Cellular Senescence Is Immunogenic and Promotes Antitumor Immunity.

Cellular senescence is a stress response that activates innate immune cells, but little is known about its interplay with the adaptive immune system. Here, we show that senescent cells combine several features that render them highly efficient in activating dendritic cells (DC) and antigen-specific CD8 T cells. This includes the release of alarmins, activation of IFN signaling, enhanced MHC class I machinery, and presentation of senescence-associated self-peptides that can activate CD8 T cells. In the context of cancer, immunization with senescent cancer cells elicits strong antitumor protection mediated by DCs and CD8 T cells. Interestingly, this protection is superior to immunization with cancer cells undergoing immunogenic cell death. Finally, the induction of senescence in human primary cancer cells also augments their ability to activate autologous antigen-specific tumor-infiltrating CD8 lymphocytes. Our study indicates that senescent cancer cells can be exploited to develop efficient and protective CD8-dependent antitumor immune responses. SIGNIFICANCE: Our study shows that senescent cells are endowed with a high immunogenic potential-superior to the gold standard of immunogenic cell death. We harness these properties of senescent cells to trigger efficient and protective CD8-dependent antitumor immune responses. See related article by Chen et al., p. 432. This article is highlighted in the In This Issue feature, p. 247.

Interobserver variability in gross tumor volume contouring in non-spine bone metastases.

Background and Aim: The optimal imaging test for gross tumor volume (GTV) delineation in non-spine bone metastases has not been defined. The use of stereotactic body radiotherapy (SBRT) requires accurate target delineation. Magnetic resonance imaging (MRI) and/or 18fludesoxyglucose positron emission tomography (18FDG-PET) allow for better visualization of the extent of bone metastases and optimizes the accuracy of tumor delineation for stereotactic radiotherapy compared to computed tomography (CT) alone. We evaluated the interobserver agreement in GTV of non-spine bone metastases in a single center and compared MRI and/or 18FDG-PET and CT in GTV delineation. Methods: Anonymous CT and MRI and/or 18FDG-PET obtained from 10 non-spine bone metastases were analyzed by six radiation oncologists at our center. Images acquired by CT and MRI and/or 18FDG-PET were used to delineate 10 GTVs of non-spine bone metastases in the pelvis, extremities, and skull. The cases showed different characteristics: blastic and lytic metastases, and different primary cancers (lung, breast, prostate, rectum, urothelial, and biliary). In both CT and MRI and/or 18FDG-PET, the GTV volumes were compared. The index of agreement was evaluated according to Landis and Koch protocol. Results: The GTV volume as defined on MRI was in all cases larger or at least as large as the GTV volume on CT (P=0.25). The median GTV volume on MRI was 3.15 cc (0.027-70.64 cc) compared to 2.8 cc on CT (0.075-77.95 cc). Interobserver variance and standard deviation were lower in CT than MRI (576.3 vs. 722.2 and 24.0 vs. 26.9, respectively). The level of agreement was fair (kappa=0.36) between CT and MRI. The median GTV volume on 18FDG-PET in five patients was 5.8 cc (0.46-64.17 cc), compared to 4.1 cc on CT (0.99-54.2 cc) (P=0.236). Interobserver variance and standard deviation in CT, MRI, and 18FDG-PET were 576.3 versus 722.2 versus 730.5 and 24 versus 26.9 versus 27.0, respectively. The level of agreement was slight (kappa=0.08) between CT and 18FDG-PET. Conclusions: Interobserver variance in non-spine bone metastases was equal when MRI and PET were compared to CT. CT was associated with the lowest variance and standard deviation. Compared to CT GTVs, the GTVs rendered from MRI images had fair agreement, while the GTVs rendered from 18FDG-PET had only slight agreement. Relevance for Patients: The delimitation of the treatment volume in non-spine bone metastases with SBRT is important for the results determining its efficacy. It is therefore essential to know the variability and to manage it to achieve the highest quality of treatment.

A ketogenic diet impacts markers of mitochondrial mass in a tissue specific manner in aged mice.

Declines in mitochondrial mass are thought to be a hallmark of mammalian aging, and a ketogenic diet (KD) may prevent the age-related decreases in mitochondrial content. The objective of this study was to investigate the impact of a KD on markers of mitochondrial mass. Mice were fed an isocaloric control diet (CD) or KD from 12 months of age. Tissues were collected after 1 month and 14 months of intervention, and a panel of commonly used markers of mitochondrial mass (mitochondrial enzyme activities and levels, mitochondrial to nuclear DNA ratio, and cardiolipin content) were measured. Our results showed that a KD stimulated activities of marker mitochondrial enzymes including citrate synthase, Complex I, and Complex IV in hindlimb muscle in aged mice. KD also increased the activity of citrate synthase and prevented an age-related decrease in Complex IV activity in aged brain. No other markers were increased in these tissues. Furthermore, the impacts of a KD on liver and kidney were mixed with no pattern indicative of a change in mitochondrial mass. In conclusion, results of the present study suggest that a KD induces tissue-specific changes in mitochondrial enzyme activities, or structure, rather than global changes in mitochondrial mass across tissues.

