[What about the weekend effect? Impact of the day of admission on in-hospital mortality, length of stay and cost of hospitalization]. / ¿Qué hay del efecto fin de semana? Impacto del día de ingreso sobre la mortalidad intrahospitalaria, la duración de la estancia y el coste de la hospitalización.

INTRODUCTION: There is no agreement on the existence of the weekend effect in healthcare or, if it exists, on its possible causes. The objective of the study was to evaluate the differences in healthcare outcomes between patients admitted on weekdays or weekends in a high-complexity hospital. METHODS: Observational and retrospective study of patients admitted between 2016 and 2019 in a public hospital with more than 1300 beds. Hospitalization episodes were classified according to whether admission took place between Friday at 3:00 p.m. and the following Monday at 8:00 a.m. (weekend admission) or not (admission on weekdays). Mortality, length of stay and associated costs were compared, applying their respective risk-adjustment models. RESULTS: Of the total 169,495 hospitalization episodes analyzed, 48,201 (28.44%) corresponded to the weekend, presenting an older age (54.9 years vs. 53.9; P<.001), a higher crude mortality rate (5.22% vs. 4.59%; P<0.001), and a longer average length of stay (7.42 days vs. 6.74; P<.001), than those admitted on weekdays. The median crude cost of stay was lower (€731.25 vs. €850.88; P<0.001). No significant differences were found when applying the adjustment models, with a risk-adjusted mortality ratio of 1.03 (0.99-1.08) vs. 0.98 (0.95-1.01), risk-adjusted length of stay of 1.002 (0.98-1.005) vs. 0.999 (0.997-1.002) and risk-adjusted cost of stay of 0.928 (0.865-0.994) vs. 0.901 (0.843-0.962). CONCLUSION: The results of the study reveal that the assistance provided during the weekends does not imply worse health outcomes or increased costs. Comparing the impact between hospitals will require a future homogenization of temporal criteria and risk adjustment models.

Asociación del nivel socioeconómico y educacional en los egresos por cáncer de mama en Chile durante los años 2001 al 2016 / Association of the socioeconomic and educational level in the breast cancer hospital outbreaks in Chile during the years 2001 to 2016

Introducción: El cáncer de mama constituye la primera causa de muerte en los cánceres en Chile según Globocan 2018. Dentro de los factores que explican esta alta mortalidad encontramos una baja tasa de detección y de realización de mamografías en los niveles socioeconómicos altos. Es por esto que comprender las causas de defunción y los factores que afectan en la mortalidad y letalidad por cáncer de mama en los últimos 17 años nos permitirá enfocar las políticas públicas de los próximos 50 años. Los objetivos generales de este trabajo fueron caracterizar los egresos hospitalarios en los pacientes por cáncer de mama según la edad, el sexo, la previsión, el nivel socioeconómico y educacional en Chile durante los años 2001 al 2016 y calcular la mortalidad y letalidad específica en estas mismas variables durante los años 2001 a 2016. El objetivo específico es asociar las variables socioeconómicas y educacionales, estimando los Odd's ratios de las variables en los egresos hospitalarios por cáncer de mama en Chile durante los años 2001 al 2016. Materiales y Métodos: Estudio de cohorte longitudinal retrospectivo en 81,072 egresos hospitalarios y 20,220 defunciones obtenidas de la página DEIS MINSAL, años 2001-2016. Para el análisis univariado se efectuó una regresión de ajuste de tasas Prais-weinstein según edad y sexo según modelo OMS de ajuste de tasas. Para las variables de tipo discreta se describieron mediante porcentajes y tasas y para las variables de tipo continua se utilizó mediana y desviación estándar. Se efectuó un test de smirnov-kolmolgorov para determinar el tipo de distribución y de normalidad de las muestras. Para las variables de tipo dicotómica se utilizó un modelo de regresión logística binaria para describir estas variables y determinar la posible asociación entre el nivel socioeconómico y educacional de las pacientes diagnosticadas por cáncer de mama. Resultados: Murieron 1,88 veces más personas de nivel socioeconómico alto con un IC entre 1,83- 1,94 con respecto a la población de nivel socioeconómico bajo. En cambio, las personas con un mayor nivel educacional murieron 0,5 veces menos según la regresión realizada respecto al bajo nivel educacional con un IC entre 0,47- 0,52, pero a menor nivel educacional aumentó 20 veces la mortalidad, constituyendo una causa inversa. Respecto al sexo las mujeres murieron 2,08 veces más que los hombres. Para el nivel socioeconómico alto en relación al bajo un OR [1.88 (1.83 a 1,94)], p<0,0001], para el nivel educacional alto en relación al bajo fue a favor del mayor nivel educacional con OR [0,5 (0,47 - 0,52)] y en cuanto a la comparación de sexos un OR [1,04 (1,03-2,17), p=0,039]. Es decir, la diferencia entre mortalidad que hubo fue significativa para todos los intervalos tanto para sexo, nivel educacional como para nivel socioeconómico. Se encontró una constante de 0,013 de mortalidad basal, es decir, todos tienen 1,3% de riesgo de morir por cáncer de mama independiente del nivel socioeconómico, educacional y del sexo. Conclusión: Existen diferencias estadísticamente significativas respecto a la mortalidad entre los niveles socioeconómicos altos y bajos y también en nivel educacional, sin embargo, al realizar los métodos de regresión se obtuvo una mayor mortalidad y mayor riesgo de morir por cáncer de mama en los niveles socioeconómicos más altos asociados a, probablemente, la menor cantidad de tamizajes y realización de mamografías en este estrato. A partir del año 2008 se observó un incremento a los niveles originales observados al inicio del segundo milenio incrementando las diferencias existentes en los índices de desigualdad tanto por nivel educacional como por nivel socioeconómico incrementando en 20 veces respecto al nivel educacional, y 1.88 respecto al nivel socioeconómico.

