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Introduction. As a result of the COVID-19 pandemic, the prevalence of stress, anxiety, depression, and alcohol consumption has increased among medical students. Mindfulness is an intervention to decrease these psychopathologies and alcohol consumption; however, evidence has shown unclear results regarding its efficacy. Objective. To evaluate the effectiveness of an online Mindfulness-based intervention (MBI) on stress, anxiety, and depression symptomatology levels, as well as on alcohol consumption and mindfulness status in medical students during the COVID-19 pandemic. Method. A quasi-experimental study was conducted on 237 students, obtaining sociodemographic data. In addition the levels of psychopathology, alcohol consumption, and state of mindfulness: were measured pre-and post-intervention through the DASS-21, AUDIT, and MASS instruments. Eight online Mindfulness sessions were conducted once a week for approximately one hour each. Results. MBI did not reduce levels of psychopathologies or alcohol consumption, nor did the mindfulness status improve. High levels of psychopathologies, dropout rate, and lack of voluntary participation were the main factors limiting the effectiveness of the online MBI. Discussion and conclusion. The online MBI wasn’t effective among the population under study: we recommend generation strategies where students are involved in and complete intervention programs. Results from this research will help enhance future online mindfulness interventions.

La reactancia psicológica es una reacción negativa instintiva en respuesta a la imposición a un qué hacer; en estudios previos identificamos poca participación de los estudiantes en intervenciones y se desconoce su relación con la reactancia. Objetivo: Conocer el nivel de reactancia de los estudiantes, así como su asociación con la percepción y participación en una intervención psicológica, factores sociodemográficos y la sintomatología de ansiedad durante la pandemia. Métodos: Se realizó un estudio descriptivo, analítico, transversal en estudiantes de medicina, a través de un formulario de Google se utilizaron la escala de reactancia de Hong, el Inventario de ansiedad rasgo y estado (AR y AE), y un cuestionario sociodemográfico básico. Resultados: Alrededor del 43 % de los estudiantes tienen niveles medios y altos de reactancia, se observó mayor reactancia en los estudiantes de menor edad, de semestres inferiores, con conocimiento de presentar sintomatología de ansiedad, conscientes de necesitar ayuda y considerar importante las intervenciones. Por otro lado, cerca de 70 % de los estudiantes muestran niveles medios a muy altos de AE, y cerca del 40 % mostró niveles medios-altos de AR. No se observó asociación entre la reactancia, la participación en la intervención, y los mayores niveles de ansiedad. Conclusión: La reactancia modifica la percepción y búsqueda de apoyo por medio de las intervenciones psicológicas, es necesario establecer un cambio de actitudes en los universitarios por medio de técnicas psicológicas para mitigar la evasión de responsabilidades de autocuidado, principalmente en los individuos altamente reactivos.

Objetivo: El presente estudio pretende determinar la asociación y factores implicados entre haber padecido un evento de COVID-19 con el desarrollo de un evento cerebrovascular. Métodos: Es un estudio observacional, de casos y controles, analítico, retrospectivo, con relación 1:2. Aplicado en la población del servicio de Urgencias, Medicina interna y Medicina familiar, del Hospital General de Zona con Medicina Familiar N° 32 de Minatitlán Veracruz. Resultados: Se obtuvo una muestra final de 111 casos y 222 controles. El promedio de edad es de 58 años ±17.6. Del total de pacientes 126 (37.8%) son hombres y 207 (62.2%) son mujeres. 159 pacientes (47.74%) tuvieron antecedente positivo de COVID-19. Se encontró un Odds Ratio de 1.38 (95%; 0.876 – 2.186). La edad de los pacientes, la gravedad de la infección en su fase aguda, el nivel de gravedad del evento cerebrovascular y el antecedente de vacuna, fueron resultados estadísticamente significativos. Conclusión: El COVID-19 se encuentra asociado como factor independiente al desarrollo de evento cerebrovascular.

