and cardiovascular complications. Conclusions: The RACCOVID-19 registry showed 15.3% of cardiovascular complications. Overall mortality was 19.3% and cardiovascular complications together with other presentation variables as well as the clinical severity of COVID-19, are part of a clinical risk profile associated with higher mortality.

Discontinuación de la anticoagulación y sus factores asociados en la fibrilación auricular / Discontinuation of Anticoagulation and Associated Factors in Atrial Fibrillation

RESUMEN Introducción: El objetivo del estudio fue comparar si existe diferencia en la discontinuación de los antagonistas de la vitamina K y los anticoagulantes directos y evaluar sus factores asociados en la fibrilación auricular de reciente diagnóstico. Material y métodos: Se realizó un estudio de cohortes prospectivo. El período de seguimiento fue de 12 meses. Debido a que la asignación del tratamiento no fue al azar, se realizó una ponderación por puntaje de propensión considerando las características basales potencialmente asociadas a la exposición y al resultado. Se evaluaron factores asociados a la discontinuación del anticoagulante mediante un modelo de Cox ponderado. Se incluyeron 379 pacientes con una edad media de 78 años (DE ± 9) y una prevalencia de sexo femenino del 58%. La mediana de seguimiento fue de 362 días (rango intercuartilo: 347-370 días). La pérdida de seguimiento fue del 1%. Resultados: El modelo de tiempo a la discontinuación del tratamiento anticoagulante ponderado evidenció un HR crudo de 1,40 (IC 95%: 0,79-2,48) y uno ajustado por edad, tipo de fibrilación auricular, ablación por radiofrecuencia, sangrado, cantidad de fármacos crónicos y de consultas médicas durante el seguimiento de 1,26 (IC 95%: 0,75-2,12) para el grupo tratado con anticoagulantes directos en comparación con el tratado con antagonistas de la vitamina K. Conclusiones: En nuestro medio, la discontinuación de los anticoagulantes en la fibrilación auricular no se asociaría con el tipo de fármaco empleado, la edad o el tipo de arritmia. La ablación por radiofrecuencia, la ocurrencia de sangrado y el número de consultas médicas se asociaron con la discontinuación.

ABSTRACT Background: The aim of the study was to compare if there were any differences between discontinuation of vitamin K antagonists and direct oral anticoagulants and evaluate the factors associated with such discontinuation in newly diagnosed nonvalvular atrial fibrillation. Methods: We conducted a prospective cohort study. Patients were followed-up for 12 months. Since the assignment of anticoagulation treatment was not randomized, propensity score weighting was used considering the baseline characteristics potentially associated with the exposure and result. Factors associated with the discontinuation of anticoagulant treatment were analyzed with a weighted Cox proportional hazards model. A total of 379 patients were included; mean age was 78 years (SD ± 9) and 58% were women. Median follow-up was 362 days (interquartile range: 347-370 days) and 1% was lost to follow-up. Results: The model of time to discontinuation based on inverse probability treatment weighting showed a crude HR of 1.40 (95% CI, 0.79-2.48, and of 1.26 (95% CI, 0.75-2,12, after adjustment for age, type of atrial fibrillation, radiofrequency catheter ablation, bleeding, number of chronic medications and number of medical visits during follow-up for the group treated with direct oral anticoagulants compared with the vitamin K antagonists. Conclusions: In our setting, anticoagulant discontinuation in nonvalvular atrial fibrillation would not be associated with the type of drug used, age or type of atrial fibrillation. Radiofrequency catheter ablation, bleeding events and the number of medical visits were associated with treatment discontinuation.

Complexity Analysis of the Default Mode Network Using Resting-State fMRI in Down Syndrome: Relationships Highlighted by a Neuropsychological Assessment.

