The Evaluation of the Containment Efficacy of Semi-Rigid Isolators for Housing Cages of Laboratory Animals Infected With BSL-3 Agents.

Research animals models infected with Biosafety Level-3 (BSL-3) agents need to be housed in specialized biocontainment caging. Most of these specialized cages have input and exhaust that is high efficiency particulate air filtered and sealed to prevent escape of the BSL-3 agent. An alternative to the use of the above BSL-3 biocontainment caging is the use of a flexible film or modified semi-rigid plastic film isolator that has its own high efficiency particulate air-filtered input and exhaust and is sealed with respect to the animal room environment, thus preventing BSL-3 agent escape. Standard caging can be housed within such an isolator. Computational fluid dynamics was used to evaluate the integrity of modified semi-rigid isolators for containment of aerosolized BSL-3 agents. Three isolators were located inside an animal BSL-3 room to provide an extra tier of protection and to permit different infectious studies within the same room while reducing or eliminating the risk of cross-contamination. The isolators were sized to house caging for rabbits and smaller non-human primates such as marmosets, African greens, and macaques. Multiple case studies of failure scenarios were investigated, including isolator breaches through the plastic membrane seam separation and rips, and exhaust fan failure. Breaching the level of containment provided by the isolators required the improbable simultaneous event of a plastic membrane rip in addition to the rare malfunction of the back-up exhaust fans. Each isolator was equipped with 2 blower motors connected in parallel to a common exhaust plenum and a battery backup. Even with this rare double (simultaneous) event, the animal BSL-3 room air exhaust system was able to contain the few droplets released in the simulated computational fluid dynamics breach. The modified semi-rigid isolators with negative airflow proved safe and effective for aerosol studies using BSL-3 agents, even in the unlikely event of a breach in containment.

Pathogenic, but Not Nonpathogenic, Rickettsia spp. Evade Inflammasome-Dependent IL-1 Responses To Establish an Intracytosolic Replication Niche.

Rickettsia species (spp.) are strict obligate intracellular bacteria, some of which are pathogenic in their mammalian host, including humans. One critical feature of these stealthy group of pathogens is their ability to manipulate hostile cytosolic environments to their benefits. Although our understanding of Rickettsia cell biology and pathogenesis is evolving, the mechanisms by which pathogenic Rickettsia spp. evade host innate immune detection remain elusive. Here, we show that disease severity in wild-type (WT) C57BL/6J mice infected with Rickettsia typhi (the etiologic agent of murine typhus) and Rickettsia rickettsii (the etiologic agent of Rocky Mountain spotted fever), but not with the nonpathogenic species Rickettsia montanensis, correlated with levels of bacterial burden as detected in the spleens of mice, as well as the serum concentrations of proinflammatory cytokine interleukin-1α (IL-1α) and, to a lesser extent, IL-1ß. Antibody-mediated neutralization of IL-1α confirmed a key role in controlling mortality rates and bacterial burdens of rickettsia-infected WT mice. As macrophages are a primary source of both IL-1α and IL-1ß cytokines, we determined the mechanism of the antirickettsial activities using bone marrow-derived macrophages. We found that pathogenic R. typhi and R. rickettsii, but not nonpathogenic R. montanensis, eluded pro-IL-1α induction and benefited predominantly from the reduced IL-1α secretion, via a caspase-11-gasdermin D (Gsdmd)-dependent pathway, to facilitate intracytosolic replication. Adoptive transfer experiments identified that IL-1α secretion by macrophages was critical for controlling rickettsiosis in WT mice. In sum, we identified a previously unappreciated pathway by which pathogenic, unlike nonpathogenic, rickettsiae preferentially target the caspase-11-Gsdmd-IL-1α signaling axis in macrophages, thus supporting their replication within the host. IMPORTANCE Currently, no vaccines are available to prevent rickettsioses, while vector-borne rickettsial infections in humans are on the rise globally. In fact, the insufficient understanding of how pathogenic Rickettsia species circumvent host immune defense mechanisms has significantly hindered the development of more effective therapeutics. Here, we identified a previously unappreciated role for the caspase-11-Gsdmd-IL-1α signaling axis in limiting the replication of pathogenic R. rickettsia and R. typhi species in murine macrophages and wild-type (WT) C57BL/6J mice. Adoptive transfer studies further identified IL-1α-secreting macrophages as critical mediators in controlling rickettsial infection in WT mice. Collectively, these findings provide insight into the potential mechanism of how pathogenic, but not nonpathogenic, Rickettsia spp. benefit from a reduction in the caspase-11-Gsdmd-mediated release of IL-1α to support host colonization.

Chronic ingestion of (3R,3'R,6'R)-lutein and (3R,3'R)-zeaxanthin in the female rhesus macaque.