Due to the high demands of the medicine career, coupled with students' work and personal obligations, they are a susceptible population to develop anxiety and Burnout syndrome (BS) which can influence their academic performance. The aim of the present study was to determine the prevalence and symptomatology of anxiety and Burnout, as well as to identify their impact on the academic performance of students at the end of their medical degree.A cross-sectional, observational study was conducted on medical students at the end of their degree, using the Trait and State Anxiety inventory, the Maslach Burnout scale, and the grade point average through the Academic Secretary. Results: A prevalence of state anxiety (SA) of 40. 6% and trait anxiety (TA) of 31. 2% was observed, both with similar proportions between a medium and high level (75-25%), with an association between them. The prevalence of BS was 15. 6%, of which 17. 2% and 23. 4% respectively showed high levels of fatigue and depersonalization, moreover, 18. 8% showed low levels of personal fulfillment.At the end of the career, students show symptoms of SA and TA with a high association between them. Therefore, it is important to emphasize that transitory anxiety can become part of an anxious response as a personality trait. The prevalence of BS was low and not related to academic performance, age, or sex.Las altas exigencias que presenta la carrera de medicina, aunado a las obligaciones laborales y personales de los estudiantes, los predispone a desarrollar ansiedad y síndrome de Burnout (SB), lo cual puede influir en su rendimiento académico. El objetivo del presente estudio fue determinar la prevalencia y la sintomatología de ansiedad y Burnout, así como identificar su impacto en el rendimiento académico de los estudiantes al término de la licenciatura en médico cirujano.Se realizó un estudio transversal, observacional en estudiantes de medicina al término de la carrera, se utilizó el inventario de Ansiedad Rasgo y Estado, la escala Maslach Burnout y el promedio de las calificaciones a través de la Secretaria Académica.Se observó una prevalencia de ansiedad estado (AE) y rasgo (AR) de 40.6% y 31.2% respectivamente, ambas con proporciones similares entre nivel medio (75%) y alto (25%), y con asociación entre las mismas. La prevalencia del SB fue de 15.6%, de los cuales 17.2 y 23.4% presentaron niveles altos de cansancio y de despersonalización respectivamente, además 18.8% mostró niveles bajos de realización personal.Al término de la licenciatura los estudiantes muestran sintomatología de AR y AE con alta asociación entre ambas, por lo que es importante resaltar que la ansiedad transitoria puede llegar a integrar una respuesta ansiosa como rasgo de su personalidad. La prevalencia de SB fue baja y sin relación con el rendimiento académico, la edad o el sexo.

As the U.S. health care system changes and technology alters how doctors work and learn, medical schools and their faculty are compelled to modify their curricula and teaching methods. In this article, educational leaders and key faculty describe how the Pathways curriculum was conceived, designed, and implemented at Harvard Medical School. Faculty were committed to the principle that educators should focus on how students learn and their ability to apply what they learn in the evaluation and care of patients. Using the best evidence from the cognitive sciences about adult learning, they made major changes in the pedagogical approach employed in the classroom and clinic. The curriculum was built upon 4 foundational principles: to enhance critical thinking and provide developmentally appropriate content; to ensure both horizontal integration between courses and vertical integration between phases of the curriculum; to engage learners, foster curiosity, and reinforce the importance of student ownership and responsibility for their learning; and to support students' transformation to a professional dedicated to the care of their patients and to their obligations for lifelong, self-directed learning.The practice of medicine is rapidly evolving and will undoubtedly change in multiple ways over the career of a physician. By emphasizing personal responsibility, professionalism, and thinking skills over content transfer, the authors believe this curriculum will prepare students not only for the first day of practice but also for an uncertain future in the biological sciences, health and disease, and the nation's health care system, which they will encounter in the decades to come.

The Mixton War (1540–1541) was the last symmetric war within the viceroyalty of New Spain until the arrival of the insurgency and the Mexican Independence War in the early 19th century. In this paper, I approach, from military history, those aspects corresponding to the military strategy carried out by both sides in order to understand the decisions that were made, the reason for them and how these led to the defeat of the indigenous army at the end of 1541.

Autism spectrum disorder is associated with alterations in GABAergic and glutamatergic neurotransmission. Here, we aimed to determine the concentration of GABA, glutamate, glutamine, aspartate, taurine, and glycine in brain tissue and plasma of rats prenatally exposed to valproic acid (VPA), a well-characterized experimental model of autism. Pregnant rats were injected with VPA (600mg/Kg) during the twelfth-embryonic-day. Control rats were injected with saline. On the fourteen-postnatal-day, rats from both groups (males and females) were anesthetized, euthanized by decapitation and their brain dissected out. The frontal cortex, hippocampus, amygdala, brain stem and cerebellum were dissected and homogenized. Homogenates were centrifuged and supernatants were used to quantify amino acid concentrations by HPLC coupled with fluorometric detection. Blood samples were obtained by a cardiac puncture; plasma was separated and deproteinized to quantify amino acid concentration by HPLC. We found that, in VPA rats, glutamate and glutamine concentrations were increased in hippocampus and glycine concentration was increased in cortex. We did not find changes in other regions or in plasma amino acid concentration in the VPA group with respect to control group. Our results suggest that VPA exposure in utero may impair inhibitory and excitatory amino acid transmission in the infant brain.

