Carprofen Attenuates Postoperative Mechanical and Thermal Hypersensitivity after Plantar Incision in Immunodeficient NSG Mice.

Immunodeficient NSG mice are reported to be less responsive to buprenorphine analgesia. Here, we used NSG mice to compare the efficacy of the commonly used dose of carprofen (5 mg/kg) with 5 and 10 times that dose (25 and 50 mg/kg) for attenuating postoperative mechanical and thermal hypersensitivity following an incisional pain model. Male and female NSG mice (n = 45) were randomly assigned to one of 4 groups and received daily subcutaneous injections for 3 d: saline (5 mL/kg), 5 mg/kg carprofen (Carp5), 25 mg/kg carprofen (Carp25), and 50 mg/kg carprofen (Carp50). Mechanical and thermal hypersensitivity were assessed 24 h before and at 4, 24, and 48 h after surgery. Plasma carprofen concentrations were measured in a separate group of mice (n = 56) on days 0 (at 2, 4, 12, and 23 h), 1, and 2 after the first, second, and third doses, respectively. Toxicity was assessed through daily fecal occult blood testing (n = 27) as well as gross and histopathologic evaluation (n = 15). Our results indicated that the saline group showed both mechanical and thermal hypersensitivity throughout the study. Carp5 did not attenuate mechanical or thermal hypersensitivity at any time point. Carp25 attenuated mechanical and thermal (except for the 4-h time point) hypersensitivity. Carp50 attenuated only thermal hypersensitivity at 24 h. Fecal occult blood was detected in 1 of 8 Carp25-treated mice at 48 and 72 h. Histopathologic abnormalities (gastric ulceration, ulcerative enteritis, and renal lesions) were observed in some Carp50-treated mice. Plasma carprofen concentrations were dose and time dependent. Our results indicate that Carp25 attenuated postoperative mechanical and thermal hypersensitivity more effectively than Carp5 or Carp50 in NSG mice with incisional pain. Therefore, we recommend providing carprofen at 25 mg/kg SID for incisional pain procedures using immunodeficient NSG mouse.

High Shear Stress Reduces ERG Causing Endothelial-Mesenchymal Transition and Pulmonary Arterial Hypertension.

Pathological high shear stress (HSS, 100 dyn/cm 2 ) is generated in distal pulmonary arteries (PA) (100-500 µm) in congenital heart defects and in progressive PA hypertension (PAH) with inward remodeling and luminal narrowing. Human PA endothelial cells (PAEC) were subjected to HSS versus physiologic laminar shear stress (LSS, 15 dyn/cm 2 ). Endothelial-mesenchymal transition (EndMT), a feature of PAH not previously attributed to HSS, was observed. H3K27ac peaks containing motifs for an ETS-family transcription factor (ERG) were reduced, as was ERG-Krüppel-like factors (KLF)2/4 interaction and ERG expression. Reducing ERG by siRNA in PAEC during LSS caused EndMT; transfection of ERG in PAEC under HSS prevented EndMT. An aorto-caval shunt was preformed in mice to induce HSS and progressive PAH. Elevated PA pressure, EndMT and vascular remodeling were reduced by an adeno-associated vector that selectively replenished ERG in PAEC. Agents maintaining ERG in PAEC should overcome the adverse effect of HSS on progressive PAH.

Fiordo / Fjord

Estas historias de la LIBRETA DE VIAJE DEL MÉDICO DE FAMILIA, que forman una biblioteca del médico caminante o viajero emocional, son hojas sueltas en las que se escribe sobre paisajes y emociones; son un atlas de geografía emocional. La evocación de un paisaje ante la asistencia a un paciente —montañas, ríos, valles, playas, mares, desiertos, mesetas, islas, pantanos, cascadas, dunas, bosques, salinas, lagos, etc.—, con las sensaciones sentidas por el médico, de calor, frescor, humedad, dificultad, agobio, serenidad, inmensidad, soledad, etc. No es un diario, solo una libreta de apuntes con las vivencias del médico sobre los patrones y procesos de la consulta en un cierto caso clínico, que, a su vez, puede ilustrar un prototipo de esa clase de casos.(AU)

These stories of THE FAMILY PHYSICIAN’S TRAVEL NOTEBOOK, which comprise a library of the nomadic doctor or emotional traveller, are loose-leaf pages with writings about landscapes and emotions. They are an emotional geography atlas. The suggestion of a landscape before treating a patient –mountains, rivers, valleys, beaches, seas, deserts, plateaus, islands, swamps, waterfalls, dunes, forests, salt marshes, lakes, etc.-, with the sensations felt by the doctor -heat, coolness, humidity, hardship, stress, serenity, vastness, loneliness, etc. It is not a journal, only a notebook with the physician’s experiences about the patterns and processes of consultation in a particular case study, which in turn may illustrate a prototype for these types of cases.(AU)

Adjuvanting a subunit SARS-CoV-2 vaccine with clinically relevant adjuvants induces durable protection in mice.