PURPOSE: To investigate how supplementation of the monkey's diet with high doses of lutein (L), zeaxanthin (Z), or a combination of the two affects the plasma levels and ocular tissue deposition of these carotenoids and their metabolites over time and to determine whether these high doses can cause ocular toxicity. METHODS: Eighteen female rhesus monkeys were divided into groups of control (n = 3 control), L-treated (n = 5, 9.34 mg lutein/kg and 0.66 mg zeaxanthin/kg), Z-treated (n = 5, 10 mg zeaxanthin/kg), and L/Z-treated (n = 5, lutein and zeaxanthin, each 0.5 mg/kg). After 12 months of daily supplementation, one control animal, two L-treated animals, two Z-treated animals, and all the L/Z-treated animals were killed. The rest of the monkeys were killed after an additional six months without supplementation. Plasma and ocular tissue carotenoid analyses, fundus photography, and retina histopathology were performed on the animals. RESULTS: Supplementation of monkeys with L and/or Z increased the mean plasma and ocular tissue concentrations of these carotenoids and their metabolites. The mean levels of L and Z in the retinas of the L- and Z-treated animals after 1 year increased significantly over baseline. High dose supplementation of monkeys with L or Z did not cause ocular toxicity and had no effect on biomarkers associated with kidney toxicity. CONCLUSIONS: The mean levels of L and Z in plasma and ocular tissues of the rhesus monkeys increase with supplementation and in most cases correlate with the levels of their metabolites. Supplementation of monkeys with L or Z at high doses, or their combination does not cause ocular toxicity.

Creencias de Estudiantes de Secundaria Españoles y Mexicanos sobre las Causas de la Obesidad / Beliefs of Spaniard and Mexican High School Students about the Causes of Obesity

Resumen: Se exploraron, a través de un cuestionario diseñado ex profeso, las creencias sobre las causas de la obesidad en una muestra de 142 estudiantes de segundo y tercer grados de secundaria (71 españoles y 71 mexicanos). El rango de edad de los participantes fue de 13 a 16 años (M = 14.02, DE = .846). Los participantes consideraron que la Voluntad y la Personalidad son las causas más importantes de la obesidad, X 2 (5, 142) = 265.353, p < .001, en tanto que los factores considerados menos importantes fueron Comida, Educación, Ejercicio y Genética. Dicha forma de conceptuar las causas de la obesidad parece dar pie a que los participantes responsabilicen a las personas obesas de su condición, t(141) = -13.740, p < .001. Por último, se discute cómo se articula las creencias sobre las causas de la obesidad y las actitudes mantenidas hacia las personas obesas.

Abstract: In order to explore the beliefs about the causes of obesity, one questionnaire designed on purpose were applied to a sample of 142 students of second and third grades of secondary school (71 Spaniard and 71 Mexican), with ages between 13 and 16 years (M = 14.02, SD = .846). Participants considered that Volition and Personality were the most important causes of obesity, X 2 (5, 142) = 265 353, p <.001, while Food, Education, Exercise and Genetics were the least important factors. This way of conceptualizing the causes of obesity seems to lead participants to blame obese people because of their condition, t(141) = 13,740, p <.001. Finally, we discuss how beliefs about the causes of obesity and attitudes held towards obese people are articulated.

A heterotopic primate model for facial composite tissue transplantation.

The purpose of this study was to develop a nonhuman primate model for heterotopic composite tissue facial transplantation in which to study the natural history of facial transplantation and evaluate immunosuppressive regimens.A composite oromandibular facial segment transplant based on the common carotid artery was evaluated. Flaps from 7 cynomolgus monkeys were transplanted to the groins of 7 recipients at the superficial femoral artery and vein. The immunosuppressive regimen consisted of thymoglobulin, rapamycin, and tacrolimus. Allograft survival ranged from 6 to 129 days. Histology performed in the long-term survivor at the time of necropsy revealed extensive inflammation and necrosis of the allograft skin; however, muscle and bone elements were viable, with minimal inflammation. This heterotopic facial transplantation model avoids the potential morbidity of mandibular resection and orthotopic facial transplantation. Our work also concurs with the work of other groups who found that the skin component is the most antigenic.

DNA transfection of macaque and murine respiratory tissue is greatly enhanced by use of a nuclease inhibitor.

BACKGROUND: Nuclease activity present within respiratory tissues contributes to the rapid clearance of injected DNA and therefore may reduce the transfection activity of directly injected transgenes. Most gene transfer technologies transduce or transfect murine tissues more efficiently than corresponding primate tissues. Therefore, it is prudent to assess the utility of novel gene transfer strategies in both rodent and primate models before proceeding with further development. METHODS: This study analyzed the effects of ATA (a nuclease inhibitor) on the direct transfection of macaque and murine lung tissue; compared the levels of DNase activity in murine, primate, and human lung fluids; and tested the inhibitory activity of ATA on the DNase activity present in these samples. Fluorescent microspheres were used to detect areas of transfection in lung. RESULTS: Intratracheal administration of a nuclease inhibitor (ATA) with naked DNA (0.5 microg ATA/g body weight) enhanced direct transfection efficacy in macaque lung by over 86-fold and by over 54-fold in mouse lung. Hematoxylin and eosin staining showed no apparent tissue toxicity. Moreover, macaque, human, and mouse lung fluids were found to possess similar levels of DNase activity and this activity was inhibited by similar concentrations of ATA. The authors also successfully pioneered the use of carboxylate-modified microsphere tracers to identify areas of transfection and/or treatment. CONCLUSION: This work provides evidence that using direct nuclease inhibitors will enhance lung transfection and that nuclease activity is present in all lung fluids tested, which can be inhibited by the use of direct DNase inhibitors.