A Two-Photon Probe Based on Naphthalimide-Styrene Fluorophore for the In Vivo Tracking of Cellular Senescence.

Cellular senescence is a state of stable cell cycle arrest that can negatively affect the regenerative capacities of tissues and can contribute to inflammation and the progression of various aging-related diseases. Advances in the in vivo detection of cellular senescence are still crucial to monitor the action of senolytic drugs and to assess the early onset or accumulation of senescent cells. Here, we describe a naphthalimide-styrene-based probe (HeckGal) for the detection of cellular senescence both in vitro and in vivo. HeckGal is hydrolyzed by the increased lysosomal ß-galactosidase activity of senescent cells, resulting in fluorescence emission. The probe was validated in vitro using normal human fibroblasts and various cancer cell lines undergoing senescence induced by different stress stimuli. Remarkably, HeckGal was also validated in vivo in an orthotopic breast cancer mouse model treated with senescence-inducing chemotherapy and in a renal fibrosis mouse model. In all cases, HeckGal allowed the unambiguous detection of senescence in vitro as well as in tissues and tumors in vivo. This work is expected to provide a potential technology for senescence detection in aged or damaged tissues.

Effect of a load distribution system on mobility and performance during simulated and field hiking while under load.

This study was conducted to test a modular scalable vest-load distribution system (MSV-LDS) against the plate carrier system (PC) currently used by the United States Marine Corps. Ten Marines engaged in 1.6 km load carriage trials in seven experimental conditions in a laboratory study. Kinematic, kinetic, and spatiotemporal gait parameters, muscle activity (electromyography), heart rate, caloric expenditure, shooting reaction times, and subjective responses were recorded. There was lower mean trapezius recruitment for the PC compared with the MSV-LDS for all conditions, and muscle activity was similar to baseline for the MSV-LDS. Twenty-seven Marines carrying the highest load were evaluated in the field, which measured an increase in energy expenditure with MSV-LDS; however, back discomfort was reduced. The field evaluation showed significantly reduced estimated ground reaction force on flat-ground segments with the MSV-LDS, and the data suggest both systems were comparable with respect to mobility and energy cost. Practitioner summary: This study found that a novel load distribution system appears to redistribute load for improved comfort as well as reduce estimated ground reaction force when engaged in hiking activities. Further, hiking with a load distribution system enables more neutral walking posture. Implications of load differences in loads carried are examined. Abbreviations: AGRF: anterior-posterior ground reaction forces; CAREN: Computer Assisted Rehabilitation Environment; GRF: ground reaction forces; HR: heart rate; ML-GRF: mediolateral ground reaction forces; MOLLE: Modular Lightweight Load-carrying Equipment; MSV-LDS: modular scalable vest-load distribution system; NHRC: Naval Health Research Center; PC: plate carrier; PPE: personal protective equipment; RPE: rating of perceived exertion; SAPI: small arms protective insert; sEMG: surface electromyography; USMC: United States Marine Corps; VGRF: Ground reaction forces in the vertical.

The Impact of Aging, Calorie Restriction and Dietary Fat on Autophagy Markers and Mitochondrial Ultrastructure and Dynamics in Mouse Skeletal Muscle.

Loss of skeletal muscle mass and function is a hallmark of aging. This phenomenon has been related to a dysregulation of mitochondrial function and proteostasis. Calorie restriction (CR) has been demonstrated to delay aging and preserve function until late in life, particularly in muscle. Recently, we reported the type of dietary fat plays an important role in determining life span extension with 40% CR in male mice. In these conditions, lard fed mice showed an increased longevity compared to mice fed soybean or fish oils. In this article, we analyze the effect of 40% CR on muscle mitochondrial mass, autophagy, and mitochondrial dynamics markers in mice fed these diets. In CR fed animals, lard preserved muscle fibers structure, mitochondrial ultrastructure, and fission/fusion dynamics and autophagy, not only compared to control animals, but also compared with CR mice fed soybean and fish oils as dietary fat. We focus our discussion on dietary fatty acid saturation degree as an essential predictor of life span extension in CR mice.