En México como en el resto de Latinoamérica nuestros hábitos alimenticiosnutricionales, culturales y educación favorecen a los factores de riesgo para desarrollar padecer diversas enfermedades crónicas degenerativas como la diabetes, hipertensión arterial, obesidad o trastornos como el aumento de colesterol y triglicérido. Cuando tres o más de los anteriores factores se presentan en conjunto proporcionan lo que conocemos como síndrome metabólico. El objetivo de este estudio fue determinar la prevalencia del síndrome metabólico de estudiantes con factores de riesgo para desarrollarlo en estudiantes universitarios. El estudio se realizó a estudiantes de primer año de la Universidad Veracruzana Campus Minatitlán, tomando en cuenta los resultados del Examen de Salud Integral que se les aplico al ingresar a la universidad, además se les realizó una prueba rápida de glucosa, somatometría y un cuestionario sociodemografico. Se estudió una población de 91 estudiantes de las facultades de Medicina, Odontología y Trabajo social de los cuales 73,6 % eran mujeres y 26,4 % hombres, en una edad promedio de 19.2 ± 1.1 años, encontrando una prevalencia de 6,6 % de síndrome metabólico. Además se observó que 37,4 % presentaron un factor de riesgo, 12 % dos factores de riesgo y 44 % no mostraron ningún factor de riesgo. Siendo el principal factor de riesgo la obesidad presente en 44 % de los estudiantes, seguido de las hipertrigliceridemias. La prevalencia de síndrome metabólico en los estudiantes de nuevo ingreso de la facultad de medicina del campus Minatitlán es alta con respecto a los reportes nacionales e internaciones, en donde más del 50 % presenta algún factor de riesgo, siendo la obesidad el principal con un mayor predominio en las mujeres.

Introduction In a flipped classroom, students learn basic concepts before class, allowing them time during class to apply newly gained knowledge to problem sets and cases. Harvard Medical School (HMS) has introduced a form of flipped classroom, called case-based collaborative learning (CBCL), during preclinical curricula. Finding few published resources, the HMS Academy's Peer Observation of Teaching Interest Group developed a guide for observations and feedback to CBCL facilitators. Methods After conducting an extensive literature search, speaking to flipped classroom methodology experts, and observing 14 facilitators using CBCL methods, the interest group identified specific teaching behaviors that optimize student interaction and knowledge application. The group next engaged in several rounds of the modified Delphi method to develop the CBCL peer observation worksheet and compendium and then tested these materials' effectiveness in capturing CBCL teaching behaviors and providing feedback to CBCL faculty facilitators. Results Seventy-three percent of faculty rated the worksheet and compendium as extremely helpful or helpful in identifying new teaching techniques. Moreover, 90% found the CBCL peer observation and debriefing to be extremely helpful or helpful, and 90% were extremely likely or likely to incorporate peer suggestions in future teaching sessions. Discussion Medical schools have begun to embrace flipped classroom methods to eliminate passive, lecture-style instruction during the preclinical years of the MD curriculum. This tool identifies specific in-classroom approaches that engage students in active learning, guides peer observers in offering targeted feedback to faculty on teaching strategies, and presents consensus-based resources for use during CBCL faculty development and training.

It is essential to document habitat occupancy patterns and population structure to facilitate the survival of primates in areas of anthropogenic disturbance. The overlapping of the Nearctic and Neotropical regions in the Olmec region of Mexico make this area particularly important as part of a natural biological corridor that harbors a high number of endemic species and connects the Atlantic and Pacific coastal plains. We surveyed Alouatta palliata mexicana (Mexican mantled howlers) in a 300-km2 area to determine if fragment occupation and subpopulation structure were related to the spatial attributes of the fragments. We measured the fragment size and shape as well as the distances to the nearest road, human settlement, agricultural field, and nearest neighboring fragment. During 1 year (ca. 4500 fieldwork hours) we surveyed 48 fragments, 17 of which were occupied, and counted 198 howlers. Larger fragments that were farther from agricultural activities were more likely to be occupied. Subpopulation size and number of individuals in all age–sex classes increased in larger fragments that were closer to other fragments. We found more females and juveniles, as well as more females per male in fragments that were farther from roads and we found fewer immatures per female, females per male, and individuals per area in more irregular fragments. In addition, more males and immatures per female occurred in fragments that were farther from agricultural fields. The Olmec Region is located at the center of the geographic distribution of mantled howlers in Mexico, and could therefore play a fundamental role in maintaining the contact between different populations. However, our study suggests that mantled howlers are highly threatened by anthropogenic habitat disturbance in this area, mainly through the loss of their habitat and contact with humans.

Objetivo: evaluar el patrón de consumo y las percepciones sobre el uso de alcohol por personas cercanas a los estudiantes. Método: se trata de un estudio del tipo transversal y de abordaje cuantitativo, involucrando 940 estudiantes de seis planteles del Colegio de Bachilleres del Estado de Veracruz, México. Resultados: las prevalencias del uso fueron: 57.4% en la vida, 31.5% en último año, 25.3% en el último mes; 7.4 % consumen en nivel problemático del alcohol. Las percepciones negativas sobre el consumo de alcohol fueron evaluadas por padres y madres, predominantemente entre los estudiantes que consumen en bajo riesgo. Conclusión: el consumo de alcohol entre los estudiantes de bachillerato es común, principalmente entre los hombres, con un patrón de inicio es cada vez más precoz, y con la incidencia de intoxicación. Además, estas siempre muy presente en los estudiantes con problemas en las relaciones parentales. Los resultados podrán subsidiar la planificación de programas preventivos en relación al consumo de alcohol en el ámbito escolar.