Introduction: Breast cancer is the leading cause of death in cancers in Chile according to Globocan 2018. Among the factors that explain this high mortality, we find a low rate of detection and performance of mammograms in high socioeconomic levels. This is why understanding the causes of death and the factors that affect mortality and fatality from breast cancer in the last 17 years will allow us to focus on public policies for the next 50 years Materials and Methods: Retrospective longitudinal cohort study in 79,996 hospital discharges and 20,220 deaths obtained from the DEIS MINSAL page, years 2001 -2016. For the univariate analysis, a Prais-Weinstein rate adjustment regression was performed according to age and sex according to the WHO rate adjustment model. For discrete type variables, they were described by percentages and rates, and median and standard deviation were used for continuous type variables. A smirnov-kolmolgorov test was performed to determine the type of distribution and normality of the samples. For dichotomous variables, a binary logistic regression model was used to describe these variables and determine the possible association between the socioeconomic and educational level of the patients diagnosed with breast cancer. Abstract: In this observational, longitudinal and retrospective study with 101.292 patients that includes men and women of all ages with diagnosis of breast cancer all along Chile, we´ll analyze the impact of socioeconomic level, evaluated through educational level and money income, into the prevalence, mortality and lethality of breast cancer in the years 2001 to 2016. Results: People with a high socioeconomic level died 1.88 times more, with a CI between 1.83 and 1.94, than those with a low socioeconomic level. On the other hand, people with a higher educational level died 0.5 times less according to the regression carried out with respect to the low educational level with a CI between 0.47 and 0.52, but the lower the educational level the mortality increased 20 times, constituting an inverse cause. Regarding sex, women died 2.08 times more than men. For the high socioeconomic level in relation to the low one an OR [1.88 (1.83 to 1.94)], p<0.0001], for the high educational level in relation to the low one it was in favor of the higher educational level with OR [0.5 (0.47 - 0.52)] and as for the comparison of sexes an OR [1.04 (1.03-2.17), p=0.039]. In other words, the difference between mortality was significant for all the intervals for sex, educational level and socioeconomic level. A constant baseline mortality of 0.013 was found, i.e., everyone has a 1.3% risk of dying from breast cancer regardless of socioeconomic level, educational level and sex. Conclusions: There are statistically significant differences in mortality between high and low socioeconomic levels and also in educational level; however, when regression methods were used, a higher mortality and higher risk of dying from breast cancer was obtained in the higher socioeconomic levels, probably associated with the lower number of screenings and mammograms performed in this stratum. As of 2008, an increase to the original levels observed at the beginning of the second millennium was observed, increasing the existing differences in the inequality indexes both by educational level and socioeconomic level, increasing by 20 times with respect to educational level, and 1.88 times with respect to socioeconomic level.

CRISPR-Cas9-mediated knockout of GCN2 reveals a critical role in sensing amino acid deprivation in bovine mammary epithelial cells.

