Acetylated galactopyranosyl N-heterocyclic monocarbene complexes of Silver(I) as novel anti-proliferative agents in a rhabdomyosarcoma cell line.

Herein, four silver(I) complexes bearing acetylated d-galactopyranoside-based N-heterocyclic carbene ligands were synthesized and fully characterized by elemental analysis, NMR, and X-ray photoelectron spectroscopy. All complexes were obtained with an anomeric ß-configuration and as monocarbene species. In this study, we investigated the biological effects of the silver(I) complexes 2a-d on the human rhabdomyosarcoma cell line, RD. Our results show concentration-dependent effects on cell density, growth inhibition, and activation of key signaling pathways such as Akt 1/2, ERK 1/2, and p38-MAPK, indicating their potential as anticancer agents. Notably, at 35.5 µM, the complexes induced mitochondrial network disruption, as observed with 2b and 2c, whereas with 2a, this disruption was accompanied by nuclear content release. These results provide insight into the utility of carbohydrate incorporated NHC complexes of silver(I) as new agents in cancer therapy.

Development of new 1, 3-dihydroxyacridone derivatives as Akt pathway inhibitors in skeletal muscle cells.

In the present work, four new compounds based on the privileged structure acridone were efficiently synthesized following simple operational techniques and biologically tested on proliferative skeletal muscle cells (C2C12) and rhabdomyosarcoma cells (RD) showing no significant changes in the number of dead or viable cells at 1 µM during 24 or 48 h of treatment. Of relevance, acridone derivatives 3a-3d at 0.5 µM for 24 h effectively inhibited Akt activation in C2C12, while at 1 µM only compounds 3a and 3b have effect. RD cells showed a different response pattern. These cells treated with 3a (0.5 µM), 3b (0.5 µM) or 3d (0.5 or 1 µM) for 24 h shown significant Akt inhibition. In addition, 3a-3d assayed at 1 µM for 48 h were highly successful in inhibiting Akt phosphorylation. Finally, based on molecular docking and molecular dynamics simulations, we rationalize the experimental results mentioned above and propose that 3-phosphoinositide-dependent kinase-1 (PDK1) could be one of the molecular targets of this new series of 1, 3-dihydroxyacridone derivatives. Biological and in silico studies revealed that 3b could be considered as the most promising prototype for the development of new antitumor agents.

Effects of calcitriol on the cell cycle of rhabdomyosarcoma cells.

Rhabdomyosarcoma (RMS) is a type of cancer of skeletal muscle. Calcitriol is the active form of vitamin D3, also recognised as a steroid hormone called 1α, 25-dihydroxy vitamin D3 (1,25D). We previously reported that 1,25D promoted cell proliferation and differentiation in non-cancerous skeletal muscle cells C2C12. The aim of this work is to evaluate some of the events triggered by 1,25D in RD cells, a human RMS cell line. In this work we reported that RD cells expressed vitamin D receptor (VDR) and treatment with 1,25D reduced VDR expression at 72 h. At the same time an acute decrease in viable cells as well as in cells in S-phase of cell cycle was also observed. Furthermore, up-regulation of p15INK4b was accompanied in a timely manner by down-regulation of cyclin D3, p21Waf1/Cip1 and myogenin protein levels. Simultaneously, 1,25D induced early apoptosis markers such as cyclin D1 and CDK4, and the disruption of the mitochondrial network together with a redistribution of mitochondria around the nucleus. Finally, 1,25D induced changes in the plasma membrane of RD cells associated with early and late apoptosis at 72 h, as determined by flow cytometry. Taken together, these results determine that treatment with 1,25D for 72 h triggers apoptosis in RD cells.

