Scn1a haploinsufficiency in the prefrontal cortex engages to cognitive impairment and depressive phenotype.

Altered development and function of the prefrontal cortex (PFC) during adolescence is implicated in the origin of mental disorders. Deficits in the GABAergic system prominently contribute to these alterations. Nav1.1 is a voltage-gated Na+ channel critical for normal GABAergic activity. Here, we studied the role of Nav1.1 in PFC function and its potential relationship with the aetiology of mental disorders. Dysfunction of Nav1.1 activity in the medial PFC (mPFC) of adolescent mice enhanced the local excitation/inhibition ratio, resulting in epileptic activity, cognitive deficits and depressive-like behaviour in adulthood, along with a gene expression profile linked to major depressive disorder (MDD). Additionally, it reduced extracellular serotonin concentration in the dorsal raphe nucleus and brain-derived neurotrophic factor expression in the hippocampus, two MDD-related brain areas beyond the PFC. We also observed alterations in oscillatory activity and impaired hippocampal-mPFC coherence during sleep. Finally, we found reduced expression levels of SCN1A, the gene encoding Nav1.1, in post-mortem PFC samples from human MDD subjects. Collectively, our results provide a novel mechanistic framework linking adolescence-specific alterations in Nav1.1 function in the PFC to the pathogenesis of epilepsy and comorbidities such as cognitive impairment and depressive disorders.

Family and Community Medicine and its role in preventing health overuse (preventive, diagnostic, therapeutic and rehabilitative). / Medicina de Familia y Comunidad y su papel en evitar los excesos sanitarios (preventivos, diagnósticos, terapéuticos y rehabilitadores).

In Medicine, it is critical "to offer 100% of what is needed and avoid 100% of what is not needed." Unfortunately, this primary issue is challenging, and generally, more than required is offered, and everything that is unnecessary is not avoided. This is a nonsystematic review with a teaching objective that reviews the general issue in primary care and suggests ways to avoid overuse and shortcomings concerning preventive, diagnostic, therapeutic, and rehabilitative interventions. Knowing not to do is science and art that is hardly taught and practiced less. The overuse that harm are an almost daily part of clinical practice in prevention, diagnosis, treatment, and rehabilitation. It is essential to promote "the art and science of not doing".

En Medicina es clave "ofrecer el 100% de lo que se precisa y evitar el 100% de lo que no se precisa". Lamentablemente, es difícil cumplir con esta cuestión clave y generalmente se ofrece más de lo que se precisa y no se evita todo lo que no se precisa. Este texto es una revisión no sistemática con objetivo docente en que se revisa el problema general en atención primaria y se proponen formas de evitar los excesos y defectos respecto a intervenciones preventivas, diagnósticas, terapéuticas y de rehabilitación. Saber no hacer es ciencia y arte que se enseña poco y se practica menos. Los excesos que dañan son parte casi diaria de la práctica clínica, en prevención, diagnóstico, tratamiento y rehabilitación. Es imprescindible fomentar "el arte y la ciencia de no hacer".

Medicina de Familia y Comunidad y su papel en evitar los excesos sanitarios (preventivos, diagnósticos, terapéuticos y rehabilitadores) / Family and Community Medicine and its role in preventing health overuse (preventive, diagnostic, therapeutic and rehabilitative)

Resumen En Medicina es clave "ofrecer el 100% de lo que se precisa y evitar el 100% de lo que no se precisa". Lamentablemente, es difícil cumplir con esta cuestión clave y generalmente se ofrece más de lo que se precisa y no se evita todo lo que no se precisa. Este texto es una revisión no sistemática con objetivo docente en que se revisa el problema general en atención primaria y se proponen formas de evitar los excesos y defectos respecto a intervenciones preventivas, diagnósticas, terapéuticas y de rehabilitación. Saber no hacer es ciencia y arte que se enseña poco y se practica menos. Los excesos que dañan son parte casi diaria de la práctica clínica, en prevención, diagnóstico, tratamiento y rehabilitación. Es imprescindible fomentar "el arte y la ciencia de no hacer".