Adjuvants enhance the magnitude and the durability of the immune response to vaccines. However, there is a paucity of comparative studies on the nature of the immune responses stimulated by leading adjuvant candidates. In this study, we compared five clinically relevant adjuvants in mice-alum, AS03 (a squalene-based adjuvant supplemented with α-tocopherol), AS37 (a TLR7 ligand emulsified in alum), CpG1018 (a TLR9 ligand emulsified in alum), O/W 1849101 (a squalene-based adjuvant)-for their capacity to stimulate immune responses when combined with a subunit vaccine under clinical development. We found that all four of the adjuvant candidates surpassed alum with respect to their capacity to induce enhanced and durable antigen-specific antibody responses. The TLR-agonist-based adjuvants CpG1018 (TLR9) and AS37 (TLR7) induced Th1-skewed CD4+ T cell responses, while alum, O/W, and AS03 induced a balanced Th1/Th2 response. Consistent with this, adjuvants induced distinct patterns of early innate responses. Finally, vaccines adjuvanted with AS03, AS37, and CpG1018/alum-induced durable neutralizing-antibody responses and significant protection against the B.1.351 variant 7 months following immunization. These results, together with our recent results from an identical study in non-human primates (NHPs), provide a comparative benchmarking of five clinically relevant vaccine adjuvants for their capacity to stimulate immunity to a subunit vaccine, demonstrating the capacity of adjuvanted SARS-CoV-2 subunit vaccines to provide durable protection against the B.1.351 variant. Furthermore, these results reveal differences between the widely-used C57BL/6 mouse strain and NHP animal models, highlighting the importance of species selection for future vaccine and adjuvant studies.

Extended-release Buprenorphine, an FDAindexed Analgesic, Attenuates Mechanical Hypersensitivity in Rats (Rattus norvegicus).

A new extended-release buprenorphine (XR), an FDA-indexed analgesic, has recently become available to the laboratory animal community. However, the effectiveness and dosing of XR has not been extensively evaluated for rats. We investigated XR's effectiveness in attenuating postoperative hypersensitivity in a rat incisional pain model. We hypothesized that high dose of XR would attenuate mechanical and thermal hypersensitivity more effectively than the low dose of XR in this model. We performed 2 experiments. In experiment 1, male adult Sprague-Dawley rats (n = 31) were randomly assigned to 1 of the 4 treatment groups: 1) saline (saline, 0.9% NaCl, 5 mL/kg, SC, once); 2) sustained-release buprenorphine (Bup-SR; 1.2 mg/kg, SC, once), 3) low-dose extended-release buprenorphine (XR-Lo; 0.65 mg/kg, SC, once), and 4) high-dose extended-release buprenorphine (XR-Hi; 1.3 mg/kg, SC, once). After drug administration, a 1 cm skin incision was made on the plantar hind paw under anesthesia. Mechanical and thermal hypersensitivity were evaluated 1 d before surgery (D-1), 4 h after surgery (D0), and for 3 d after surgery (D1, D2, and D3). In experiment 2, plasma buprenorphine concentration (n = 39) was measured at D0, D1, D2, and D3. Clinical observations were recorded daily, and a gross necropsy was performed on D3. Mechanical and thermal hypersensitivity were measured for 3 d (D0-D3) in the saline group. Bup-SR, XR-Lo, and XR-Hi effectively attenuated mechanical hypersensitivity for D0-D3. Plasma buprenorphine concentrations remained above 1 ng/mL on D0 and D1 in all treatment groups. No abnormal clinical signs were noted, but injection site reactions were evident in the Bup-SR (71%), XR-Lo (75%), and XR-Hi (87%) groups. This study indicates that XR-Hi did not attenuate hypersensitivity more effectively than did XR-Lo in this model. XR 0.65 mg/kg is recommended to attenuate postoperative mechanical hypersensitivity for up to 72 h in rats in an incisional pain model.