Causa muy rara de pubertad precoz periférica en una niña: tumor de cordones sexuales con túbulos anulares / A very rare cause of peripheral precocious puberty in a girl: ovarian sex cord tumor with annular tubules

El tumor de los cordones sexuales con túbulos anulares es una neoplasia del estroma gonadal muy infrecuente. Representa el 0,05-0,6% de todos los tumores ováricos, según series. Se presenta un caso especialmente inusual, en una niña de 6 años, detectado a raíz de una pubertad precoz periférica isosexual. Su interés radica en que no se halló ninguna masa anexa al ovario, sino únicamente una asimetría gonadal, sin signos radiológicos de malignidad. Se realizó una salpingo-ooforectomía unilateral con linfadenectomía pélvica y paraaórtica ipsilateral, por vía laparoscópica, tras confirmarse la presencia de células tumorales en la biopsia intraoperatoria. La evolución posterior de la paciente fue favorable.

Sex cord tumor with annular tubules is an extremely uncommon gonadal stromal neoplasm. It represents 0.05-0.6% of all ovarian tumors, according to series. An unusual case is presented in a 6-year-old girl, detected as a result of an isosexual peripheral precocious puberty. The highlight of this case is that no mass attached to the ovary was found, but only a gonadal asymmetry without radiological signs of malignancy. After confirming the presence of tumoral cells by intraoperative biopsy, unilateral salpingo-oophorectomy with ipsilateral para-aortic and pelvic lymphadenectomy was performed. Afterwards, the evolution of the patient was favorable.

[A very rare cause of peripheral precocious puberty in a girl: ovarian sex cord tumor with annular tubules]. / Causa muy rara de pubertad precoz periférica en una niña: tumor de cordones sexuales con túbulos anulares.

Sex cord tumor with annular tubules is an extremely uncommon gonadal stromal neoplasm. It represents 0.05-0.6% of all ovarian tumors, according to series. An unusual case is presented in a 6-year-old girl, detected as a result of an isosexual peripheral precocious puberty. The highlight of this case is that no mass attached to the ovary was found, but only a gonadal asymmetry without radiological signs of malignancy. After confirming the presence of tumoral cells by intraoperative biopsy, unilateral salpingo-oophorectomy with ipsilateral para-aortic and pelvic lymphadenectomy was performed. Afterwards, the evolution of the patient was favorable.

El tumor de los cordones sexuales con túbulos anulares es una neoplasia del estroma gonadal muy infrecuente. Representa el 0,05-0,6% de todos los tumores ováricos, según series. Se presenta un caso especialmente inusual, en una niña de 6 años, detectado a raíz de una pubertad precoz periférica isosexual. Su interés radica en que no se halló ninguna masa anexa al ovario, sino únicamente una asimetría gonadal, sin signos radiológicos de malignidad. Se realizó una salpingo-ooforectomía unilateral con linfadenectomía pélvica y paraaórtica ipsilateral, por vía laparoscópica, tras confirmarse la presencia de células tumorales en la biopsia intraoperatoria. La evolución posterior de la paciente fue favorable.

Mortalidad y años de vida potenciales perdidos por enfermedades aterotrombóticas en el municipio Cerro / Mortality and years of potential life lost from atherothrombotic disease in Cerro municipality

Introducción: los datos de mortalidad son base para una amplia gama de indicadores de diversa complejidad. No solo representan las herramientas para evaluar el riesgo de muerte en una población y la repercusión de las enfermedades en la salud, sino también la gravedad de las enfermedades y la sobrevivencia experimentada por la población.Objetivo: estimar la mortalidad y los años de vida potenciales perdidos por enfermedades aterotrombóticas en el municipio Cerro.Métodos: se realizó un estudio observacional, descriptivo, retrospectivo de las defunciones por enfermedades aterotrombóticas en el municipio Cerro en el período comprendido entre el 2000 y el 2006 y se analizaron por edad, sexo, sitio y causa de defunción. Para el análisis estadístico se procedió al cálculo de las tasas brutas y tipificadas de mortalidad y por años de vida potenciales perdidos por mortalidad.Resultados: se observó una tendencia a la disminución de la mortalidad y un aumento en los años de vida potenciales perdidos a lo largo de este período. Se constató una mayor tasa de mortalidad y una mortalidad prematura en las mujeres de 65 años y más. Hubo un mayor porcentaje de fallecidos por aterotrombosis periférica dentro de una institución hospitalaria.Conclusiones: el municipio Cerro mostró una tendencia a la disminución de la mortalidad por enfermedades aterotrombóticas, y un aumento en los años de vida potenciales perdidos por esta causa, donde las mujeres de la tercera edad fueron las más afectadas(AU)