Abstract In Medicine, it is critical "to offer 100% of what is needed and avoid 100% of what is not needed." Unfortunately, this primary issue is challenging, and generally, more than required is offered, and everything that is unnecessary is not avoided. This is a nonsystematic review with a teaching objective that reviews the general issue in primary care and suggests ways to avoid overuse and shortcomings concerning preventive, diagnostic, therapeutic, and rehabilitative interventions. Knowing not to do is science and art that is hardly taught and practiced less. The overuse that harm are an almost daily part of clinical practice in prevention, diagnosis, treatment, and rehabilitation. It is essential to promote "the art and science of not doing".

Long-lasting memory deficits in mice withdrawn from cocaine are concomitant with neuroadaptations in hippocampal basal activity, GABAergic interneurons and adult neurogenesis.

Cocaine addiction disorder is notably aggravated by concomitant cognitive and emotional pathology that impedes recovery. We studied whether a persistent cognitive/emotional dysregulation in mice withdrawn from cocaine holds a neurobiological correlate within the hippocampus, a limbic region with a key role in anxiety and memory but that has been scarcely investigated in cocaine addiction research. Mice were submitted to a chronic cocaine (20 mg/kg/day for 12 days) or vehicle treatment followed by 44 drug-free days. Some mice were then assessed on a battery of emotional (elevated plus-maze, light/dark box, open field, forced swimming) and cognitive (object and place recognition memory, cocaine-induced conditioned place preference, continuous spontaneous alternation) behavioral tests, while other mice remained in their home cage. Relevant hippocampal features [basal c-Fos activity, GABA+, parvalbumin (PV)+ and neuropeptide Y (NPY)+ interneurons and adult neurogenesis (cell proliferation and immature neurons)] were immunohistochemically assessed 73 days after the chronic cocaine or vehicle protocol. The cocaine-withdrawn mice showed no remarkable exploratory or emotional alterations but were consistently impaired in all the cognitive tasks. All the cocaine-withdrawn groups, independent of whether they were submitted to behavioral assessment or not, showed enhanced basal c-Fos expression and an increased number of GABA+ cells in the dentate gyrus. Moreover, the cocaine-withdrawn mice previously submitted to behavioral training displayed a blunted experience-dependent regulation of PV+ and NPY+ neurons in the dentate gyrus, and neurogenesis in the hippocampus. Results highlight the importance of hippocampal neuroplasticity for the ingrained cognitive deficits present during chronic cocaine withdrawal.

Crying patients in General/Family Practice: incidence, reasons for encounter and health problems / Pacientes que choram em Medicina Geral/de Família: incidência, razões de consulta e problemas de saúde / Pacientes que lloran en Medicina General/de Familia: incidencia, razones de consulta y problemas de salud

Context: Despite evidence demonstrating the benefits of understanding patients, there is a paucity of information about how physicians address psychological and social concerns of patients. No one study has been published about the incidence of crying in General/Family Practice. Objective: To know the incidence of crying in primary care/general practice, and the patients' characteristics, their reasons for encounter and their health problems. Design: A descriptive, prospective study, of one year, of three general practitioners/family physicians in Madrid, Spain. Setting: primary care (doctors' office and patients' home). Subjects: Face to face encounters with crying patients. Main outcome measure: At least one rolling tear. Results: Patients cried in 157 encounters out of a total of 18,627 giving an incidence rate of 8.4 per thousand. More frequent reasons for encounters were: feeling depressed (12.7%), social handicap (mainly social isolation/living alone) (6.4%), relationship problem with partner (5.1%) and feeling anxious (3.2%). More frequent health problems were: depressive disorder (23.6%), anxiety disorder (8.3%), cerebrovascular disease (5.1%) and loss/death of partner (3.8%). Conclusions: Crying in primary care is not uncommon. Reasons for crying cover the whole range of human problems, mainly social and psychological problems.

Contexto: Apesar de estudos que demonstram os benefícios de se compreender o paciente, há escassa informação sobre como os médicos respondem aos problemas psicológicos e sociais. Não encontramos nenhum trabalho publicado sobre a incidência de pacientes que choram. Objetivo: Conhecer a incidência do choro em Medicina Geral/de Família e as características dos pacientes, suas razões de consulta e seus problemas de saúde. Desenho: Estudo descritivo, prospectivo, com um ano de duração, por três clínicos gerais/médicos de família em Madri, Espanha. Local: Atenção Primária (consultórios médicos e casas dos pacientes). Pacientes: Encontros face a face com pacientes que choram. Parâmetro principal: Pelo menos uma lágrima derramada. Resultados: Pacientes choraram em 157 encontros de um total de 18.627, uma incidência de 8,4 por mil. Os motivos mais frequentes de consulta foram: sentir-se deprimido (12,7%), limitações sociais (principalmente, o isolamento/estar sozinho) (6,4%), problemas de relacionamento (5,1%) e sensação de ansiedade (3,2%). Os problemas de saúde mais comuns: depressão (23,6%), ansiedade (8,3%), doença cerebrovascular (5,1%) e perda/morte de um parceiro (3,8%). Conclusões: Chorar não é incomum na Atenção Primária. As razões para chorar cobrem um amplo espectro de problemas humanos, principalmente problemas sociais e psicológicos.