La depresión en el adulto mayor: algunas consideraciones para su diagnóstico en la atención primaria / Depression in elder adults: some considerations for its diagnosis in primary health care

El presente trabajo va dirigido a los médicos de Atención Primaria de Salud. Tiene en su contenido una breve reseña de los cambios que se producen en el envejecimiento desde el punto de vista orgánico, psicológico y social que predisponen a la aparición de la depresión en el adulto mayor. Se exponen las principales características, los criterios diagnósticos y las diferentes formas de presentación de la depresión según la Clasificación Internacional de Enfermedades en su Versión #-10. Se orientan las acciones para llegar al diagnóstico como: confección de la historia clínica, examen físico, indicación de complementarios más importantes y los principales diagnósticos diferenciales a tener en cuenta. Este trabajo tiene el propósito de incrementar los conocimientos para perfeccionar actitudes y desarrollar buenas prácticas en la prevención, diagnóstico precoz, tratamiento y rehabilitación psicosocial de la depresión en el Adulto Mayor...(AU)

The current work is directed to the physicians of the Primary Health Care. It contents a short review on the changes that take place during aging form the organic, psychological and social point of view, predisposing depression emergency in elder adults. We expose the main characteristics, the diagnostic criteria and different forms of depression emergency according to the International Classification of Diseases Version # 10. We orient actions to arrive to a diagnosis: confection of the clinical review, physical examination, indication of the most important complementary examinations and the main differential diagnosis to take into account. The purpose of this work is increasing knowledge to improve attitudes and develop new practices preventing, precociously diagnosing, treating and psychosocial rehabilitation of depression in elder adults

La depresión en el adulto mayor: algunas consideraciones para su diagnóstico en la atención primaria / Depression in elder adults: some considerations for its diagnosis in primary health care

El presente trabajo va dirigido a los médicos de Atención Primaria de Salud. Tiene en su contenido una breve reseña de los cambios que se producen en el envejecimiento desde el punto de vista orgánico, psicológico y social que predisponen a la aparición de la depresión en el adulto mayor. Se exponen las principales características, los criterios diagnósticos y las diferentes formas de presentación de la depresión según la Clasificación Internacional de Enfermedades en su Versión #-10. Se orientan las acciones para llegar al diagnóstico como: confección de la historia clínica, examen físico, indicación de complementarios más importantes y los principales diagnósticos diferenciales a tener en cuenta. Este trabajo tiene el propósito de incrementar los conocimientos para perfeccionar actitudes y desarrollar buenas prácticas en la prevención, diagnóstico precoz, tratamiento y rehabilitación psicosocial de la depresión en el Adulto Mayor...

The current work is directed to the physicians of the Primary Health Care. It contents a short review on the changes that take place during aging form the organic, psychological and social point of view, predisposing depression emergency in elder adults. We expose the main characteristics, the diagnostic criteria and different forms of depression emergency according to the International Classification of Diseases Version # 10. We orient actions to arrive to a diagnosis: confection of the clinical review, physical examination, indication of the most important complementary examinations and the main differential diagnosis to take into account. The purpose of this work is increasing knowledge to improve attitudes and develop new practices preventing, precociously diagnosing, treating and psychosocial rehabilitation of depression in elder adults.

Tumores del soma, 1981-1987 / Tumors of soma, 1981-1987

Se revisaron 323 historias clínicas de pacientes con afección tumoral, que fueron atendidos en el Servicio de Ortopedia del Hospital "Dr. Ernesto Guevara de la Serna" en el período comprendido entre 1981 y 1987, con el objetivo de conocer aspectos generales como edad, sexo y especificamente tipo de tumores, localización, síntoma inicial, tiempo transcurrido entre consulta, diagnóstico, etcetera

Tumores del soma, 1981-1987 / Tumors of soma, 1981-1987

Se revisaron 323 historias clínicas de pacientes con afección tumoral, que fueron atendidos en el Servicio de Ortopedia del Hospital "Dr. Ernesto Guevara de la Serna" en el período comprendido entre 1981 y 1987, con el objetivo de conocer aspectos generales como edad, sexo y especificamente tipo de tumores, localización, síntoma inicial, tiempo transcurrido entre consulta, diagnóstico, etcetera (AU)