Introduction: mortality data are the pillars of a wide range of indicators of varying complexity; they do not only represent tools for evaluation of the risk of dying in a population and the impact of diseases on health but also the severity of diseases and the survival rate of that population.Objective: to estimate mortality and the years of potential life lost from atherothrombotic diseases in Cerro municipality.Methods: retrospective, descriptive and observational study was conducted on deaths occurred in Cerro municipality due to atherothrombotic diseases in the period of 2000 through 2006 and were analyzed by age, sex, location and causes. For the statistical analysis, the gross and typed mortality rates and the years of potential life lost rates were also estimated.Results: downward trend in mortality and upward trend in the years of potential life lost were observed in this period. The mortality rate and the premature mortality were higher in women aged 65 and over. The percentage of deaths from peripheral atherothrombotic disease in a hospital center was higher.Conclusions: Cerro municipality showed a downward trend in mortality from atherothrombotic disease but an upward trend in the years of potential life lost due to this cause, being the older women the most affected(AU)

Educación terapéutica en diabetes en pacientes con una primera amputación por pie diabético / Therapeutic education on diabetes for patients with first amputation caused by diabetic foot

Introducción: la educación diabetológica es la base del tratamiento para las personas con diabetes, la falta de conocimientos sobre la enfermedad favorece la aparición de complicaciones.Objetivos: identificar las principales causas que provocaron una primera amputación por pie diabético, describir el seguimiento ambulatorio de estos pacientes y explorar los conocimientos sobre su autocuidado.Métodos: estudio descriptivo, de corte transversal en 110 pacientes diabéticos hospitalizados en el Instituto Nacional de Angiología por pie diabético sometidos a una primera amputación. Se analizaron variables demográficas y de salud, así como las características del seguimiento ambulatorio, los conocimientos de los pacientes sobre la enfermedad y las principales causas de la lesión desencadenante.Resultados: la edad promedio fue de 61 años; y 15,4 años de evolución de la enfermedad. El 70,8 por ciento de los pacientes no tenían un seguimiento ambulatorio periódico, menos del 32 por ciento recibió cursos de educación diabetológica. Solo un tercio acudía periódicamente a los servicios de podología. Muy pocos pacientes pudieron expresar de forma precisa y concreta los cuidados de los pies. Entre las principales causas comentadas por los pacientes, que desencadenaron la lesión y que terminó en una primera amputación estuvieron "los pinchazos" y "el rebajar callosidades".Conclusiones: la mayoría de los diabéticos con una primera amputación no tenían un seguimiento periódico ni especializado para su enfermedad, insuficientes conocimientos sobre su autocuidado lo que probablemente generó que las conductas inapropiadas identificadas causaran una lesión complicada que requirió una amputación. Se impone la necesidad de un proceso educativo que sea eficiente para todas las personas con diabetes y así reducir las amputaciones(AU)

Introduction: diabetes education is the mainstay of treatment for people with diabetes since lack of knowledge about the disease favors the occurrence of complications.Objectives: to identify the main causes that led to a first diabetic foot amputation, to describe outpatient monitoring of these patients and to explore their knowledge about self diabetic foot care.Methods: descriptive and cross-sectional study conducted in 110 diabetic patients hospitalized at the National Institute of Angiology due to first diabetic foot amputation. The demographic and health variables as well as the characteristics of patient follow-up, patients' knowledge about the disease and the leading cause of the triggering injury were all taken into consideration.Results: it was found that the average age was 61 years, and 15.4 years of disease progression. In the study group, 70.8 percent of patients had no regular outpatient follow-up, less than 32 percent had received education courses on diabetes. Only one third of them came regularly to podiatric services. Very few patients were able to clearly say the aspects of foot care. The main causes stated by patients, which triggered the injury and led to a first amputation, were "punctures" and "reducing calluses".Conclusions: most diabetics with a first amputation did not have a either systematic or specialized monitoring for disease, with insufficient knowledge about self diabetic foot care, which probably led to identified inappropriate behaviors that caused complications and finally amputation. It is necessary to implement an effective educational process for all the diabetic persons and thus reduce amputations(AU)

Mortalidad y años de vida potenciales perdidos por enfermedades aterotrombóticas en el municipio Cerro / Mortality and years of potential life lost from atherothrombotic disease in Cerro municipality