Objetivo: Identificar el estado de ánimo y su relación con el rendimiento académico en los estudiantes de la Facultad de Medicina. Metodología: Se llevó a cabo un estudio de tipo observacional, descriptivo, transversal y de corte cuantitativo en estudiantes de segundo semestre de la Facultad de Medicina del campus Minatitlán de la Universidad Veracruzana, México, a los cuales se les aplicó un cuestionario para variables sociodemográficas y otro para medir el nivel de depresión diseñado por el Dr. Guillermo Calderón Narváez, con previo consentimiento informado. Resultados: Se encuestaron 64 estudiantes de los cuales 51.6 % fueron mujeres y 48.4% hombres, con un promedio de edad de 19 ± 1.19 años (rango de 18 a 26). En relación al nivel de depresión se encontró que 81.3% son normales, 15.6% presentó reacción de ansiedad y 3.1% depresión moderada. Con respecto a las calificaciones se observó que 6.3% de los estudiantes presentaron calificaciones regulares, 64.1% buenas y 29.7% excelentes. No encontramos relación entre el nivel de depresión y el rendimiento académico (X2= 0.618, p=0.961). Sin embargo, se evidenció que la presencia de síntomas depresivos es más alta en los estudiantes de mayor edad y que tienen problemas familiares. Adicionalmente se observó que 15% de la población presenta ansiedad. Conclusión. No se encontró relación entre el nivel de depresión y el rendimiento académico en los estudiantes de segundo semestre de medicina del campus Minatitlán, posiblemente se debe a que la mayoría de los estudiantes tienen calificaciones buenas y excelentes.

Background Medicine subspecialty consultation is becoming increasingly important in inpatient medicine. Objective We conducted a survey study in which we examined hospitalist practices and attitudes regarding medicine subspecialty consultation. Design and setting The survey instrument was developed by the authors based on prior literature and administered online anonymously to hospitalists at 4 academic medical centers in the United States. Measurements The survey evaluated 4 domains: (1) current consultation practices, (2) preferences regarding consultation, (3) barriers to and facilitating factors of effective consultation, and (4) a comparison between hospitalist-fellow and hospitalist-subspecialty attending interactions. Results One hundred twenty-two of 261 hospitalists (46.7%) responded. The majority of hospitalists interacted with fellows during consultation. Of those, 90.9% reported that in-person communication occurred during less than half of consultations, and 64.4% perceived pushback at least "sometimes " in their consult interactions. Participants viewed consultation as an important learning experience, preferred direct communication with the consulting service, and were interested in more teaching during consultation. The survey identified a number of barriers to and facilitating factors of an effective hospitalist-consultant interaction, which impacted both hospitalist learning and patient care. Hospitalists reported more positive experiences when interacting with subspecialty attendings compared to fellows with regard to multiple aspects of the consultation. Conclusion The hospitalist-consultant interaction is viewed as important for both hospitalist learning and patient care. Multiple barriers and facilitating factors impact the interaction, many of which are amenable to intervention.

A 63-year-old man with a history of type 2 diabetes presented with hip and shoulder pain in June 2010. He was on atorvastatin 80 mg daily and his creatine kinase (CK) was mildly elevated, so he was switched to simvastatin 20 mg daily. Three months later, he was referred to a rheumatologist. His CK was 142 U/L and his erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were mildly elevated (28 mm/hour and 14 mg/L, respectively). He was diagnosed with polymyalgia rheumatica. He was started on a methylprednisolone taper starting at 16 mg going to 8 mg daily with mild, although transient, improvement. He remained on 8 mg daily methylprednisolone for several months. Eight months later, he began to notice progressive proximal leg weakness and difficulty climbing stairs. His serum CK was 1,600 U/L. He stopped the simvastatin and was started on gemfibrozil. An EMG was normal. His CK rose to the 3,000s IU/L 3 months later. Nine months later, 8-day methylprednisolone tapers starting at 16 mg daily were symptomatically ineffective, as was a prednisone 60 mg daily tapered over 2 weeks.

Para tratar de asignarle un contenido a la frase que titula el tema que debemos tratar en esta mesa redonda, el cual nos permita iniciar su analisis, debemos recordar que, gramaticalmente, el vocablo responsabilidad significa Cualidad de responsable , o sea, Obligado a responder de algo o por alguien, y en una segunda acepcion, Deuda, obligacion de reparar y satisfacer, por si o por otra persona, a consecuencia de un delito, de una culpa o de otra causa legal ; tambien quiere decir Cargo u obligacion moral que resulta para alguien del posible yerro en cosa o asunto determinado y, en el campo del derecho, se identifica como la Capacidad existente en todo sujeto activo de derecho para reconocer y aceptar las consecuencias de un hecho realizado libremente ; por su parte, el adjetivo social indica Perteneciente o relativo a la sociedad .

A 29-year-old man was admitted to the hospital because of anemia, jaundice, fatigue, and diffuse body aches. He had returned from a 3-month trip to North Africa 1 month before presentation. A diagnostic test was performed.