The objective of this study was to determine the role of GCN2 in the response to AA deprivation of primary bovine mammary epithelial cells (BMEC). Cells were isolated from the mammary tissue of 2 lactating Holstein cows by enzymatic digestion, expanded, and induced to differentiate for 5 to 7 d. Relative mRNA expression was measured by real-time quantitative PCR. Protein abundance and site-specific phosphorylation were measured by immunoblotting. Knockout of GCN2 in BMEC was accomplished by lentiviral delivery of a targeted single guide RNA and endonuclease Cas9. To investigate the role of GCN2, we treated lactogenic differentiated BMEC with either culture medium lacking Arg, Leu, and Lys combined or lacking only one of the 3 AA of interest, in comparison to a control with a full complement of AA. Activation of GCN2 was inferred by the phosphorylation status of its downstream target eIF2α Ser51. We found that GCN2 was activated by both the deprivation of Arg, Leu, and Lys combined and of Arg alone, as shown by a 2.73- and 2.82-fold increase in phosphorylated eIF2α Ser51 after 1 h of deprivation, respectively. In addition, activation of GCN2 as measured by increased phosphorylation of eIF2α Ser51 during the deprivation of Arg, Leu, and Lys combined and of Arg alone was sustained for up to 8 h of deprivation. Phosphorylated eIF2α selectively upregulates translation of transcription factor ATF4, among others, during AA deprivation, which then targets genes necessary for restoring AA homeostasis. Therefore, we investigated the expression of ATF4 transcriptional targets, AA enzyme ASNS and AA transporters SLC7A1 and SLC38A2. We found that ASNS was upregulated in response to combined AA deprivation and by Arg deprivation alone by 3.6- and 4.51-fold, respectively, at 24 h of treatment. We found that SLC7A1 was upregulated in response to combined AA deprivation and deprivation of Arg alone by 2.0- and 2.36-fold, respectively, at 8 h of treatment. To establish the role of GCN2 (encoded by EIF2AK4) in the response to AA deprivation, we ablated GCN2 in BMEC using clustered regularly interspaced short palindromic repeats-Cas9. We showed that BMEC transduced with single guide RNA targeting EIF2AK4 were not as responsive to combined AA deprivation, compared with BMEC transduced with nontargeting single guide RNA. Taken together, our results demonstrate a critical role for GCN2 in sensing AA deprivation in BMEC.

AMP-activated protein kinase controls lipid and lactose synthesis in bovine mammary epithelial cells.

The synthesis of milk components in bovine mammary epithelial cells (BMEC) requires an adequate supply of energy. The AMP-activated protein kinase (AMPK) is a cellular energy gauge that controls anabolic and catabolic processes to maintain a balance between energy supply and demand. The objectives of this study were to assess the role of AMPK on de novo lipid and lactose synthesis, as well as its regulation by glucose and acetate availability in BMEC. We isolated primary BMEC from the mammary tissue of 3 lactating Holstein cows and differentiated them with lactogenic hormones for 4 d. We measured protein abundance, site-specific phosphorylation, and proteolytic processing by immunoblotting. We quantified the expression of genes involved in lipid and lactose synthesis using real-time quantitative PCR. We measured de novo lipid and lactose synthesis by incorporation of radioactive substrates. We analyzed data by ANOVA using a randomized complete block design with PROC MIXED in SAS. To assess the effect of AMPK activation on milk component synthesis, we treated BMEC with 100 µM A-769662 (A76; an allosteric activator of AMPK) or vehicle control for 16 h. Consistent with activation of AMPK, A76 increased phosphorylation of its downstream targets ACC Ser79 and TSC2 Ser1387 by 144% and 26%, respectively. Activation of AMPK decreased lipid synthesis by 19%. This effect was accompanied by increased expression of FABP3. Activation of AMPK reduced the proportion of mature SREBP-1c. In addition, AMPK activation reduced lactose synthesis by 24% and lowered the expression of SLC2A1, the gene encoding GLUT1. To assess the regulation of AMPK by energy substrate availability, we incubated BMEC in a control medium containing 4 mM D-glucose and 1 mM sodium acetate, or medium lacking glucose or acetate, for 4 h. Compared with the control medium, deprivation of glucose or acetate promoted AMPKα phosphorylation at Thr172 by 84% or 58%, respectively. Activation of AMPK was significantly increased in BMEC only when the medium was devoid of glucose for at least 4 h. We concluded that activation of AMPK inhibits de novo lipid and lactose synthesis in BMEC. Further studies are needed to assess the physiological relevance of AMPK activation for milk composition in vivo and to identify the mechanisms mediating its effects on milk component synthesis.

Marcadores de selección en cerdos Pampa Rocha: comparación con razas autóctonas de España y Portugal / Selection markers in Pampa Rocha piqs: a comparison with autochthonous breeds of Spain and Portugal

RESUMEN Objetivo. El análisis de marcadores de selección permite obtener datos de la vida evolutiva de una raza o línea y permite también evaluar la conveniencia o no de su uso en programas de mejora genética. Hemos evaluado SNPs en cuatro genes (IGF2, MC4R, PRKAG3 y PEPCK-C), que tienen importantes efectos fenotípicos, en cerdos de la raza Pampa Rocha, una raza criolla, y hemos comparado sus frecuencias alélicas con cerdos de diversas razas autóctonas y líneas de España y Portugal no sometidas a selección así como con jabalíes y cerdos de la raza Piétrain. Materiales y métodos. Los SNPs fueron analizados mediante diversas técnicas de RT-PCR. Resultados. Los resultados de los análisis muestran una similitud de frecuencias alélicas entre los cerdos de la raza Pampa Rocha y los cerdos autóctonos de la península ibérica sobre todo en el gen IGF2 y, en menor medida en el gen PEPCK-C. Sin embargo difieren considerablemente en el caso del marcador MC4R y, también en menor medida, en PRKAG3. En el trabajo se discute el uso potencial de los resultados obtenidos para orientar la selección genética de cerdos de la raza Pampa Rocha. Conclusiones. Nuestros resultados demuestran la peculiaridad de la raza Pampa Rocha con respecto a los marcadores estudiados.