Introducción: los datos de mortalidad son base para una amplia gama de indicadores de diversa complejidad. No solo representan las herramientas para evaluar el riesgo de muerte en una población y la repercusión de las enfermedades en la salud, sino también la gravedad de las enfermedades y la sobrevivencia experimentada por la población. Objetivo: estimar la mortalidad y los años de vida potenciales perdidos por enfermedades aterotrombóticas en el municipio Cerro. Métodos: se realizó un estudio observacional, descriptivo, retrospectivo de las defunciones por enfermedades aterotrombóticas en el municipio Cerro en el período comprendido entre el 2000 y el 2006 y se analizaron por edad, sexo, sitio y causa de defunción. Para el análisis estadístico se procedió al cálculo de las tasas brutas y tipificadas de mortalidad y por años de vida potenciales perdidos por mortalidad. Resultados: se observó una tendencia a la disminución de la mortalidad y un aumento en los años de vida potenciales perdidos a lo largo de este período. Se constató una mayor tasa de mortalidad y una mortalidad prematura en las mujeres de 65 años y más. Hubo un mayor porcentaje de fallecidos por aterotrombosis periférica dentro de una institución hospitalaria. Conclusiones: el municipio Cerro mostró una tendencia a la disminución de la mortalidad por enfermedades aterotrombóticas, y un aumento en los años de vida potenciales perdidos por esta causa, donde las mujeres de la tercera edad fueron las más afectadas(AU)

Introduction: mortality data are the pillars of a wide range of indicators of varying complexity; they do not only represent tools for evaluation of the risk of dying in a population and the impact of diseases on health but also the severity of diseases and the survival rate of that population. Objective: to estimate mortality and the years of potential life lost from atherothrombotic diseases in Cerro municipality. Methods: retrospective, descriptive and observational study was conducted on deaths occurred in Cerro municipality due to atherothrombotic diseases in the period of 2000 through 2006 and were analyzed by age, sex, location and causes. For the statistical analysis, the gross and typed mortality rates and the years of potential life lost rates were also estimated. Results: downward trend in mortality and upward trend in the years of potential life lost were observed in this period. The mortality rate and the premature mortality were higher in women aged 65 and over. The percentage of deaths from peripheral atherothrombotic disease in a hospital center was higher. Conclusions: Cerro municipality showed a downward trend in mortality from atherothrombotic disease but an upward trend in the years of potential life lost due to this cause, being the older women the most affected(AU)

Educación terapéutica en diabetes en pacientes con una primera amputación por pie diabético / Therapeutic education on diabetes for patients with first amputation caused by diabetic foot

Introducción: la educación diabetológica es la base del tratamiento para las personas con diabetes, la falta de conocimientos sobre la enfermedad favorece la aparición de complicaciones. Objetivos: identificar las principales causas que provocaron una primera amputación por pie diabético, describir el seguimiento ambulatorio de estos pacientes y explorar los conocimientos sobre su autocuidado. Métodos: estudio descriptivo, de corte transversal en 110 pacientes diabéticos hospitalizados en el Instituto Nacional de Angiología por pie diabético sometidos a una primera amputación. Se analizaron variables demográficas y de salud, así como las características del seguimiento ambulatorio, los conocimientos de los pacientes sobre la enfermedad y las principales causas de la lesión desencadenante. Resultados: la edad promedio fue de 61 años; y 15,4 años de evolución de la enfermedad. El 70,8 por ciento de los pacientes no tenían un seguimiento ambulatorio periódico, menos del 32 por ciento recibió cursos de educación diabetológica. Solo un tercio acudía periódicamente a los servicios de podología. Muy pocos pacientes pudieron expresar de forma precisa y concreta los cuidados de los pies. Entre las principales causas comentadas por los pacientes, que desencadenaron la lesión y que terminó en una primera amputación estuvieron "los pinchazos" y "el rebajar callosidades". Conclusiones: la mayoría de los diabéticos con una primera amputación no tenían un seguimiento periódico ni especializado para su enfermedad, insuficientes conocimientos sobre su autocuidado lo que probablemente generó que las conductas inapropiadas identificadas causaran una lesión complicada que requirió una amputación. Se impone la necesidad de un proceso educativo que sea eficiente para todas las personas con diabetes y así reducir las amputaciones(AU)

Introduction: diabetes education is the mainstay of treatment for people with diabetes since lack of knowledge about the disease favors the occurrence of complications. Objectives: to identify the main causes that led to a first diabetic foot amputation, to describe outpatient monitoring of these patients and to explore their knowledge about self diabetic foot care. Methods: descriptive and cross-sectional study conducted in 110 diabetic patients hospitalized at the National Institute of Angiology due to first diabetic foot amputation. The demographic and health variables as well as the characteristics of patient follow-up, patients' knowledge about the disease and the leading cause of the triggering injury were all taken into consideration. Results: it was found that the average age was 61 years, and 15.4 years of disease progression. In the study group, 70.8 percent of patients had no regular outpatient follow-up, less than 32 percent had received education courses on diabetes. Only one third of them came regularly to podiatric services. Very few patients were able to clearly say the aspects of foot care. The main causes stated by patients, which triggered the injury and led to a first amputation, were "punctures" and "reducing calluses". Conclusions: most diabetics with a first amputation did not have a either systematic or specialized monitoring for disease, with insufficient knowledge about self diabetic foot care, which probably led to identified inappropriate behaviors that caused complications and finally amputation. It is necessary to implement an effective educational process for all the diabetic persons and thus reduce amputations(AU)

The Influence of Dietary Fat Source on Life Span in Calorie Restricted Mice.