Estrecho marítimo / Strait

Estas historias de la LIBRETA DE VIAJE DEL MÉDICO DE FAMILIA, que forman una biblioteca del médico caminante o viajero emocional, son hojas sueltas en las que se escribe sobre paisajes y emociones; son un atlas de geografía emocional. La evocación de un paisaje ante la asistencia a un paciente -montañas, ríos, valles, playas, mares, desiertos, mesetas, islas, pantanos, cascadas, dunas, bosques, salinas, lagos, etc.-, con las sensaciones sentidas por el médico, de calor, frescor, humedad, dificultad, agobio, serenidad, inmensidad, soledad, etc. No es un diario, sólo una libreta de apuntes con las vivencias del médico sobre los patrones y procesos de la consulta en un cierto caso clínico, que a su vez, puede ilustrar un prototipo de esa clase de casos (AU)

These stories of the THE FAMILY PHYSICIAN’S TRAVEL NOTEBOOK, which form a library of the walking doctor or emotional traveler, are loose-leaf pages with writings about landscapes and emotions; they are an atlas of emotional geography. The evocation of a landscape before attending a patient -mountains, rivers, valleys, beaches, seas, deserts, plateaus, islands, swamps, waterfalls, dunes, forests, salt marshes, lakes, etc.-, with the sensations felt by the doctor -heat, coolness, humidity, hardship, stress, serenity, vastness, loneliness, etc. It is not a diary, only a notebook with the doctor's experiences about the patterns and processes of consultation in a clinical case, which in turn may illustrate a prototype for this type of cases (AU)

Montaña / Mountain

Estas historias de la LIBRETA DE VIAJE DEL MÉDICO DE FAMILIA, que forman una biblioteca del médico caminante o viajero emocional, son hojas sueltas en las que se escribe sobre paisajes y emociones; son un atlas de geografía emocional. La evocación de un paisaje ante la asistencia a un paciente -montañas, ríos, valles, playas, mares, desiertos, mesetas, islas, pantanos, cascadas, dunas, bosques, salinas, lagos, etc.-, con las sensaciones sentidas por el médico, de calor, frescor, humedad, dificultad, agobio, serenidad, inmensidad, soledad, etc. No es un diario, sólo una libreta de apuntes con las vivencias del médico sobre los patrones y procesos de la consulta en un cierto caso clínico, que a su vez, puede ilustrar un prototipo de esa clase de casos (AU)

These stories of the THE FAMILY PHYSICIAN’S TRAVEL NOTEBOOK, which form a library of the walking doctor or emotional traveler, are loose-leaf pages with writings about landscapes and emotions; they are an atlas of emotional geography. The evocation of a landscape before attending a patient -mountains, rivers, valleys, beaches, seas, deserts, plateaus, islands, swamps, waterfalls, dunes, forests, salt marshes, lakes, etc.-, with the sensations felt by the doctor -heat, coolness, humidity, hardship, stress, serenity, vastness, loneliness, etc. It is not a diary, only a notebook with the doctor's experiences about the patterns and processes of consultation in a clinical case, which in turn may illustrate a prototype for this type of cases (AU)

Aprendiendo conceptos del diagnóstico en medicina de familia: a propósito del "signo de Robinson" - las huellas que no deberían estar allí / Learning concepts of diagnosis in family medicine: the “mark robinson sign” - the traces that should not be there

A propósito de cinco casos en donde el proceso diagnóstico se inició en 'la huella que no debería estar allí' o 'signo de Robinson' -como le pasó a Robinson Crusoe que vio una huella humana en la playa de su isla 'desierta': ¿cómo podía encontrarse allí?; era un misterio-, y basándonos en metáforas, revisamos los mecanismos de la operación mental de identificar la enfermedad en medicina de familia. Encuadramos el mecanismo de 'la huella que no debería estar allí' principalmente en la primera fase o intuitiva del razonamiento clínico, pero esta intuición del médico debe mantenerse acompañando a todo el proceso diagnóstico, como el 'bajo continuo' de la música barroca, permitiendo la improvisación y el estilo personal, y de este modo, eventualmente la observación de la huella 'que no tenía que estar allí' puede surgir tanto en la fase analítica como en la de verificación de las hipótesis elaboradas