El contacto piel a piel como promotor de la lactancia materna, y su posible relación con la disminución de la hiperbilirrubinemia / Skin-to-skin contact as a promoter of breastfeeding, and its possible relationship with the reduction of hyperbilirubinemia

INTRODUCCIÓN: El contacto piel a piel (CPP) postparto es una práctica de atención de salud fuertemente aconsejada por la OMS, por los beneficios a largo y a corto plazo que conlleva tanto para la salud de la madre como para la del recién nacido. OBJETIVO: Realizar una búsqueda bibliográfica con el objetivo de determinar los beneficios que tiene la CPP durante el periodo del postparto inmediato sobre la lactancia materna (LM) y la ictericia neonatal (IN). RESULTADOS: Los resultados muestran que el CPP aumenta diversos indicadores de éxito de lactancia materna, dentro de los cuales destacan: aumento en la efectividad de la primera lactancia, mayor probabilidad de mantener la LM a 4 meses, aumento del periodo de LM en promedio, mayor probabilidad de LM exclusiva a 6 meses. No se encontraron mayores beneficios al iniciar el CPP antes de los 10 minutos, ni al prolongarlo más de 60 minutos. Además, el CPP indirectamente disminuye la probabilidad de presentar IN, debido a que aumenta la frecuencia de LM, indicador que se asocia de manera indirecta a los niveles de bilirrubina en el recién nacido. CONCLUSIÓN: La revisión de la literatura especializada nos permite concluir que el contacto temprano entre la madre y su hijo en sala de partos, piel a piel, tiene efectos significativamente positivos en la lactancia materna y puede llegar a representar un factor protector de la hiperbilirrubinemia no conjugada en el RN.

Postpartum skin-to-skin contact (SSC) is a health care practice strongly advised by the WHO because of the long- and short-term benefits for both maternal and newborn health. This update summarizes the main findings supporting the recommendation to perform SSC during the immediate postpartum period, specifically the benefits on breastfeeding (BF) and neonatal jaundice (NI). The results show that SSC increases several indicators of breastfeeding success, including: increased effectiveness of the first breastfeeding, greater probability of maintaining BF at 4 months, increased BF period on average, greater probability of exclusive BF at 6 months. No greater benefits were found when initiating SSC before 10 minutes, nor when prolonging it for more than 60 minutes. In addition, SSC indirectly decreases the probability of presenting NI, because it increases the frequency of BF, an indicator that is indirectly associated with bilirubin levels in the newborn. CONCLUSION: A review of the specialized literature allows us to conclude that postpartum skin-to-skin contact (SSC) has significantly positive effects on breastfeeding and may represent benefits in bilirubin levels in the newborn.

Early use of combined exogenous surfactant and inhaled nitric oxide reduces treatment failure in persistent pulmonary hypertension of the newborn: a randomized controlled trial.

OBJECTIVE: To evaluate whether combined surfactant with inhaled nitric oxide (iNO) use will prevent newborns with hypoxemic respiratory failure (HRF) from developing an Oxygenation Index (OI) > 40. METHODS: 100 term newborns with acute HRF (OI ≥ 20) were randomized to: Surfactant+iNO: received iNO plus up to two doses of surfactant or iNO-Controls: received iNO+placebo. Main outcome was the development of severe HRF (OI > 40) despite iNO use. RESULTS: Baseline mean ± SD OI was 37.4 ± 14 for the Surfactant+iNO group and 38.2 ± 16 for the controls. Infants receiving surfactant+iNO improved their oxygenation faster, resulting in lower OI at 24 h: 12.9 ± 9 vs 18.7 ± 11 of controls, p < 0.05; and a lower proportion developing OI > 40: 24%(12/50) vs 50%(25/50) of controls, p < 0.02. Fewer infants receiving surfactant+iNO presented the combined outcome of death or ECMO: 16%(8/50) compared to 36%(18/50) of controls, p < 0.05. CONCLUSIONS: Early use of combined surfactant+iNO improves oxygenation preventing the progression to severe HRF. This may reduce mortality and ECMO need. TRIAL REGISTRATION NUMBER: ISRCTN13727958.

Relationship between Assumed Differential Socialization and Emotional Disorders in Women: A Form of Covert Social Violence.