Calorie restriction (CR) without malnutrition extends life span in several animal models. It has been proposed that a decrease in the amount of polyunsaturated fatty acids (PUFAs), and especially n-3 fatty acids, in membrane phospholipids may contribute to life span extension with CR. Phospholipid PUFAs are sensitive to dietary fatty acid composition, and thus, the purpose of this study was to determine the influence of dietary lipids on life span in CR mice. C57BL/6J mice were assigned to four groups (a 5% CR control group and three 40% CR groups) and fed diets with soybean oil (high in n-6 PUFAs), fish oil (high in n-3 PUFAs), or lard (high in saturated and monounsaturated fatty acids) as the primary lipid source. Life span was increased (p < .05) in all CR groups compared to the Control mice. Life span was also increased (p < .05) in the CR lard mice compared to animals consuming either the CR fish or soybean oil diets. These results indicate that dietary lipid composition can influence life span in mice on CR, and suggest that a diet containing a low proportion of PUFAs and high proportion of monounsaturated and saturated fats may maximize life span in animals maintained on CR.

Mitochondrial ultrastructure and markers of dynamics in hepatocytes from aged, calorie restricted mice fed with different dietary fats.

In this paper we analyzed changes in hepatocyte mitochondrial mass and ultrastructure as well as in mitochondrial markers of fission/fusion and biogenesis in mice subjected to 40% calorie restriction (CR) for 18 months versus ad libitum-fed controls. Animals subjected to CR were separated into three groups with different dietary fats: soybean oil (also in controls), fish oil and lard. Therefore, the effect of the dietary fat under CR was studied as well. Our results show that CR induced changes in hepatocyte and mitochondrial size, in the volume fraction occupied by mitochondria, and in the number of mitochondria per hepatocyte. Also, mean number of mitochondrial cristae and lengths were significantly higher in all CR groups compared with controls. Finally, CR had no remarkable effects on the expression levels of fission and fusion protein markers. However, considerable differences in many of these parameters were found when comparing the CR groups, supporting the idea that dietary fat plays a relevant role in the modulation of CR effects in aged mice.

Artrogriposis: a propósito de un caso

El Síndrome de Artrogriposis incluye las deformidades músculo-esqueléticas que se originan en el período prenatal poco frecuente en la práctica médica, menos probable que se presente en articulaciones aisladas y no asociadas a otras malformaciones. Por la importancia del tema, se presenta un caso de recién nacida del sexo femenino con el Síndrome de Artrogriposis (AU)

Arthrogryposis Syndrome includes musculoskeletal deformities that originate in the prenatal period, it is rare in medical practice, less likely to be presented in isolated articulations and not associated with other malformations. Given the importance of the topic, a case of a newborn female with arthrogryposis syndrome is presented (AU)

Aspectos clínicos y epidemiológicos de los aneurismas de la aorta abdominal / Epidemiologic and clinical aspects of the abdominal aortic aneurysms

Introducción: el aneurisma de la aorta abdominal es una afección frecuente e importante en angiología , de ahí su valor clínico. Objetivo: describir algunos aspectos clínicos y epidemiológicos de los aneurismas de la aorta abdominal según sexo y tamaño del aneurisma. Métodos: estudio descriptivo longitudinal en 56 pacientes, mayores de 55 años, con el diagnóstico clínico y ultrasonográfico de aneurisma de la aorta abdominal. Se analizaron algunos aspectos clínicos y epidemiológicos. Se trabajó con las siguientes variables: edad, sexo, localización y tamaño del aneurisma, y factores de riesgo cardiovasculares. Resultados: se apreció una mayor frecuencia de aneurismas después de los 60 años en el sexo masculino, sobre todo en el grupo de edades entre 70 y 79 años (35,71 por ciento). Se encontró que el 32,14 por ciento de los pacientes eran asintomáticos, mientras que el tumor palpable (37,5 por ciento) y el dolor abdominal (19,64 por ciento) fueron los hallazgos clínicos más frecuentes. Se observó un predominio de hipertensión arterial (64,29 por ciento) y de tabaquismo (67,86 por ciento). El 56,5 por ciento de los pacientes con aneurismas grandes tenía dos factores de riesgo, pero aquellos con aneurismas muy pequeños (45,8 por ciento) presentaban un solo factor. Se encontró un predominio de los aneurismas de localización infrarrenal en 53 casos.Conclusiones: los aneurismas de la aorta abdominal predominaron en pacientes mayores de 60 años, sobre todo si son hipertensos y fumadores, factores importantes a tener en cuenta aunque el paciente sea asintomático(AU)