Contexto: A pesar de los estudios que demuestran los beneficios de comprender al paciente, hay escasa información sobre cómo los médicos responden a los problemas psicológicos y sociales. No hemos encontrado ningún trabajo publicado sobre la incidencia de pacientes que lloran. Objetivo: Conocer la incidencia del llanto en Medicina General/de Familia y las características de los pacientes, las razones de sus consultas y sus problemas de salud. Diseño: Estudio descriptivo, prospectivo, de un año de duración, realizado por tres especialistas de Medicina General/de Familia, en Madrid, España. Lugar: Atención Primaria (consultas médicas realizadas en consultorios y consultas domiciliarias). Pacientes: Encuentros "cara a cara" con pacientes que lloran. Parámetro principal: Al menos una lágrima derramada. Resultado: Lloraron pacientes en 157 encuentros de un total de 18.627, lo que resulta en una incidencia de 8,4 por mil. Las razones de consulta más frecuentes fueron: sentimiento depresivo (12,7%), limitaciones sociales (fundamentalmente, aislamiento/vivir solo) (6,4%), problemas de pareja (5,1%) y sentimiento de ansiedad (3,2%). Los problemas de salud más frecuentes fueron: depresión (23,6%), ansiedad (8,3%), enfermedad cerebrovascular (5,1%) y pérdida/muerte de la pareja (3,8%). Conclusiones: Llorar no es raro en la atención primaria. Las razones para llorar cubren el amplio campo de los problemas humanos, principalmente problemas sociales y psicológicos.

[Longitudinality, prestige, good reputation (social and professional) and general/family medicine. Clinical and public health aspects. SESPAS Report 2012]. / Longitudinalidad, prestigio, buena reputación (social y profesional) y medicina general/de familia. Aspectos clínicos y de salud pública. Informe SESPAS 2012.

The reform of primary care in Spain in 1984 focussed mainly on skills and knowledge (physician training and working hours) and material resources (new buildings). The reform did not succeed in improving longitudinal care nor did it give primary care physicians greater power, that is, the reform did not increase coordination or strengthen the central role of the family physician in services provision. The lack of longitudinality has persisted over the years since the working methods that encourage it (and its resulting clinical and public health benefits) have not been stimulated. Longitudinality is the personal relationship established over the years between general practitioners and their patients and is defined as (a) care by the same family physician of most of the patient's problems throughout his or her life, and (b) the recognition by patients and the population of a stable source of care to be used for initial contact and for the follow-up of problems. The tendency in the medical profession and society at large is to respond to an increasing number of health problems more quickly and intensely, with increasingly powerful means and with a greater number of specialists. In turn, this tendency makes medical activities dangerous. To counteract this tendency, a motto of "less is better" should be adopted, implying greater longitudinality. Many initiatives could improve longitudinality, such as incentives for not moving, increasing the capitation component of remuneration to nearly 50%, broadening the range of general practitioners' skills, including family members in the same patient list, and transforming the role of specialists into that of consultants.

Barbara Starfield / No disponible

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[Ethical and practical problems of secondary prevention. Two paediatrics examples]. / Problemas prácticos y éticos de la prevención secundaria. A propósito de dos ejemplos en pediatría.

The concept of prevention is surrounded by a halo of optimism that can sometimes confuse, since it is not always borne out by the facts. The saying, "An ounce of prevention is worth a pound of cure", is not always true. Moreover, preventive activities should be based on a much more solid scientific basis than curative activities, since we offer the former as an option, whereas we are required to provide the latter. This article reviews two examples of paediatric screening instruments-one for neuroblastoma, and the other for hip dysplasia-which provide an opportunity to evaluate the practical problems of secondary prevention. These two instruments are used to examine a few general but important issues in screening, such as the need to know the natural history of the disease, and the "point of no return" (the moment past which early diagnosis and early intervention are no longer so effective in improving the course of the disease). In conclusion, only sometimes "an ounce of cure is worth a pound of prevention", and regardless of the value of a given screening instrument, clinicians should use the same level of scientific rigor to judge preventive activities as they use for curative activities.