Women suffer different forms of violence, both explicit and covert, due to gender asymmetry. This study analyzes the relationship between the internalization of norms assigned to the female gender understood as a form of covert social violence and the presence of anxiety and depression. 286 women were evaluated with the Inventory of Concealed Social Violence (IVISEM) to measure the internalization of gender norms, the Inventory of Situations and Responses to Anxiety (ISRA), to measure anxiety, and the Three-Dimensional Depression Questionnaire (CTD) to measure depression. In addition, the possible influence of some variables such as maternity, age and marital status on the internalization of norms and on the presence of emotional alterations is discussed. The findings showed the relationship between IVISEM factors and the seven health indicators measured. Age appeared as a modulating variable in relation to cognitive anxiety and depression and marital status is related to all depression factors. The results show that women's internalization of gender norms can be understood as hidden social violence, since it was associated with high scores in anxiety and depression.

Relationship between assumed differential socialization and emotional disorders in women: a form of covert social violence

Women suffer different forms of violence, both explicit and covert, due to gender asymmetry. This study analyzes the relationship between the internalization of norms assigned to the female gender understood as a form of covert social violence and the presence of anxiety and depression. 286 women were evaluated with the Inventory of Concealed Social Violence (IVISEM) to measure the internalization of gender norms, the Inventory of Situations and Responses to Anxiety (ISRA), to measure anxiety, and the Three-Dimensional Depression Questionnaire (CTD) to measure depression. In addition, the possible influence of some variables such as maternity, age and marital status on the internalization of norms and on the presence of emotional alterations is discussed. The findings showed the relationship between IVISEM factors and the seven health indicators measured. Age appeared as a modulating variable in relation to cognitive anxiety and depression and marital status is related to all depression factors. The results show that women's internalization of gender norms can be understood as hidden social violence, since it was associated with high scores in anxiety and depression

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Mastectomía de Reducción de Riesgo Contralateral: impacto en la evolución de las pacientes. Experiencia del Hospital Británico de Buenos Aires / Contralateral prophylactic mastectomy: impact on the outcome of patients at the Buenos Aires British Hospital

Introducción La Mastectomía de Reducción de Riesgo Contralateral (mrrc) se ha incrementado considerablemente en los últimos años. Este aumento llama la atención debido a que la incidencia del carcinoma de mama contralateral ha disminuido gracias al diagnóstico temprano y a los avances en los tratamientos adyuvantes. No se ha podido demostrar un claro beneficio de la mrrc en la Supervivencia Global (sg), en especial en las pacientes de bajo riesgo. Objetivos Describir la evolución y las características de las pacientes con diagnóstico de cáncer de mama unilateral que optaron por realizar mrrc en el Servicio de Mastología del Hospital Británico de Buenos Aires, analizando la aparición de carcinoma contralateral, la Supervivencia Libre de Enfermedad (sle) y la Supervivencia Global (sg), y compararla con un grupo de pacientes a quienes se les realizó Mastectomía Terapéutica Unilateral (mtu). Material y método Se realizó un estudio retrospectivo de pacientes con diagnóstico de cáncer de mama unilateral tratadas con mastectomía y sometidas a mrrc entre octubre de 2005 y noviembre de 2014. Se incluyeron 46 pacientes que recibieron mrrc, y en el grupo control a 140 pacientes a las que se les realizó mtu en el mismo período de tiempo y rango etario. El seguimiento medio en el grupo de mrrc fue de 49,3 meses y en el grupo de mtu de 43,3 meses. Resultados La incidencia anual del carcinoma contralateral fue de 0,5% en nuestra casuística. Las curvas de Kaplan Meier para supervivencia libre de enfermedad y supervivencia global no muestran diferencias significativas entre ambos grupos. Tampoco se observan diferencias en los subgrupos analizados de mujeres menores de 50 años y receptores estrogénicos (re) negativos. Conclusiones No hubo beneficio en cuanto a sle y sg en las pacientes sometidas a mrrc comparadas con el grupo de mtu, aun en los subgrupos considerados de mayor riesgo como aquellas pacientes menores de 50 años y Receptores de Estrógenos (re) negativos. No hubo desarrollo de carcinomas contralaterales en el grupo de mrrc. Al ser un procedimiento solicitado por las pacientes, es importante que el cirujano cuente con la información adecuada para poder brindar la mejor recomendación para cada una de ellas