Introduction: the abdominal aortic aneurysm is a frequent and important illness of clinical value in angiology.Objective: to describe some clinical and epidemiological aspects of the abdominal aortic aneurysms according to sex and size of the aneurysm. Methods: longitudinal descriptive study of 56 patients aged over 55 years, with clinical and ultrasonographic diagnosis of abdominal aortic aneurysm. Some clinical and epidemiological aspects were analyzed. The following variables were used such as age, sex, location and size of aneurysm, and cardiovascular risk factors.Results: aneurysms were more frequent in males aged over 60 years, mainly in 70-79 years (n= 26, 35.71 percent). It was found that 32.14 percent of patients were asymptomatic, whereas the palpable tumor (37.5 percent) and abdominal pain (19.64 percent) were the most common findings. Hypertension (64.29 percent) and smoking (67.86 percent) predominated. The 56.5 percent of patients with big aneurysms presented with two factors, but those with very small aneurysms (45.8 percent) presented just one. It was observed that infrarenal aneurysms were predominant, with 53 cases.Conclusion: the abdominal aortic aneurysm predominated in patient older than 60 years, mainly if they are hypertensive and smoker, which are important factors to bear in mind in asymptomatic patients(AU)

Calorie restriction influences key metabolic enzyme activities and markers of oxidative damage in distinct mouse liver mitochondrial sub-populations.

AIMS: The purpose of the study was to establish if enzyme activities from key metabolic pathways and levels of markers of oxidative damage to proteins and lipids differed between distinct liver mitochondrial sub-populations, and which specific sub-populations contributed to these differences. MAIN METHODS: Male C57BL/6J mice were fed non-purified diet for one month then separated into two groups, control and calorie-restricted (CR). The two groups were fed semi-purified diet (AIN93G), with the CR group receiving 40% less calories than controls. After two months, enzyme activities and markers of oxidative damage in mitochondria were determined. KEY FINDINGS: In all mitochondrial sub-populations, enzyme activities and markers of oxidative damage, from control and CR groups, showed a pattern of M1>M3>M10. Higher acyl-CoA dehydrogenase (ß-oxidation) and ß-hydroxybutyrate dehydrogenase (ketogenesis) activities and lower carbonyl and TBARS levels were observed in M1 and M3 fractions from CR mice. ETC enzyme activities did not show a consistent pattern. In the Krebs cycle, citrate synthase and aconitase activities decreased while succinate dehydrogenase and malate dehydrogenase activities increased in the M1 mitochondria from the CR versus control mice. SIGNIFICANCE: CR does not produce uniform changes in enzyme activities or markers of oxidative damage in mitochondrial sub-populations, with changes occurring primarily in the heavy mitochondrial populations. Centrifugation at 10,000 g to isolate mitochondria likely dilutes the mitochondrial populations which show the greatest response to CR. Use of lower centrifugal force (3000 g or lower) may be beneficial for some studies.

Alterations of ultrastructural and fission/fusion markers in hepatocyte mitochondria from mice following calorie restriction with different dietary fats.

We analyzed ultrastructural changes and markers of fission/fusion in hepatocyte mitochondria from mice submitted to 40% calorie restriction (CR) for 6 months versus ad-libitum-fed controls. To study the effects of dietary fat under CR, animals were separated into three CR groups with soybean oil (also in controls), fish oil, and lard. CR induced differential changes in hepatocyte and mitochondrial size, in the volume fraction occupied by mitochondria, and in the number of mitochondria per hepatocyte. The number of cristae per mitochondrion was significantly higher in all CR groups compared with controls. Proteins related to mitochondrial fission (Fis1 and Drp1) increased with CR, but no changes were detected in proteins involved in mitochondrial fusion (Mfn1, Mfn2, and OPA1). Although many of these changes could be attributed to CR regardless of dietary fat, changing membrane lipid composition by different fat sources did modulate the effects of CR on hepatocyte mitochondria.