We review the mechanisms of the mental operation to identify the disease in family medicine, using five cases where the diagnosis process began in 'the trace that should not be there' or 'Robinson sign' as happened to Robinson Crusoe when he saw a human footprint on the beach of the 'desert island'. How could it be there?; It was a mystery, and based on metaphors, we framed the mechanism of 'the trace that should not be there' mainly in the first phase of clinical or intuitive reasoning, but this intuition of the doctor should be accompanied by the diagnostic process, like the 'basso continuo' of Baroque music, allowing improvisation and personal style, and in this way, eventually observing the footprint 'that should not have been there' that may arise in the analytical, as well as in the verification phase of the assumptions made

Observaciones, intuiciones y anécdotas, desde la perspectiva del médico, para una teoría de la historia natural de la continuidad interpersonal. Los colores del tiempo / Observations, insights and anecdotes from the perspective of the physician, for a theory of the natural history of interpersonal continuity. The colors of time

Se aportan elementos para una teoría de la historia natural de la continuidad interpersonal, desde la perspectiva del médico de familia, analizada en base a la reflexión y el recuerdo de dos médicos respecto a su relación con sus pacientes durante 30 años en que han trabajado en el mismo lugar. Es un viaje por los “colores de la historia natural de la continuidad interpersonal”, que cambian al paso del tiempo. Se observa un escenario de demanda creciente cada vez más trivial, con una falta de comprensión por parte del paciente de lo que constituye una buena calidad científico técnica y una comunicación con el médico inapropiada, con una defensa cognitiva y conductual del médico. Podrían describirse distintas tipologías de continuidad interpersonal, que se combinan a lo largo del tiempo, y que esta podría ser discontinua, y experimentarse como “momentos”, presentando efectos positivos y negativos (AU)

Elements for a theory of natural history of interpersonal continuity are provided, from the perspective of the family doctor, analyzed on the reflection and remembrance of two doctors regarding their relationship with their patients during 30 years working in the same place. It is a journey through the “colors of the natural history of interpersonal continuity”, which change over time. A scenario of increasingly trivial growing demand is observed, with a lack of understanding by the patient of what constitutes a good scientific and technical quality and an inappropriate communication with the doctor, which causes a cognitive and behavioral defense from the family doctor. They may describe different types of interpersonal continuity, which combine over time, and that it could be discontinuous, and experienced as “moments”, presenting positive and negative effects (AU)

Libreta de viaje del médico de familia. Iceberg / Family physician´s travel notebook. Iceberg

Estas historias de la LIBRETA DE VIAJE DEL MÉDICO DE FAMILIA, que forman una biblioteca del médico caminante o viajero emocional, son hojas sueltas en las que se escribe sobre paisajes y emociones; son un atlas de geografía emocional. La evocación de un paisaje ante la asistencia a un paciente –montañas, ríos, valles, playas, mares, desiertos, mesetas, islas, pantanos, cascadas, dunas, bosques, salinas, lagos, etc.-, con las sensaciones sentidas por el médico, de calor, frescor, humedad, dificultad, agobio, serenidad, inmensidad, soledad, etc. No es un diario, solo una libreta de apuntes con las vivencias del médico sobre los patrones y procesos de la consulta en un cierto caso clínico, que a su vez, puede ilustrar un prototipo de esa clase de casos (AU)

These stories of the FAMILY PHYSICIAN’S TRAVEL NOTEBOOK, which form a library of the walking doctor or emotional traveler, are loose sheets with writings about landscapes and emotions; they are an atlas of emotional geography. The evocation of a landscape before attending a patient –mountains, rivers, valleys, beaches, seas, deserts, plateaus, islands, swamps, waterfalls, dunes, forests, salt marshes, lakes, etc.-, with the sensations felt by the doctor -heat, coolness, humidity, hardship, stress, serenity, vastness, loneliness, etc. It is not a diary, only a notebook with the doctor’s experiences about the patterns and processes of consultation in a clinical case, which in turn may illustrate a prototype for this type of cases (AU)

[Learning concepts of diagnosis in family medicine: the "mark robinson sign" - the traces that should not be there]. / Aprendiendo conceptos del diagnóstico en medicina de familia: a propósito del «signo de Robinson¼ - las huellas que no deberían estar allí.