Introduction Contralateral Prophylactic Mastectomy (cpm) has considerably increased in recent years. Such increase calls our attention, since the incidence of contralateral breast carcinoma has decreased as a result of early diagnosis and of the progress made with adjuvant therapies. No clear benefit in Overall Survival (os) was proven, particularly in low risk patients. Objectives To describe the evolution and characteristics of patients with unilateral breast cancer who decided to undergo cpm at the Buenos Aires British Hospital Breast Services Unit, analyzing the appearance of contralateral carcinoma, Disease-Free Survival (dfs) and Overall Survival (os), compared to a group of patients who underwent unilateral mastectomy. Materials and method A retrospective trial was conducted on patients diagnosed with unilateral breast cancer who underwent mastectomy and cpm between October 2005 and November 2014. During the same time period and among the same age group, 46 patients received cpm and 140 patients, from the control group, underwent unilateral mastectomy. The mean follow-up period was of 49.3 months for the cpm group, and of 43.3 months for the unilateral mastectomy group. Results The annual incidence of contralateral carcinoma was 0.5% in our cases. Kaplan Meier curves for disease-free survival (dfs) and overall survival (os) show no significant differences between both groups. The same is true for subgroups of women under 50 years old with negative estrogen receptors. Conclusions There was no benefit in terms of dfs and os in patients who underwent cpm against the unilateral mastectomy group, even in subgroups considered of higher risk, such as patients under 50 and with negative er. There were no contralateral carcinomas in the cpm group. Since this procedure is requested by patients, it is important for the surgeon to have the correct information to be able to provide the best recommendation in each case

Action of Colloidal Bismuth Hydroxide Gel and its Commercial Cream on Enteropathogens and Colonizers of the Gastrointestinal Tract.

BACKGROUND: Acute diarrheal diseases constitute a world public health problem because they are the second cause of death in children under 5 years of age. Colloidal bismuth hydroxide gel (CBHG) is an active ingredient in low-cost, antidiarrhetic drugs for oral use; it does not inhibit intestinal motility, and it features very low intestinal absorption of <1%. MATERIALS AND METHODS: We analyzed the sensitivity by determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC); the effect on bacterial growth by studying the specific growth velocity and the generation time in growth curves; and bacterial attachment by counting viable plaques, of enteropathogenic Escherichia coli, shigatoxigenic E. coli O157:H7, Klebsiella pneumoniae, Salmonella spp., and Shigella flexneri in the commercial cream (Chobet® bismuth cream with pectin [CBCHP]), its active ingredient (CBHG), and its excipients (E) separately. RESULTS: CBCHP: MIC 6-10 mg/ml and MBC 7.5-15 mg/ml of bismuth; CBHG: MIC 6-10 mg/ml of bismuth. E: No inhibition was observed at the concentration studied in this study. At very low subinhibitory concentrations of CBCHP and CBHG, there was already evidence of a significant decrease in growth, which could not be recorded for E. CBCHP and CBHG presented an elevated capacity for bacterial displacement, significantly greater than E. CONCLUSIONS: We believed that the results obtained in this study are very promising from the treatment standpoint, as a possible treatment for cases of diagnosis or suspicion of bacterial gastroenteritis. The antimicrobial and attachment effects of CBCHP are exclusively due to its active ingredient CBHG; these effects are promoted in the presence of E.

Uso de palivizumab en el control de un brote de VRS en una unidad de cuidado intensivo neonatal / Use of palivizumab in the control of an outbreak of respiratory syncytial virus in a neonatal intensive care unit

El virus respiratorio sincicial (VRS) es una causa importante de morbilidad en pediatría, especialmente en los menores de 2 años. Los grupo de mayor riesgo de presentar una infección grave son los recién nacidos prematuros (RNPrT) menores de 35 semanas de edad gestacional, los pacientes portadores de enfermedad pulmonar crónica y los pacientes portadores de cardiopatías congénitas congestivas. La presencia de un brote de VRS en la unidad de cuidados intensivo neonatal (UCIN) se asocia a resultados desfavorables, incluyendo la muerte. Palivizumab es un anticuerpo monoclonal que se usa para la prevención de la infección por VRS en pacientes de riesgo durante la época epidémica estacional y cuyo uso no está formalmente indicado para el control de brotes. Se describe un brote de VRS en época epidémica en una UCIN y les medidas tomadas para su control. El uso de palivizumab asociado al uso óptimo de medidas de aislamiento para el control de infecciones virales respiratorias pareciera ser altamente efectivo en el control de un brote de VRS en la UCIN.