Epidemiología de la enfermedad tromboembólica venosa / Epidemiology of venous thromboembolic disease

Introducción: la enfermedad tromboembólica venosa es un proceso grave y potencialmente mortal.Objetivo: actualizar los datos epidemiológicos de la enfermedad tromboembólica venosa.Fuente de datos: para la obtención de la información se realizaron búsquedas en el registro de ensayos del Grupo Cochrane de Enfermedades Vasculares Periféricas y el Registro Cochrane Central de Ensayos Controlados (CENTRAL) en The Cochrane Library base de datos de Medline, que incluye búsquedas en MEDLINE, también se revisaron artículos publicados sobre el tema en diferentes páginas web. Resultados: la enfermedad tromboembólica venosa es la tercera causa de muerte cardiovascular luego de la cardiopatía isquémica y el stroke. No hay consenso acerca de si la incidencia de la enfermedad tromboembólica venosa varía con el sexo. La incidencia anual del tromboembolismo pulmonar en la población general se ha estimado entre 70 y 180 casos año por cada 100 000 habitantes, y aumenta con la edad. El tromboembolismo pulmonar es responsable del 5 al 10 por ciento de las muertes intrahospitalarias.Conclusiones: la enfermedad tromboembólica venosa es una enfermedad prevalente, con medidas eficaces para su prevención, de alta morbilidad y mortalidad, con una incidencia que no ha cambiado, frecuentemente asintomática y por lo tanto no sospechada(AU)

Introduction: venous thromboembolic disease is a severe and potentially deadly process. Objective: to update the epidemiological data on the venous thromboembolic disease.Methods: for the information collection, several searches were made in the trial registry of the Cochrane Group for Peripheral Vascular Diseases and in the Cochrane Central Register of Controlled Trials located in the Medline Cochrane Library database. Unrestricted Medline and on-line published articles in different websites were also included. Results: venous thromboembolic disease stands as the third cardiovascular-related cause of death followed by ischemic cardiopathy and stroke. No consensus appears to be reached in relation to gender-incidence impact. The annual incidence of pulmonary thromboembolism in the general population has been estimated from 70 to 180 cases a year per 100 000 inhabitants, with an age-related increase. The pulmonary thromboembolism is indeed responsible for 5-10 percent of in-hospital deceases. Conclusions: venous thromboembolic disease is a largely prevalent, disease with high morbimortality and unchanged incidence; it is frequently asymptomatic and hence, unsuspected. A set of efficacious preventive measures are available(AU)

Tabaquismo y enfermedad arterial periférica / Smoking and peripheral arterial disease

Objetivo: determinar el comportamiento del tabaquismo en los pacientes con enfermedad arterial periférica. Métodos: estudio descriptivo y transversal en 83 pacientes de ambos sexos, con en un rango de edad entre 30-99 años y realizado en el primer trimestre del 2012. Se emplearon las siguientes variables de interés: edad, sexo, intensidad de adicción, tiempo de exposición a la adicción y diagnósticos al ingreso. Resultados: hubo predominio de fumadores hombres en el grupo de edad entre 70-79 años. Se encontró que 42 (50,6 por ciento) pacientes tenían más de 20 años de exposición a la adicción. Fue en el sexo masculino donde se halló el mayor porcentaje de fumadores, con 35 (51,4 por ciento) enfermos dentro del grupo de intensidad severa; este mismo comportamiento se halló en las mujeres en el grupo clasificado como moderado con 25 (53,3 por ciento) pacientes. Se constató un predominio de mujeres y hombres con ateroesclerosis obliterante grado IV fumadores. Además, el tabaquismo estuvo presente en más hombres que mujeres con esta enfermedad en su grado IIb y en igual número de casos, entre mujeres y hombres con isquemia crítica. Conclusiones: el tabaquismo es el factor de riesgo prevenible y evitable que mayor repercusión tiene sobre el desarrollo de la enfermedad arterial periférica, incide en la calidad de vida del paciente con gran repercusión económico social(AU)

Objective: to determine the behaviour of smoking in patients with peripheral arterial disease.Methods: a descriptive and cross-sectional study of 83 patients of both sexes aged 30-39 years in the first quarter of 2012. The following variables were used: age, sex, intensity of addiction, exposure time to addiction and diagnoses on admission. Results: smoking men aged 70 to 79 years prevailed. It was found that 42 (50.6 percent) patients were exposed to addiction for over 20 years. Males exhibited the highest percentage of smokers; 35(51.4 percent) of them included in severe intensity group; the moderate intensity group in females had 25 patients (53.3 percent). There was predominance of smoking women and men with obliterating atherosclerosis grade IV. Additionally, smoking was present in more men than women with obliterating atherosclerosis grade IIb and in more women than men with critical ischemia (33.3 percent vs. 7.4 percent). Conclusion: smoking is a preventable and avoidable risk factor with the greatest effect on the development of the peripheral arterial disease; it has also an impact on the quality of life of the patient with large socioeconomic cost(AU)