Background Epidemiological evidence indicates epilepsy is more common in patients with autism spectrum disorders (ASD) (20–25%) than in the general population. The aim of this project was to analyze seizure susceptibility in developing rats prenatally exposed to valproic acid (VPA) as autism model. Methods Pregnant females were injected with VPA during the twelfth embryonic day. Seizures were induced in fourteen-days-old rat pups using two models of convulsions: pentylenetetrazole (PTZ) and lithium-pilocarpine (Li-Pilo). Results Two subgroups with different PTZ-induced seizure susceptibility in rats exposed to VPA were found: a high susceptibility (VPA+) (28/42, seizure severity 5) and a low susceptibility (VPA−) (14/42, seizure severity 2). The VPA+ subgroup exhibited an increased duration of the generalized tonic-clonic seizure (GTCS; 45 ± 2.7 min), a higher number of rats showed several GTCS (14/28) and developed status epilepticus (SE) after PTZ injection (19/27) compared with control animals (36.6 ± 1.9 min; 10/39; 15/39, respectively). No differences in seizure severity, latency or duration of SE induced by Li-Pilo were detected between VPA and control animals. Discussion Prenatal VPA modifies the susceptibility to PTZ-induced seizures in developing rats, which may be linked to an alteration in the GABAergic transmission. These findings contribute to a better understanding of the comorbidity between autism and epilepsy.

A 62-year-old man was admitted to this hospital because of paresthesias, weight loss, jaundice, and anemia. Diagnostic test results were received.

Multiple autoimmune diseases are characterized by the involvement of autoreactive Abs in pathogenesis. Problems associated with existing therapeutics such as the delivery of intravenous immunoglobulin have led to interest in developing alternative approaches using recombinant or synthetic methods. Toward this aim, in the current study, we demonstrate that the use of Fc-engineered Abs (Abs that enhance IgG degradation [Abdegs]) to block neonatal FcR (FcRn) through high-affinity, Fc region binding is an effective strategy for the treatment of Ab-mediated disease. Specifically, Abdegs can be used at low, single doses to treat disease in the K/B×N serum transfer model of arthritis using BALB/c mice as recipients. Similar therapeutic effects are induced by 25- to 50-fold higher doses of i.v. Ig. Importantly, we show that FcRn blockade is a primary contributing factor toward the observed reduction in disease severity. The levels of albumin, which is also recycled by FcRn, are not affected by Abdeg delivery. Consequently, Abdegs do not alter FcRn expression levels or subcellular trafficking behavior. The engineering of Ab Fc regions to generate potent FcRn blockers therefore holds promise for the therapy of Ab-mediated autoimmunity.

Liver transplant remains the ultimate treatment for decompensated liver disease. However, many diseases do recur after orthotopic liver transplant, which may affect recipients' quality of life and survival rate. We performed a systematic review of relevant epidemiological studies available on Medline that provided information on the recurrence of non-viral hepatitis after orthotopic liver transplantation in adult patients published until August 2010. All data were compiled from either review articles or retrospective studies. Primary sclerosing cholangitis, primary biliary cirrhosis, autoimmune hepatitis, non-alcoholic steatohepatitis, alcoholic steatohepatitis and haemochromatosis can recur after liver transplantation. The rates for disease recurrence varied according to the indication for transplantation, and ranged from 7 to 50%. Although the survival rate of patients with liver disease has increased with the advent of liver transplantation and novel immunosuppressive protocols, recurrence of the primary liver disease remains a concern. The recurrence rates differ not only according to the cause of underlying liver disease but also vary within the indication for transplant. Further studies are needed to elucidate the risk factors for varied disease recurrence.

Los planes y programas de educación física constituyen en nuestro país el conjunto de actividades físicas que, proyectadas con un criterio eminentemente educativo, se imparten a todos los niños, adolescentes y jóvenes, con carácter obligatorio, desde la etapa pre-escotar hasta el segundo año de la educación superior.Los objetivos y tareas de los planes de estudio contribuyen a aclarar más la idea de que la enseñanza de la educación física debe preparar a la juventud física y moralmente para poder complementar las diversas exigencias sociales. Los planes de estudio se concentran por las razones mencionadas en la formación física básica. Esta abarca la formación integral de las propiedades físicas, las capacidades y habilidades motrices, así como la formación de cualidades de la personalidad.