Respiratory syncytial virus (RSV) infection is the leading cause of morbidity in infants. High risk group presents serious infections, particularly preterm birth. An RSV outbreak occurred in the neonatal intensive care and we described the control measurements taken, including the use of palivizumab

Factores perinatales asociados a la mortalidad neonatal en recién nacidos de muy bajo peso: estudio multicéntrico / Perinatal factors associated with neonatal mortality in very low birth weight infants: A multicenter study

Introducción. Objetivos. Evaluar los factores de riesgo asociados a la mortalidad neonatal en recién nacidos de muy bajo peso (RNMBP, ≤ 1500 g) y el impacto de la administración antenatal de corticoides. Población y métodos. Análisis retrospectivo de una cohorte de RNMBP de 26 centros perinatales terciarios y universitarios de la Red Neonatal Sudamericana (NEOCOSUR), que incluye Argentina, Brasil, Chile, Paraguay, Perú y Uruguay, entre 2000 y 2011, y que cuenta con 11455 registros. Las características maternas, neonatales y la morbilidad se compararon entre los RNMBP que murieron y los sobrevivientes hasta el alta. Las variables asociadas con la muerte neonatal se determinaron mediante regresión logística. Se estimó el efecto del corticoide prenatal sobre la morbimortalidad neonatal utilizando el método de pareamiento. Resultados. La tasa de mortalidad neonatal fue de 22,3% con una elevada variabilidad entre los centros. Los factores independientemente asociados a menor mortalidad de los RNMBP fueron la administración de corticoides prenatal (OR 0,49; IC 95%: 0,43-0,54), mejor puntaje Z del peso de nacimiento (OR 0,63; 0,61-0,65), hipertensión arterial (OR 0,67; 0,58-0,77) y cesárea (OR 0,75; 0,65-0,85). Mediante pareamiento, el riesgo de muerte se redujo en 38% asociado a los corticoides prenatales. Conclusiones. Se identificaron importantes factores perinatales asociados con la mortalidad neonatal en RNMBP y se demostró el impacto de la administración de corticoides prenatales en la Red NEOCOSUR.

Introduction. Objectives. To assess risk factors associated withneonatal mortality in very low birth weight (VLBW) infants (< 1500 g) and the impact of the administration of antenatal corticosteroids. Population and methods. Retrospective analysis of a VLBW infant cohort from 26 tertiary care and teaching sites member of the South American Neonatal Network (NEOCOSUR), which includes Argentina, Brazil, Chile, Paraguay, Peru, and Uruguay, conducted between 2000 and 2011 on 11 455 records. Maternal and neonatal characteristics and morbidity were compared between deceased VLBW infants and those who survived to discharge. Outcome measures associated with neonatal mortality were established by logistic regression. The effect of antenatal corticosteroids on neonatal morbidity and mortality was estimated using the matching method. Results. The neonatal mortality rate was 22.3%, and variability among sites was elevated. Factors that were independently associated with a lower mortality of VLBW infants included the administration of antenatal corticosteroids (OR: 0.49, 95% CI: 0.43-0.54), a better birth weight Z-score (OR: 0.63, 0.61-0.65), arterial hypertension (OR: 0.67, 0.58-0.77), and C-section (OR: 0.75, 0.65-0.85). The matching method allowed reducing the risk of death by 38% in association with antenatal corticosteroids. Conclusions. Major perinatal factors were identified in association with neonatal mortality in VLBW infants, and the impact of antenatal corticosteroid use in the NEOCOSUR Network was demonstrated.

Perinatal factors associated with neonatal mortality in very low birth weight infants: a multicenter study. / Factores perinatales asociados a la mortalidad neonatal en recién nacidos de muy bajo peso: estudio multicéntrico.