ABSTRACT Objective. The analysis of selection markers allows to obtain information about the evolutive story of a particular breed or line and allows also to evaluate the usefulness of those markers for breeding programs. We have analyzed SNPs in four genes of the creole pig breed Pampa Rocha and we have compared their allelic frequencies with the allelic frequencies of diverse autochthonous breeds of Spain and Portugal and also with Piétrain pigs and wild boars. Materials and methods. The SNPs were analyzed using diverse RT-PCR methods. Results. The results of the analysis show that Pampa Rocha pigs have similar allelic frequencies with the autochthonous breeds of Spain and Portugal especially in the case of IGF2 and also, but not so coincident, in the case of PEPCK-C. However, they differ considerably for MC4R, and also, but in a lower extent, for PRKAG3. We discuss in this work the usefulness of our results for breeding of Pampa Rocha pigs. Conclusions. Our results demonstrate the peculiarity of the Pampa Rocha breed regarding the markers studied.

Estilo de vida y distribución de grasa en adolescentes asmáticos y sanos / Lifestyle and Fat Distribution in Asthmatic and Healthy Adolescents

Introducción: el objetivo es analizar el estilo de vida, en función del ejercicio y la dieta, de un grupo de adolescentes de la Comunidad de Madrid, teniendo en cuenta género y patología y su relación con el estado nutricional, la distribución de grasa y la función pulmonar. Metodología: Estudio descriptivo de 207 sujetos que analizó el estilo de vida a partir del nivel de actividad física (AF) y la adherencia a la dieta mediterránea, el estado nutricional y la distribución de grasa, y la salud respiratoria. Resultados: El grupo de no asmáticos fue más activo (p=0,003) y presentó menor ICT (p=0,001) que el grupo de asmáticos. Se encontraron diferencias significativas dentro del grupo sin asma en nivel de AF siendo los varones más activos (p=0,01) y presentando menor índice cintura-talla (ICT) que las mujeres del mismo grupo (p=0,001). Conclusiones: Los adolescentes no asmáticos fueron más activos y presentaron mejor distribución de grasa que los asmáticos

Objectives: objective is to analyze the lifestyle, integrating exercise and diet, of a group of adolescents from the Community of Madrid, taking into account gender and pathology and its relationship with nutritional status, fat distribution and lung function in adolescents with or without asthma. Methods: This was a descriptive study including 207 subjects aged 13.20 ± 0.62 years. Lifestyle was assessed in terms of physical activity (PA) levels, Mediterranean diet, nutritional status, and respiratory health measured through FEV1 (z). Results: In the non-asthma group, boys were more active (p = 0.01) and showed a lower waist-to-height ratio (WHtR) than girls (p = 0.001). Participants without asthma were more active (p = 0.003), and had a better WHtR (p = 0.001) and FEV1 (p = 0.001) than those with asthma. Conclusions: In this Spanish population sample, non-asthmatic adolescents were more active and showed a better nutritional status, fat distribution and respiratory health than their peers with asthma

Effect of feeding system and grain source on lactation characteristics and milk components in dairy cattle.

The objective of this study was to examine the effect of feeding systems [component and total mixed rations (TMR)] and dietary grain sources (barley, commercial concentrate, corn grain, and high-moisture corn) on lactation characteristics and milk composition. A total of 852,242 test-day records, information on animal characteristics, feed composition, and feeding systems from 104,129 Holstein cows in 4,319 herds covering a period of 5 yr were obtained from Quebec's Dairy Herd Improvement Association (Valacta). We performed descriptive statistics and graphical representations of the data for each type of feeding system and grain source by parity (1 to 3). The milk records were binned in 15-d in milk blocks. Mixed models using a combination of forward and backward stepwise selections were developed to predict milk and milk component yields. The TMR-fed cows had greater yield of milk, fat, protein, and lactose and lower milk urea N (MUN) concentration than component-fed cows at all parities. Cows fed a TMR had higher peak milk yields and greater persistency after peak lactation compared with component-fed cows. In addition, greater yields of milk fat and protein from peak to mid-lactation were found in TMR- versus component-fed cows. In general, greater milk fat and protein yields as well as lower MUN concentration were observed in cows fed corn grain or high-moisture corn compared with barley or commercial concentrate, but parity influenced these relationships. The feeding system by day in milk blocks interaction was significant in models of milk and components yields for all parities, but only for second-lactation cows for MUN concentration. This means that effect of TMR and component feeding differs with stage of lactation. In conclusion, feeding TMR and corn-based diets are associated with greater yield of milk and milk components under commercial conditions.