BACKGROUND: Studies on complexity indicators in the field of functional connectivity derived from resting-state fMRI (rs-fMRI) in Down syndrome (DS) samples and their possible relationship with cognitive functioning variables are rare. We analyze how some complexity indicators estimated in the subareas that constitute the default mode network (DMN) might be predictors of the neuropsychological outcomes evaluating Intelligence Quotient (IQ) and cognitive performance in persons with DS. METHODS: Twenty-two DS people were assessed with the Kaufman Brief Test of Intelligence (KBIT) and Frontal Assessment Battery (FAB) tests, and fMRI signals were recorded in a resting state over a six-minute period. In addition, 22 controls, matched by age and sex, were evaluated with the same rs-fMRI procedure. RESULTS: There was a significant difference in complexity indicators between groups: the control group showed less complexity than the DS group. Moreover, the DS group showed more variance in the complexity indicator distributions than the control group. In the DS group, significant and negative relationships were found between some of the complexity indicators in some of the DMN networks and the cognitive performance scores. CONCLUSIONS: The DS group is characterized by more complex DMN networks and exhibits an inverse relationship between complexity and cognitive performance based on the negative parameter estimates.

Classical and Quantum H-Theorem Revisited: Variational Entropy and Relaxation Processes.

We propose a novel framework to describe the time-evolution of dilute classical and quantum gases, initially out of equilibrium and with spatial inhomogeneities, towards equilibrium. Briefly, we divide the system into small cells and consider the local equilibrium hypothesis. We subsequently define a global functional that is the sum of cell H-functionals. Each cell functional recovers the corresponding Maxwell-Boltzmann, Fermi-Dirac, or Bose-Einstein distribution function, depending on the classical or quantum nature of the gas. The time-evolution of the system is described by the relationship dH/dt≤0, and the equality condition occurs if the system is in the equilibrium state. Via the variational method, proof of the previous relationship, which might be an extension of the H-theorem for inhomogeneous systems, is presented for both classical and quantum gases. Furthermore, the H-functionals are in agreement with the correspondence principle. We discuss how the H-functionals can be identified with the system's entropy and analyze the relaxation processes of out-of-equilibrium systems.

Asociación entre sentido de coherencia y control glucémico en personas con Diabetes Mellitus tipo 2 / Associação entre Senso de Coerência e controle glicêmico em pessoas com Diabetes Mellitus Tipo 2 / Association between Sense of Coherence and glycemic control in people with Type 2 Mellitus Diabetes

Objetivo: Evaluar la asociación entre sentido de coherencia y control glucémico en adultos con Diabetes Mellitus tipo 2. Métodos: Estudio de tipo transversal desarrollado durante el año 2018 en el cual fueron encuestados 220 diabéticos de tres unidades de Salud de la Secretaría de Salud del Estado de Jalisco en Ciudad Guzmán, México. Se les aplicó el instrumento SOC-13 para sentido de coherencia y el control glucémico se evaluó por medio del nivel de hemoglobina glucosilada que se obtuvo del expediente médico. Los datos se analizaron por medio del análisis de regresión logística. Resultados: Se obtuvieron resultados con un total de 220 participantes en un rango de edad entre 23 y 69 años de los que el 67% presentó control glucémico inadecuado y el 33% control glucémico adecuado; de los encuestados con control glucémico inadecuado el 24% refirió puntuaciones bajas de sentido de coherencia, mientras que el 96% de quienes tienen control glucémico adecuado obtuvo puntuaciones medio/alta de sentido de coherencia. Los análisis de regresión logística arrojan que el sentido de coherencia se asocia significativamente con el control glucémico (OR = 7.2; 95% C.I: 2.0-24.7; p = 0.002) después de ajustar los análisis por diversas variables confusoras como sexo, apego al plan alimenticio, actividad física, ausencia de complicaciones y ausencia de tabaquismo. Conclusión: Los diabéticos con puntuaciones medio/altas de sentido de coherencia tienen hasta 7 veces más probabilidad de tener control glucémico adecuado que diabéticos con puntuaciones bajas de sentido de coherencia independientemente de variables intervinientes.