We review the mechanisms of the mental operation to identify the disease in family medicine, using five cases where the diagnosis process began in "the trace that should not be there" or "Robinson sign" as happened to Robinson Crusoe when he saw a human footprint on the beach of the "desert island". How could it be there?; It was a mystery, and based on metaphors, we framed the mechanism of "the trace that should not be there" mainly in the first phase of clinical or intuitive reasoning, but this intuition of the doctor should be accompanied by the diagnostic process, like the "basso continuo" of Baroque music, allowing improvisation and personal style, and in this way, eventually observing the footprint "that should not have been there" that may arise in the analytical, as well as in the verification phase of the assumptions made.

El maestro sabio o las treinta mil leyes de las cuatro estaciones (última parte) / The wise master or the thirty thousand laws of the four seasons (last chapter)

Esta es la última entrega de una serie de cuatro artículos muy especiales sobre la historia del maestro sabio, Gin y Seng, y su aprendiz de nombre cambiante. El maestro es el descubridor de un cierto número de Leyes Docentes Científicas de la Formación de Aprendices que han revolucionado el mundo educativo. Son las leyes que gobiernan el universo de la formación del aprendiz; son inalterables y válidas por sí mismas. Existen desde un tiempo sin comienzo. En una clara alegoría a la formación de los médicos internos residentes, los autores nos van describiendo las etapas por las que pasan los residentes, desde sus inicios titubeantes (primavera) hasta su actuación independiente (invierno), y nos dan las claves de lo que debe ser la labor de tutorización, desarrollando un completo curso de formación para tutores de residentes (AU)

This is the last chapter of a series of four very special articles on the story of the wise master, Gin and Seng, and his apprentice with changing name. The master is the discoverer of a certain number of Scientific Teaching Laws for Apprentices Training which have revolutionized the world of education. These are the three rules governing the education of apprentices; they are inalterable and valid by themselves. They have existed from a time with no beginning. In a clearly allegorical story of the training period of hospital medical residents, the authors describe the different stages that residents go through, from their hesitating start (spring) to their independent performance (winter), while providing the keys to the correct tutoring tasks, creating a complete training course for medical residents tutors (AU)

El maestro sabio o las treinta mil leyes de las cuatro estaciones (tercera parte) / The wise master, or the thirty thousand laws of the four seasons (part three)

Esta es la tercera entrega de una serie de cuatro artículos muy especiales sobre la historia del maestro sabio, Gin y Seng, y su aprendiz de nombre cambiante. El maestro es el descubridor de un cierto número de Leyes Docentes Científicas de la Formación de Aprendices que han revolucionado el mundo educativo. Son las leyes que gobiernan el universo de la formación del aprendiz; son inalterables y válidas por sí mismas. Existen desde un tiempo sin comienzo. En una clara alegoría a la formación de los médicos internos residentes, los autores nos van describiendo las etapas por las que pasan los residentes, desde sus inicios titubeantes (primavera) hasta su actuación independiente (invierno), y nos dan las claves de lo que debe ser la labor de tutorización, desarrollando un completo curso de formación para tutores de residentes (AU)

This is the third part of a series of four very special articles about the story of the wise master, Gin y Seng and his assistant, of changing name. The master is the discoverer of a certain number of Scientific Teaching Laws on Apprentice Training which have revolutionized the world of education. They are the laws which govern the apprentice’s learning universe; they are inalterable and valid in their own right. They have existed for a time without beginning. In a clear allegory of the training of Resident Medical Interns, the writers gradually describe the stages through which the residents go, from their hesitant beginnings (spring) to acting independently (winter) and we are given the keys to what must be the labour of tutoring, developing a complete training course for resident tutors (AU)

Reflexiones sobre el presente y el futuro de la medicina de familia / Reflections on the present and future of family medicine

No disponible

El maestro sabio o las treinta mil leyes de las cuatro estaciones (segunda parte) / The wise master or the thirty thousand laws of the four seasons (part 2

Con esta segunda entrega continúa la publicación de una serie de cuatro artículos muy especiales, sobre la historia del maestro sabio, Gin y Seng, y su aprendiz de nombre cambiante. En una clara alegoría a la formación de los médicos internos residentes, los autores nos van describiendo las etapas por las que pasan los residentes, desde sus inicios titubeantes (primavera) hasta su actuación independiente (invierno), y nos dan las claves de lo que debe ser la labor de tutorización, desarrollando un completo curso de formación para tutores de residentes. Revista Clínica de Medicina de Familia quiere así hacer un pequeño hueco en sus páginas para una de las labores fundamentales de muchos de nuestros lectores, que tienen en sus manos la responsabilidad de formar a los futuros especialistas (AU)