Short communication: Urea hydrolysis in dairy cattle manure under different temperature, urea, and pH conditions.

The objective of the study was to quantify the rate of urea hydrolysis in dairy cattle manure under different initial urea concentration, temperature, and pH conditions. In particular, by varying all 3 factors simultaneously, the interactions between them could also be determined. Fresh feces and artificial urine solutions were combined into a slurry to characterize the rate of urea hydrolysis under 2 temperatures (15°C and 35°C), 3 urea concentrations in urine solutions (500, 1,000, and 1,500 mg of urea-N/dL), and 3 pH levels (6, 7, and 8). Urea N concentration in slurry was analyzed at 0.0167, 1, 2, 4, 6, 8, 12, 16, 20, and 24 h after initial mixing. A nonlinear mixed effects model was used to determine the effects of urea concentration, pH, and temperature treatments on the exponential rate of urea hydrolysis and to predict the hydrolysis rate for each treatment combination. We detected a significant interaction between pH and initial urea level. Increasing urea concentration from 1,000 to 1,500 mg of urea-N/dL decreased the rate of urea hydrolysis across all pH levels. Across all pH and initial urea levels, the rate of urea hydrolysis increased with temperature, but the effect of pH was only observed for pH 6 versus pH 8 at the intermediate initial urea concentration. The fast rates of urea hydrolysis indicate that urea was almost completely hydrolyzed within a few hours of urine mixing with feces. The estimated urea hydrolysis rates from this study are likely maximum rates because of the thorough mixing before each sampling. Although considerable mixing of feces and urine occurs on the barn floor of commercial dairy operations from cattle walking through the manure, such mixing may be not as quick and thorough as in this study. Consequently, the urea hydrolysis rates from this study indicate the maximum loss of urea and should be accounted for in management aimed at mitigating ammonia emissions from dairy cattle manure under similar urea concentration, pH, and temperature conditions reported in this experiment.

Emerging infectious diseases and public health policy: insights from Cambodia, Hong Kong and Indonesia.

Emerging infectious diseases affect the health of animal and human populations, but the impact goes beyond health as it extends to political, economic, social and environmental domains, as well as inter-state relations. Deeper understanding of these impacts aids public health authorities in their duties of protection and improvement of the health of their communities, promotion of healthy practices and research on disease, injury and threat prevention and mitigation. This empirical essay gathers insights from Cambodia, Hong Kong and Indonesia as they attempt to design and implement control and surveillance systems against avian influenza - an infectious disease.

Malformación arterio-venosa uterina y hemorragia obstétrica: diagnóstico y manejo en tres casos clínicos / Uterine arteriovenous malformation and obstetric hemorrhage: diagnosis and management in three cases

Las malformaciones vasculares uterinas son muy infrecuentes y se presentan asociadas a metrorragia con riesgo vital. Su incidencia no es conocida porque las series son de pocos casos. Presentamos tres pacientes con hemorragia obstétrica cuyo estudio diagnóstico con ultrasonido y angiografía, demostró malformación arteriovenosa uterina. En un caso, dada la extensión de la lesión, el tratamiento fue con embolización bilateral de arterias uterinas seguida de histerectomía. Otras dos pacientes, por preservación de fertilidad, fueron sometidas solo a embolización. La evolución clínica y las imágenes confirmaron que los procedimientos fueron exitosos. Se discute la importancia de la interpretación correcta de las imágenes para el diagnóstico, la adaptación de los métodos terapéuticos al caso individual y el manejo multidisciplinario.

The uterine vascular malformations are very infrequent and associated to maternal hemorrhage with vital risk. The incidence is unknown because the published series are little with few cases. We described three cases with obstetrical hemorrhage and the image study with ultrasound and angiography showed an arteriovenous malformation. One patient, for the extensive lesion, was treated with bilateral embolization of uterine arteries and then, histerectomy. The others patients, for preservation her fertility, were treated with embolization only. The clinical evolution and the vascular images study confirm the success of the procedures. We discuss the importance of images analysis for the diagnosis, the individual application of therapeutic methods and a multidisciplinary approach for this scope.