INTRODUCTION: Objectives. To assess risk factors associated withneonatal mortality in very low birth weight (VLBW) infants (< 1500 g) and the impact of the administration of antenatal corticosteroids. POPULATION AND METHODS: Retrospective analysis of a VLBW infant cohort from 26 tertiary care and teaching sites member of the South American Neonatal Network (NEOCOSUR), which includes Argentina, Brazil, Chile, Paraguay, Peru, and Uruguay, conducted between 2000 and 2011 on 11 455 records. Maternal and neonatal characteristics and morbidity were compared between deceased VLBW infants and those who survived to discharge. Outcome measures associated with neonatal mortality were established by logistic regression. The effect of antenatal corticosteroids on neonatal morbidity and mortality was estimated using the matching method. RESULTS: The neonatal mortality rate was 22.3%, and variability among sites was elevated. Factors that were independently associated with a lower mortality of VLBW infants included the administration of antenatal corticosteroids (OR: 0.49, 95% CI: 0.43-0.54), a better birth weight Z-score (OR: 0.63, 0.61-0.65), arterial hypertension (OR: 0.67, 0.58-0.77), and C-section (OR: 0.75, 0.65-0.85). The matching method allowed reducing the risk of death by 38% in association with antenatal corticosteroids. CONCLUSIONS: Major perinatal factors were identified in association with neonatal mortality in VLBW infants, and the impact of antenatal corticosteroid use in the NEOCOSUR Network was demonstrated.

INTRODUCCIÓN: Objetivos. Evaluar los factores de riesgo asociados a la mortalidad neonatal en recién nacidos de muy bajo peso (RNMBP, < 1500 g) y el impacto de la administración antenatal de corticoides. POBLACIÓN Y MÉTODOS: Análisis retrospectivo de una cohorte de RNMBP de 26 centros perinatales terciarios y universitarios de la Red Neonatal Sudamericana (NEOCOSUR), que incluye Argentina, Brasil, Chile, Paraguay, Perú y Uruguay, entre 2000 y 2011, y que cuenta con 11455 registros. Las características maternas, neonatales y la morbilidad se compararon entre los RNMBP que murieron y los sobrevivientes hasta el alta. Las variables asociadas con la muerte neonatal se determinaron mediante regresión logística. Se estimó el efecto del corticoide prenatal sobre la morbimortalidad neonatal utilizando el método de pareamiento. RESULTADOS: La tasa de mortalidad neonatal fue de 22,3% con una elevada variabilidad entre los centros. Los factores independientemente asociados a menor mortalidad de los RNMBP fueron la administración de corticoides prenatal (OR 0,49; IC 95%: 0,43-0,54), mejor puntaje Z del peso de nacimiento (OR 0,63; 0,61-0,65), hipertensión arterial (OR 0,67; 0,58-0,77) y cesárea (OR 0,75; 0,65-0,85). Mediante pareamiento, el riesgo de muerte se redujo en 38% asociado a los corticoides prenatales. CONCLUSIONES: Se identificaron importantes factores perinatales asociados con la mortalidad neonatal en RNMBP y se demostró el impacto de la administración de corticoides prenatales en la Red NEOCOSUR.

Prevalence and Virulence Genes of Shigella spp. Isolated from Patients with Diarrhea in Rosario, Argentina.

The aim of this study was to determine the prevalence and virulence factors of Shigella species isolated from patients with diarrhea. Shigella species were isolated from 1,022 stool samples collected from different hospitals in Rosario, Argentina. The isolates were characterized using phenotypic tests, serotyping, and detection of virulence genes by PCR. One hundred strains (9.8% of samples collected) of Shigella were isolated. Shigella flexneri was the most frequently identified species (74%), followed by S. sonnei (26%). S. flexneri was also the predominant species isolated from children aged 6-14 years. These clinical strains of Shigella were then tested for the presence of ipaH, virA, ial, sen, and set using specific primers. virA was present in all strains, whereas ipaH was detected in 98% of strains and ial in 83%. sen was found in 71.6% of S. flexneri and 42.3% of S. sonnei isolates, and 41.9% of S. flexneri isolates were positive for set. Furthermore, 32.4% of S. flexneri isolates were positive for both set and sen. This study provides data on the prevalence and distribution of diverse Shigella strains.