The contribution of Interleukin-1β (IL-1β) to neuronal injury induced by status epilepticus (SE) in the immature brain remains unclear. The goal of this study was to determine the hippocampal expression of IL-1β and its type 1 receptor (IL-1RI) following SE induced by the lithium-pilocarpine model in fourteen-days-old rat pups; control animals were given an equal volume of saline instead of the convulsant. IL-1β and IL-1RI mRNA hippocampal levels were assessed by qRT-PCR 6 and 24 h after SE or control conditions. IL-1β and IL-1RI expression was detected in the dorsal hippocampus by immunohistochemical procedures; Fluoro-Jade B staining was carried out in parallel sections in order to detect neuronal cell death. IL-1β mRNA expression was increased 6 h following SE, but not at 24 h; however IL-1RI mRNA expression was unaffected when comparing with the control group. IL-1β and IL-1RI immunoreactivity was not detected in control animals. IL-1β and IL-1RI were expressed in the CA1 pyramidal layer, the dentate gyrus granular layer and the hilus 6 h after SE, whereas injured cells were detected 24 h following seizures. Early expression of IL-1β and IL-1RI in the hippocampus could be associated with SE-induced neuronal cell death mechanisms in the developing rat. A contribuição de Interleucina-1β (IL-1β) para a lesão neuronal induzida pelo estado epiléptico (SE) no cérebro imaturo ainda permanece obscuro. O objetivo deste estudo foi determinar a expressão do hipocampo de IL-1β e seu receptor tipo 1 (IL-1RI) após SE induzido pelo modelo de lítio-pilocarpina em ratos com quatorze dias de idade; animais controle receberam um volume igual de soro fisiológico em vez do agente convulsivo. Níveis de hipocampo de IL-1β e IL-1RI foram avaliados por qRT-PCR 6 e 24 h após a condições SE ou de controlo. A expressão IL-1β mRNA e expressão de IL-1RI foi detectada no hipocampo dorsal, através de procedimentos de imuno-histoquímica. A expressão IL-1β de mRNA foi aumentada 6 h após a SE, mas não para as 24 h; no entanto a expressão de IL-1RI de ARNm não foi afetada quando comparada com o grupo controle. A imunorreatividade de IL-1β e IL-1RI não foi detectada em animais usados como controle. IL-1β e IL-1RI foram expressos na camada piramidal CA1, a camada granular após 6 h do estado epiléptico, enquanto que as células lesadas eram detectadas 24 h após as convulsões. A expressão precoce de IL-1β e IL-1RI no hipocampo pode ser associada com os mecanismos de morte celular neuronal induzida pelo SE com ratos em desenvolvimento.

Objectives The subspecialty consultation represents a potentially powerful opportunity for resident learning, but barriers may limit the educational exchanges between fellows (subspecialty registrars) and residents (house officers). We conducted a focus group study of internal medicine (IM) residents and subspecialty fellows to determine barriers against and factors facilitating resident–fellow teaching interactions on the wards, and to identify opportunities for maximising teaching and learning. Methods We conducted four focus groups of IM residents (n = 18) and IM subspecialty fellows (n = 16) at two academic medical centres in the USA during February and March 2013. Participants represented trainees in all 3 years of residency training and seven IM subspecialties. Four investigators analysed the transcripts using a structured qualitative framework approach, which was informed by literature on consultation and the theoretical framework of activity theory. Results We identified two domains of barriers and facilitating factors: personal and systems-based. Sub-themes in the personal domain included fellows' perceived resistance to consultations, residents' willingness to engage in teaching interactions, and perceptions and expectations. Sub-themes in the systems-based domain included the process of requesting the consult, the quality of the consult request, primary team structure, familiarity between residents and fellows, workload, work experience, culture of subspecialty divisions, and fellows' teaching skills. These barriers differentially affected the two stages of the consult identified in the focus groups (initial interaction and follow-up interaction). Conclusions Residents and fellows want to engage in positive teaching interactions in the context of the clinical consult; however, multiple barriers influence both parties in the hospital environment. Many of these barriers are amenable to change. Interventions aimed at reducing barriers to teaching in the setting of consultation hold promise for improving teaching and learning on the wards.

En nuestra primera Ley Federal del Trabajo, en vigor a partir del 28 de agosto de 1931, no existió un procedimiento de huelga, sino normas sustantivas que regulaban el ejercicio del derecho de huelga por parte de los trabajadores; en la segunda versión de nuestra Ley Federal del Trabajo, vigente del 1o. de mayo de 1970 al 30 de abril de 1980, el legislador federal mexicano mantuvo el esquema, sin embargo incorporó normas especiales en la materia, las cuales se conservaron en la reforma procesal del 1o. de mayo de 1980, pero se creó un procedimiento de huelga, el cual no sufrió modificación alguna con motivo de la reforma publicada en el Diario Oficial de la Federación del 30 de noviembre del 2012; por lo tanto, las normas generales previstas en el derecho procesal del trabajo respecto del funcionamiento del Pleno y de las Juntas Especiales, la falta de personalidad, la incompetencia, los impedimentos y excusas, los términos procesales y las notificaciones, así como los incidentes, presentan particularidades en el procedimiento de huelga que las distinguen frente a los demás procedimientos laborales, cuyas características y aplicación constituyen el estudio objeto del presente artículo.