Alteraciones morfológicas del bazo de ratas (rattus norvergicus), tratadas con trióxido de arsénico / Morphological alterations of the spleen of rats (rattus norvegicus) treated with arsenic trioxide

En América Latina la presencia del arsénico en el ambiente y en las fuentes de agua para consumo humano, se debe a factores naturales de origen geológico como a actividades antropogénicas. El arsénico en las aguas naturales se encuentra principalmente como trivalente (arsenito) o pentavalente (arsenato). El objetivo de este trabajo fue determinar las alteraciones que provoca el trióxido de arsénico a nivel de la morfología del bazo de ratas (Rattus norvegicus - Sprague-Dawley). Se utilizaron 24 ratas de ambos sexos de 55 días de vida. Las ratas fueron pesadas y divididas en 3 grupos (4 hembras y 4 machos). Los grupos tratados fueron inyectados con 5 mg y 10 mg de As2O3 respectivamente, en dosis única diaria vía intraperitoneal por 15 días. Al grupo control se le aplicó agua destilada sin arsénico. Después del tratamiento los animales fueron sacrificados por eutanasia convencional y se obtuvo el bazo, los cuales fueron lavados, pesados y seccionados en cuatro partes, que fueron fijadas en formol tamponado al 10 por ciento. Mediante técnica histológica se obtuvieron 4 muestras seriadas de cada bazo, de 5 micrones de espesor con una separación de 100 micrones entre si. Posteriormente fueron teñidas con H-E. Se analizaron 30 campos (120 campos por órgano). Los datos obtenidos permiten concluir que ratas tratadas con trióxido de arsénico, presentan alteración a nivel de los compartimentos del bazo, con un aumento del compartimento de la pulpa roja, una depleción en el tamaño y número de folículos linfoides y de la zona marginal. A su vez, se observó pérdida de la celularidad de la vaina linfoide periarteriolar (PALS).

In Latin America, the presence of arsenic in the environment and water sources for human consumption is due to natural geological factors and anthropogenic activities. Arsenic in natural waters is mainly found as trivalent (arsenite) or pentavalent (arsenate). The aim of this study was to determine the alterations causing arsenic trioxide-level morphology of the spleen of rats (Rattus norvegicus - Sprague-Dawley). Were used 24 rats of both sexes of 55 days of life. The rats were weighed and divided into 3 groups (4 females and 4 males). The treated groups were injected with 5 mg and 10 mg of As2O3 respectively, intraperitoneally daily dosing for 15 days. The control group was administered arsenic-free distilled water. After treatment the animals were euthanized conventionally, and spleen was removed, which was washed, weighed and sectioned into four parts, which were fixed in 10 percent buffered formalin. Histological technique using four serial samples were obtained from each spleen of 5 microns thick with a spacing of 100 microns between them. Subsequently these were stained with H-E. We analyzed 30 fields (120 fields per organ). The data obtained indicates that rats treated with arsenic trioxide have an altered level of the compartments of the spleen, with an increased red pulp chamber, depletion in the size and number of lymphoid follicles and marginal zone. Furthermore, loss of cellularity of periarteriolar lymphoid sheath (PALS) was observed.

Embryo apoptosis may be a significant contributing factor in addition to aneuploidy inhibiting live deliveries once a woman reaches age 45.

PURPOSE: To determine the relative role of aneuploidy vs embryo apoptosis as the etiologic factor of poor pregnancy rates with advancing age. MATERIALS AND METHODS: A retrospective review of chemical vs clinical vs live delivery pregnancy rates in women aged 40-42, 43-45, and > or = 45 years is reported. The data were further stratified according to oocyte reserve based on day 3 serum follicle-stimulating hormone (FSH) < or = 11 mIU/ml vs >12 mIU/ml. RESULTS: For women aged 40-42 years there were no differences in live delivery pregnancy rates in women with normal vs decreased egg reserve (DOR). There were no differences in live delivery pregnancy rates in women aged 40-42 years vs 43-44 years with normal oocyte reserve; however despite no differences in clinical pregnancy rates in women aged 43-44 years with normal vs DOR, the live delivery pregnancy rates were markedly lower in the group with DOR. In contrast, there were very low chemical pregnancy rates in women aged > or = 45 years. CONCLUSIONS: As seen in younger women, there does not appear to be any increased risk of meiosis errors in women aged 40-42 years with DOR compared to women of the same age with normal reserve. Low pregnancy rates in women aged 43-44 years with DOR is related to meiosis errors. In contrast the very low chemical pregnancy rates found in women aged > or = 45 years despite embryo transfer (ET) suggest embryo apoptosis is mostly responsible for poor pregnancy rates in this very advanced reproductive age group.

Energy depletion of bovine mammary epithelial cells activates AMPK and suppresses protein synthesis through inhibition of mTORC1 signaling.

The molecular mechanisms by which cellular energy status regulates global protein synthesis in mammary epithelial cells have not been characterized. The objective of this study was to examine the effect of AMP-activated protein kinase (AMPK) activation by 2-deoxyglucose on protein synthesis and the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway in bovine mammary epithelial cells. Phosphorylation of AMPK at Thr172 increased by 1.4-fold within 5 min, and remained elevated throughout a 30-min time course, in response to 2-deoxyglucose. Global rates of protein synthesis declined by 78% of control values. The decline in protein synthesis was associated with repression of mTORC1 signaling, as indicated by reduced phosphorylation of ribosomal protein S6 kinase 1 and eIF4E binding protein-1 (4E-BP1). Phosphorylation of ER-stress marker eIF2α was also increased but only at 30 min of 2-deoxyglucose exposure. 2-Deoxyglucose increased phosphorylation of tuberous sclerosis complex 2 (TSC2) on AMPK consensus sites but did not change the amount of TSC1 bound to TSC2. Activation of AMPK did not result in changes in the amount of raptor bound to mTOR. The inhibitory effects of AMPK activation on mTORC1 signaling were associated with a marked increase in Ser792 phosphorylation on raptor. Collectively, the results suggest that activation of AMPK represses global protein synthesis in mammary epithelial cells through inhibition of mTORC1 signaling.