Following the publication of a series of four very special articles on the story of the wise master, Gin and Seng, and his apprentice with changing name, here is the second part of the series. In a clearly allegorical story of the training period of hospital medical residents, the authors describe the different stages that residents go through, from their hesitating start (spring) to their independent performance (winter), while providing the keys to the correct tutoring tasks, creating a complete training course for medical residents tutors. Revista Clínica de Medicina de Familia thus intends to create a small space in its pages for one of the essential tasks of many of our readers who bear the responsibility of training future specialists (AU)

El maestro sabio o las treinta mil leyes de las cuatro estaciones (primera parte) / The wise master or the thirty thousand laws of the four seasons (first part)

Con esta primera entrega iniciamos la publicación de una serie de cuatro artículos muy especiales, sobre la historia del maestro sabio, Gin y Seng, y su aprendiz de nombre cambiante. En una clara alegoría a la formación de los médicos internos residentes, los autores nos van describiendo las etapas por las que pasan los residentes, desde sus inicios titubeantes (primavera) hasta su actuación independiente (invierno), y nos dan las claves de lo que debe ser la labor de tutorización, desarrollando un completo curso de formación para tutores de residentes. Revista Clínica de Medicina de Familia quiere así hacer un pequeño hueco en sus páginas para una de las labores fundamentales de muchos de nuestros lectores, que tienen en sus manos la responsabilidad de formar a los futuros especialistas (AU)

The wise master or the thirty thousand laws of the four seasons (first part). In this first issue, we begin the publication of a series of four very special articles about the story of the wise master Gin y Seng, and his apprentice with a changing name. In a clear allegory of the training of resident medical interns, the authors set about describing the stages which the residents go through, from their hesitant beginnings (spring) to their independent actions (winter), and they give us key insight into what the labour of tutoring should be, developing a complete training course for tutors of residents. Revista Clínica de Medicina de Familia (Medical Journal of Family Medicine) thus wishes to create a small space in its pages for one of the fundamental jobs of many of our readers, in whose hands lies the responsibility to train future specialists (AU)

Senderos clínicos en la presentación de los síntomas, considerados como obra de arte plástica, en medicina de familia / Clinical pathways in the presentation of symptoms, considered as a plastic work of art in Family Medicine

No disponible

Los síntomas en medicina de familia no son síntomas de enfermedad, sino síntomas de vida / The symptoms in family medicine are not symptoms of disease, they are symptoms of life

Los síntomas en medicina de familia no son señales de enfermedad, sino «de vida»; en la consulta «entra, junto al paciente, toda su vida». Cada consulta es primariamente un problema biopsicosocial: el individuo en relación con su Yo y su contexto percibe una disfunción o alteración. Fundamentar la valoración en la sola molestia física expuesta por el paciente puede ser un error al no haber identificado el problema real. Las distintas tipologías posibles de los síntomas están «enmarañadas» o encadenadas unas con otras: los síntomas pueden ser apropiados o inevitables; ser expresiones de alteraciones bioquímicas, símbolos para el paciente, expresiones del contexto grupal, o modos de afrontar una situación; y dependen del funcionamiento psicológico previo del paciente, la severidad del déficit de la función psicológica asociada a la enfermedad, las habilidades residuales, la adaptación y el afrontamiento de las limitaciones funcionales, la relación médico-paciente, así como de la influencia del contexto(AU)

The symptoms in family medicine are not signs of disease, but "signs of life"; in the consultation "all patient life comes together with him". Every consultation is primarily a biopsicosocial problem: the person perceives a dysfunction or alteration in relation with himself and his context. To do a diagnosis only with physical symptoms, can be a mistake because these do not identify the real problem. The different types of symptoms are "entangled" or chained some in others: the symptoms can be fitted or inevitable; to be expressions of biochemical alterations, symbols for the patient, group context expressions, or kinds of facing the facts; and they depend on the previous psychological patient performance, the severity of the deficit of the psychological function associated with the disease, the residual skills, the adjustment and the confrontation of the functional limitations, the relation doctor-patient, as well as on the influence of the context(AU)