Objetivo: Avaliar a associação entre senso de coerência e controle glicêmico em adultos com diabetes mellitus tipo 2. Métodos: Estudo transversal desenvolvido durante 2018, com 220 diabéticos de três unidades de saúde da Secretaria de Saúde do Estado de Jalisco na cidade de Guzmán, México. Aplicou-se o instrumento SOC-13 para senso de coerência, e avaliou-se o controle glicêmico por meio do nível de hemoglobina glicosada obtido nos prontuários. Assim, obtiveram-se os dados por análise de regressão logística. Resultados: Os 220 participantes tinham faixa etária de 23 a 69 anos, dos quais 148 (67%) apresentavam controle glicêmico inadequado e 72 (33%) controle glicêmico adequado; 24% dos pesquisados com controle glicêmico inadequado relataram escores baixos para senso de coerência, enquanto 96% daqueles com controle glicêmico adequado obtiveram escores médios/ altos para senso de coerência. As análises de regressão logística mostram que o senso de coerência está significativamente associado ao controle glicêmico (OR=7,2; IC 95%: 2,0-24,7; p=0,002) após ajustar as análises para variáveis de confusão, como sexo, adesão ao plano alimentar, atividade física, ausência de complicações e ausência de tabagismo. Conclusão: Diabéticos, com escores médios/altos de senso de coerência, têm até 7 vezes mais chances de apresentar controle glicêmico adequado do que diabéticos com baixos escores de senso de coerência, independentemente das variáveis intervenientes.

Objective: To evaluate the association between a sense of coherence and glycemic control in adults with type 2 Mellitus Diabetes. Methods: Cross-sectional study, developed during 2018, 220 diabetics from three health units of the Secretaria de Salud del Estado de Jalisco in Ciudad Guzmán, Mexico, the SOC-13 instrument was applied for a sense of coherence, glycemic control was evaluated through the level of glycosylated hemoglobin obtained from the medical record, the data was analyzed through logistic regression analysis. Results: Results were obtained with a total of 220 participants in an age range of 23 to 69 years of which 67% presented inadequate glycemic control and 33% adequate glycemic control; 24% of those surveyed with inadequate glycemic control reported low scores for a sense of coherence, while 96% of those with adequate glycemic control obtained medium/high scores for a sense of coherence. The logistic regression analyzes show that the sense of coherence is significantly associated with glycemic control (OR=7.2; 95% CI: 2.0-24.7; p=0.002) after adjusting the analyzes for various confounding variables such as sex, adherence to eating plan, physical activity, absence of complications and absence of smoking. Conclusion: Diabetics with medium/high scores of coherence sense are up to 7 times more likely to have adequate glycemic control than diabetics with low scores of coherence sense regardless of intervening variables.

Embarazo ectópico abdominal: reporte de dos casos / Abdominal ectopic pregnancy: Report of two cases / Abdominal ectopic pregnancy: Report of two cases

RESUMEN Presentamos dos casos de embarazo ectópico abdominal de 16 y 26 semanas, evaluados con ecografía y resonancia magnética. Ambos casos ingresaron con cuadro de abdomen agudo quirúrgico, el de mayor edad gestacional con descompensación hemodinámica por hemoperitoneo secundario a desprendimiento placentario. La presentación clínica conllevó a la resolución por laparotomía y extracción del feto y del tejido placentario, terminando el primer caso en histerectomía por compromiso trofoblástico de la superficie uterina y órganos adyacentes. El neonato de 26 semanas falleció luego de 4 meses, por sepsis tardía. La sospecha clínica por amenorrea y dolor abdominal intenso son criterios importantes, y los estudios de imágenes, especialmente la ecografía transvaginal y pélvica, son las principales herramientas diagnósticas.

ABSTRACT We present two cases of abdominal ectopic pregnancy of 16 and 26 weeks, evaluated with ultrasound and magnetic resonance imaging. Both cases presented an acute surgical abdomen, the case with the oldest gestational age showed hemodynamic decompensation due to hemoperitoneum secondary to placental abruption. The clinical presentation led to resolution by laparotomy and extraction of the fetus and placental tissue, ending in hysterectomy due to trophoblastic involvement of the uterine surface and adjacent organs in the first case. The 26-week-neonate died after 4 months due to late sepsis. Clinical suspicion for amenorrhea and severe abdominal pain are important criteria, and imaging studies, especially ultrasound, are the main diagnostic tools.