Poco nuevo relevante sobre la prevención secundaria del cáncer de mama / Little relavant news on secondary prevention of breast cancer

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Problemas prácticos y éticos de la prevención secundaria. A propósito de dos ejemplos en pediatría / Ethical and practical problems of secondary prevention. Two paediatrics examples

pues no se corresponde con los hechos. Decimos que “más vale prevenir que curar” y en muchos casos no es cierto. Además, las actividades preventivas deberían tener mucho mayor fundamento científico que las curativas, pues aquellas las solemos ofrecer y éstas nos son requeridas. En este texto revisamos dos ejemplos pediátricos de cribado, el del neuroblastoma y el de la displasia de cadera, que sirven para valorar los problemas prácticos de la prevención secundaria. Con ellos se examinan algunas cuestiones generales e importantes en el cribado, como la necesidad de conocer la historia natural de la enfermedad, y el “punto crítico de irreversabilidad” (el tiempo en que es oportuno hacer el diagnóstico precoz de forma que permita un mejor curso de la enfermedad por la pronta intervención). En síntesis, sólo a veces “más vale curar que prevenir”, y en todo caso las actividades preventivas deberían ser vistas por el clínico con la misma exigencia de fundamento científico que las actividades curativas

The concept of prevention is surrounded by a halo of optimism that can sometimes confuse, since it is not always borne out by the facts. The saying, “An ounce of prevention is worth a pound of cure”, is not always true. Moreover, preventive activities should be based on a much more solid scientific basis than curative activities, since we offer the former as an option, whereas we are required to provide the latter. This article reviews two examples of paediatric screening instruments-one for neuroblastoma, and the other for hip dysplasia-which provide an opportunity to evaluate the practical problems of secondary prevention. These two instruments are used to examine a few general but important issues in screening, such as the need to know the natural history of the disease, and the “point of no return” (the moment past which early diagnosis and early intervention are no longer so effective in improving the course of the disease). In conclusion, only sometimes “an ounce of cure is worth a pound of prevention”, and regardless of the value of a given screening instrument, clinicians should use the same level of scientific rigor to judge preventive activities as they use for curative activities

Uso y abuso del poder médico para definir enfermedad y factor de riesgo, en relación con la prevención cuaternaria / Limits to the power of medicine to define disease and risk factor, and quarternary prevention

La seguridad del paciente implica evitar daños innecesarios como consecuencia de la actividad sanitaria. La prevención cuaternaria es la actividad médica que evita o atenúa las consecuencias de la actividad innecesaria o excesiva del sistema sanitario. Cuando los médicos definen enfermedad, factor de riesgo y salud, se justifican muchas intervenciones médicas innecesarias. Por ello, es clave mantener prudentemente controlada una visión tecnológica que facilita el intervencionismo médico. El poder médico de definir los límites de la salud y de la enfermedad convierte la definición del factor de riesgo en una frontera que casi siempre se inclina hacia el lado de la enfermedad. Se precisan más investigaciones sobre la prevención cuaternaria, al tiempo que se necesita el desarrollo de esta actividad para que frene la implantación de pautas preventives y curativas, diagnósticas y terapéuticas de dudoso beneficio (AU)

Patient safety means to avoid unnecessary harm produces by health care activities. Quaternary prevention is a medical activity that try to avoid or decrease the health consequences of unnecessary or excesive health care. Physicians’ definition of health, risk factor and disease justify many unnecessary medical interventions. It is critical to control an excessive medical technological actitude that allows excesive medical interventions. The medical power of definition of health and disease transform risk factor in a border which usually overlap with the disease field. We need research on quaternary prevention, and to develop activities of quaternary prevention which help in stopping the dissemination of health care (preventive, curative, diagnostic or therapeutic) of little value (AU)

Réplica de los autores. Metabolismo glucídico en la hipertensión arterial: papel de la sobrecarga oral de la glucosa / Autor’s response. Abnormal glycemic metabolism in essential hypertension. Role of the oral glucose tolerance test

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