Técnica y resultados con reconstrucción pancreato-gástrica ducto-mucosa en pancreatoduodenectomy / Duct-to-mucosa pancreaticogastrostomy after pancreatoduodenectomy: experience in 37 patients

Background: Pancreatic reconstruction in pancreatoduodenectomy (PD) has many technical options. Evidence shows no difference in pancreatic fistula rate or mortality between pancretogastrostomy and pancrea-ticojejunostomy reconstruction. Aim: To report the results of the technique used by our team to perform duct-to-mucosa pancreaticogastrostomy (DMPG) in PD. Material and Methods: Follow up of 37 patients aged 53 +/- 12 years (59 percent women), subjected to pancreatoduodenectomy, using DMPG. Perioperative complications were reported using the Dindo-Clavien classification. Results: All patients had a pancreatic cancer. The tumor was located in the head or ampulla of Vater in 38 percent of patients. The most common histological type was adenocarcinoma in 33 patients (89 percent). Seventy three percent of patients did not have regional lymph node involvement (NO). Two patients died (5 percent). Postoperative complications were registered in 35 percent of patients. Two patients developed pancreatic fistulas, that were type A and B I one patient each, according to the classification of the International Study Group on Pancreatic Fistula. Conclusions: The morbidity and mortality associated with DMPG in PD in the reported cohort are comparable to those reported by other local studies.

Introducción: Para la reconstrucción pancreática en pancreatoduodenectomía (PD) existen diversas técnicas; la evidencia científica no demuestra diferencia en el porcentaje de fístulas pancreáticas ni morbi-mortalidad entre la reconstrucción con pancreatogastrostomía y pancreatoyeyunostomía. Nuestro objetivo es describir la técnica de pancreato-gastro anastomosis ducto-mucosa (PGADM) y los resultados en términos de morbimortalidad de esta técnica utilizada para la reconstrucción pancreática en PD. Material y Método: Estudio de serie de casos con seguimiento. Se incluyeron pacientes mayores de 15 años que fueron sometidos a PD y en los cuales se realizó reconstrucción pancreática con PGADM por el equipo de cirugía hepatopancreática y biliar del Hospital Regional de Temuco desde 1996 hasta 2010. Se reportó morbilidad perioperatoria según la clasificación de Dindo-Clavien. Se aplica estadística descriptiva. Resultados: La cohorte está constituida por 37 pacientes, la edad promedio fue 53 +/- 12 años y el 59 por ciento género masculino. Todos los pacientes tienen confirmación histopatológica de neoplasia, siendo los orígenes más frecuentes la cabeza del páncreas y ampolla de Vater con un 38 por ciento. El tipo histológico más frecuente fue el adenocarcinoma en 33 pacientes (89 por ciento). El 73 por ciento de los pacientes no tenía compromiso de ganglios linfáticos regionales (N0). La morbilidad peri operatoria fue de 35 por ciento. Dos pacientes presentaron fístulas pancreáticas (5,4 por ciento), uno tipo A y otra tipo B según la clasificación de la ISGPF. La mortalidad perioperatoria es de 2 pacientes (5 por ciento). Conclusiones: La morbi-mortalidad asociada a PD con reconstrucción pancreática con PGADM es comparable a la reportada por series nacionales.

Efecto en la estructura histológica del timo de ratas Sprague-Dawley tratadas con trióxido de arsénico / Effect on the histological structure of thymus on Sprague-Dawley treated with arsenic trioxide