A drawback of targeting soluble antigens such as cytokines or toxins with long-lived antibodies is that such antibodies can prolong the half-life of the target antigen by a "buffering" effect. This has motivated the design of antibodies that bind to target with higher affinity at near neutral pH relative to acidic endosomal pH (∼pH 6.0). Such antibodies are expected to release antigen within endosomes following uptake into cells, whereas antibody will be recycled and exocytosed in FcRn-expressing cells. To understand how the pH dependence of antibody-antigen interactions affects intracellular trafficking, we generated three antibodies that bind IL-6 with different pH dependencies in the range pH 6.0-7.4. The behavior of antigen in the presence of these antibodies has been characterized using a combination of fixed and live cell fluorescence microscopy. As the affinity of the antibody:IL-6 interaction at pH 6.0 decreases, an increasing amount of antigen dissociates from FcRn-bound antibody in early and late endosomes, and then enters lysosomes. Segregation of antibody and FcRn from endosomes in tubulovesicular transport carriers (TCs) into the recycling pathway can also be observed in live cells, and the extent of IL-6 association with TCs correlates with increasing affinity of the antibody:IL-6 interaction at acidic pH. These analyses result in an understanding, in spatiotemporal terms, of the effect of pH dependence of antibody-antigen interactions on subcellular trafficking and inform the design of antibodies with optimized binding properties for antigen elimination.

Folding catalysts of the endoplasmic reticulum (ER), such as protein disulfide isomerase (PDI), accelerate the slow chemical steps, such as disulfide bond formation, that accompany protein folding. Molecular chaperones of the ER, notably the heavy chain-binding protein, BiP (grp78), bind and release unfolded proteins in an ATP-dependent fashion. In vitro, the fate of reduced, denatured lysozyme is dependent on whether the substrate interacts first with BiP or PDI. Depending on the ratio of PDI to substrate and order in which the components of the reaction are mixed, PDI can exhibit a foldase/chaperone activity, which increases the rate and extent of lysozyme refolding, or it can function as an anti-chaperone that promotes the formation of inactive, disulfide-linked lysozyme aggregates (Puig, A., and Gilbert, H.F. (1994) J. Biol. Chem. 269, 7764-7771). Reduced, denatured lysozyme, but not the native protein, interacts with BiP and efficiently stimulates its peptide-dependent ATPase activity. When present at substoichiometric amounts, BiP, like PDI, facilitates the formation of large, inactive lysozyme aggregates that are non-covalently associated with BiP. BiP and PDI compete for a limited number of sites in these insoluble aggregates. If BiP is present at a high molar excess, the chaperone binds unfolded lysozyme and inhibits its aggregation by maintaining it in a soluble, yet inactive, conformation, both in the presence or absence of ATP. Increasing concentrations of BiP decrease the extent, but not the initial rate, of refolding, suggesting that BiP and PDI compete for unfolded lysozyme and that the BiP-lysozyme complex is not a very good substrate for PDI either in the presence or absence of ATP. Depending on the BiP and PDI concentrations, unfolded lysozyme may either be efficiently refolded into the native conformation in a PDI-catalyzed reaction, or it may form both soluble and insoluble BiP-lysozyme complexes. In vitro, PDI- and BiP-facilitated aggregation, as well as the competition of the two proteins for substrate, reproduces many of the features of the quality control system of the ER.

The complexity of protein folding is often aggravated by the low solubility of the denatured state. The inefficiency of the oxidative refolding of reduced, denatured lysozyme results from a kinetic partitioning of the unfolded protein between pathways leading to aggregation and pathways leading to the native structure. Protein disulfide isomerase (PDI), a resident foldase of the endoplasmic reticulum, catalyzes the in vitro oxidative refolding of reduced, disulfide-containing proteins, including denatured lysozyme. Depending on the concentrations of foldase and denatured substrate and the order in which they are added to initiate folding, PDI can exhibit either a chaperone activity or an anti-chaperone activity (Puig, A., and Gilbert, H. F. (1994) J. Biol. Chem 269, 7764-7771). PDI's chaperone activity leads to quantitative recovery of native lysozyme. Its anti-chaperone activity diverts substrate away from productive folding and facilitates disulfide cross-linking of lysozyme into large, inactive aggregates that specifically incorporate PDI. A mutant PDI (NmCm-PDI), in which both the N- and C-terminal active site cysteines have been changed to serines, loses all chaperone activity and behaves as an anti-chaperone at all substrate and PDI concentrations tested. The dithiol/disulfide sites of PDI are essential for the chaperone activity observed at high PDI concentrations, but they are not required for the anti-chaperone activity found at low PDI concentrations. Inactivation of PDI's peptide/protein binding site by a specific photoaffinity label (Noiva, R., Freedman, R. B., and Lennarz, W. J. (1993) J. Biol. Chem. 268, 19210-19217) inhibits the disulfide isomerase and chaperone activity, but the protein still retains its anti-chaperone activity. In a glutathione redox buffer, lysozyme-PDI aggregates are disulfide cross-linked; however, disulfide cross-linking is not required for aggregate formation or for the incorporation of PDI into the aggregates. Although both the peptide binding site and the catalytic active sites of PDI are required for chaperone and disulfide isomerase activity, neither of these sites are involved in PDI's anti-chaperone activity. PDI's anti-chaperone activity could serve as a quality control device by providing an efficient mechanism to retain misfolded proteins in the endoplasmic reticulum (Marquardt, T., and Helenius, A. (1992) J. Cell. Biol. 117, 505-513).