En las áreas costeras del norte de Chile es común encontrar en el agua para consumo humano niveles medios o altos de arsénico. La exposición al arsénico puede ir asociada a efectos agudos o crónicos. El objetivo de esta investigación fue determinar el daño histológico que provoca el trióxido de arsénico a nivel de los compartimentos del timo de ratas Sprague-Dawley. Se utilizaron 24 ratas de ambos sexos de 55 días de vida. Las ratas fueron pesadas y divididas en 3 grupos (4 hembras y 4 machos). A los grupos tratados se les aplicó 5 mg y 10 mg de As2O3 respectivamente, en dosis única diaria vía intraperitoneal por 15 días. Al grupo control se le aplicó agua destilada sin arsénico. Después del tratamiento los animales fueron sacrificados y retirado el timo de ellos, los cuales fueron lavados, pesados y seccionados en dos, luego se fijaron en formol tamponado al 10 por ciento. Mediante técnica histológica convencional se obtuvieron 4 muestras seriadas de cada timo, de 5 um de espesor y separadas por 100 um entre si, luego fueron teñidas con H-E. Se analizaron 30 campos (120 campos por órgano). Los resultados muestran que el As2O3 provoca la pérdida de celularidad en ambos compartimentos del timo, tanto en la corteza como en la médula, viéndose más afectado el compartimento medular (junto a la unión corticomedular). Se observó una reducción significativa del tamaño de la zona medular en ambos grupos tratados (5 y 10 mg de As2O3 respectivamente), siendo probablemente la disminución de este tejido el responsable de la atrofia del timo. Además se observó un aumento del tamaño de la corteza en las ratas hembras tratadas con 10 mg de As2O3. La unión corticomedular de las ratas tratadas se observó difusa o difícil de distinguir.

In coastal areas of northern Chile medium or high levels of arsenic are commonly found in drinking water. Arsenic exposure may be associated with acute or chronic effects. The objective of this investigation was to determine the histological damage caused by arsenic trioxide level of the compartments of the thymus of Sprague-Dawley rats. We used 24 rats of both sexes of 55 days of life. The rats were weighed and divided into 3 groups (4 females and 4 males). In the treated groups were administered 5 mg and 10 mg of As2O3 respectively, in a single daily dose for 15 days intraperitoneally. The control group was administered distilled water without arsenic. After treatment the animals were sacrificed and the thymus removed, washed, weighed and divided into two, then fixed in 10 percent buffered formalin. By conventional histology samples were obtained serially every 4 thymus, 5 microns thick and separated by 100 microns each, then were stained with HE. We analyzed 30 fields (120 fields per organ). The results showed that As2O3 causes loss of cellularity in both compartments of the thymus, both in the cortex and in the bone, medullary compartment was more affected (near the corticomedullary junction). There was a significant reduction in the size of the medulla in both groups (5 and 10 mg As2O3 respectively), probably the decrease of the tissue responsible for thymic atrophy. We observed an increase in the size of the cortex in female rats treated with 10 mg of As2O3. The corticomedullary junction of the treated rats showed diffuse or difficult to distinguish.

Hyperaminoacidaemia at postprandial levels does not modulate glucose metabolism in type 2 diabetes mellitus.

AIMS/HYPOTHESIS: Hyperaminoacidaemia attenuates glucose disposal during hyperinsulinaemic clamps in healthy lean individuals, an effect thought to be mediated by negative feedback on insulin signalling, downstream of the mammalian target of rapamycin (mTOR) signalling pathway. This has been interpreted as amino acids causing insulin resistance in healthy people, and contributing to it in type 2 diabetes. However, the effect of hyperaminoacidaemia on glucose disposal in type 2 diabetic individuals remains to be determined. METHODS: Eight obese men with type 2 diabetes underwent a two-step hyperinsulinaemic-hyperglycaemic (8 mmol/l) clamp, first with amino acids at postabsorptive concentrations, followed by postprandial concentrations. Whole-body glucose turnover was assessed using D: -[3-(3)H]glucose. Vastus lateralis biopsies were obtained at baseline and during each step of the clamp to determine the phosphorylation states of AKT, mTOR, ribosomal protein (rp) S6, and insulin receptor substrate (IRS)-1. RESULTS: Rates of glucose infusion (1.30 ± 0.19 vs 1.15 ± 0.13 mmol/min), endogenous glucose production (0.48 ± 0.06 vs 0.53 ± 0.05 mmol/min) and disposal (1.24 ± 0.17 vs 1.17 ± 0.14 mmol/min) did not differ between postabsorptive and postprandial amino acid concentrations (p > 0.05). Whereas phosphorylation of AKT(Ser473), AKT(Thr308) mTOR(Ser2448) and rpS6(Ser235/236) increased (p < 0.05) with elevated amino acids, that of IRS-1(Ser636/639) and IRS-1(Ser1101) did not change. CONCLUSIONS/INTERPRETATION: Postprandial circulating amino acid concentrations do not worsen the already attenuated glucose disposal in hyperglycaemic type 2 diabetic men, and cell-signalling events are consistent with this. Our results do not support recommendations to restrict dietary protein in type 2 diabetes.

Cánceres ginecológicos y colorectal: riesgos y beneficios con el uso de anticonceptivos / Gynecological and colorectal cancers: risks and benefits with contraceptive use

Los cánceres genecológicos y colorectales se asocian a nivel mundial a importantes tasas de morbilidad y mortalidad. Tanto en estudios de cohorte, como de casos y controles se ha establecido una disminución del riesgo para los cánceres ginecológicos y colorectal asociado al uso de algunos métodos anticonceptivos (MAC)...