Reduced, denatured lysozyme tends to aggregate at neutral pH, and competition between productive folding and aggregation substantially reduces the efficiency of refolding (Goldberg, M.E., Rudolph, R., and Jaenicke, R. (1991) Biochemistry 30, 2790-2797). Protein disulfide isomerase (PDI), a catalyst of oxidative protein folding, has a variety of effects on the yield of native lysozyme during the oxidative refolding of the reduced, denatured protein. Depending on the concentration of lysozyme, the concentration of PDI, and the order in which lysozyme and PDI are added to initiate folding, PDI can produce a substantial increase or a substantial decrease in the recovery of native lysozyme, when compared with the uncatalyzed reaction. In the presence of a glutathione redox buffer, denatured lysozyme (1-10 microM) partitions almost equally between productive folding leading to native lysozyme (50-63%) and non-productive fates including the formation of disulfide cross-linked aggregates. At the higher lysozyme concentrations examined (5-10 microM), substoichiometric concentrations of PDI (0.5-1 microM) exhibit "anti-chaperone" activity; PDI actively diverts most of the denatured lysozyme away from productive folding so that only 17 +/- 9% of the lysozyme is recovered as native enzyme. PDI's anti-chaperone activity results in extensive intermolecular disulfide crosslinking of lysozyme into large, inactive aggregates. On the other hand, if PDI is initially present at a large molar excess (5-10-fold) when denatured lysozyme is diluted to initiate folding, PDI demonstrates a chaperone-like activity that prevents aggregate formation and promotes correct folding. When PDI's chaperone activity is dominant, virtually all of the denatured lysozyme is correctly folded. The schizophrenic chaperone/anti-chaperone nature of PDI activity accounts for a number of observations on in vivo protein folding, including the necessity for maintaining a high concentration of PDI in the endoplasmic reticulum and the formation of disulfide cross-linked aggregates in the endoplasmic reticulum during the expression of disulfide-containing proteins (deSilva, A., Braakman, I., and Helenius, A. (1993) J. Cell. Biol. 120, 647-655).

How environmental cues regulate adult stem cell and cancer cell activity through surface receptors is poorly understood. Angiopoietin-like proteins (ANGPTLs), a family of seven secreted glycoproteins, are known to support the activity of haematopoietic stem cells (HSCs) in vitro and in vivo. ANGPTLs also have important roles in lipid metabolism, angiogenesis and inflammation, but were considered 'orphan ligands' because no receptors were identified. Here we show that the immune-inhibitory receptor human leukocyte immunoglobulin-like receptor B2 (LILRB2) and its mouse orthologue paired immunoglobulin-like receptor (PIRB) are receptors for several ANGPTLs. LILRB2 and PIRB are expressed on human and mouse HSCs, respectively, and the binding of ANGPTLs to these receptors supported ex vivo expansion of HSCs. In mouse transplantation acute myeloid leukaemia models, a deficiency in intracellular signalling of PIRB resulted in increased differentiation of leukaemia cells, revealing that PIRB supports leukaemia development. Our study indicates an unexpected functional significance of classical immune-inhibitory receptors in maintenance of stemness of normal adult stem cells and in support of cancer development.

Have you ever been curious about how serious fainting, swooning, and syncope are or can be? Have you wondered whether, when, and how to work up these conditions? Have you ever considered how to best treat a patient with single or multiple episodes of syncope? If you have, then the following case vignette should provide a useful stimulus for discussion.

Background: Peer observation of teaching (PoT) is most commonly done as a way of evaluating educators in lecture or small group teaching. Teaching in the clinical environment is a complex and hectic endeavor that requires nimble and innovative teaching on a daily basis. Most junior faculty start their careers with little formal training in education and with limited opportunity to be observed or to observe more experienced faculty. Aim: Formal PoT would potentially ameliorate these challenges. Methods: This article describes a collaborative peer observation process that a group of 11 clinician educators is using as a longitudinal faculty development program. Results: The process described in this article provides detailed and specific teaching feedback for the observed teaching attending while prompting the observing faculty to reflect on their own teaching style and to borrow effective teaching techniques from the observation. Conclusion: This article provides detailed examples from written feedback obtained during collaborative peer observation to emphasize the richness of this combined experience.

We present a case of a previously healthy 30-year-old man who presented with a necrotising pneumonia and bronchiectasis. His infectious workup revealed a Staphylococcus aureus pneumonia. Since bronchiectasis and necrotising pneumonia are unusual findings in an otherwise healthy person, further investigation was pursued. His workup revealed non-classic cystic fibrosis (CF) and allergic bronchopulmonary aspergillosis (ABPA). This case discusses the differential diagnosis of bronchiectasis, the diagnosis and treatment of ABPA, and the role of CF mutations in the pathogenesis of ABPA.