Local wakefulness-like activity of layer 5 cortex under general anaesthesia.

Consciousness, defined as being aware of and responsive to one's surroundings, is characteristic of normal waking life and typically is lost during sleep and general anaesthesia. The traditional view of consciousness as a global brain state has evolved toward a more sophisticated interplay between global and local states, with the presence of local sleep in the awake brain and local wakefulness in the sleeping brain. However, this interplay is not clear for general anaesthesia, where loss of consciousness was recently suggested to be associated with a global state of brain-wide synchrony that selectively involves layer 5 cortical pyramidal neurons across sensory, motor and associative areas. According to this global view, local wakefulness of layer 5 cortex should be incompatible with deep anaesthesia, a hypothesis that deserves to be scrutinised with causal manipulations. Here, we show that unilateral chemogenetic activation of layer 5 pyramidal neurons in the sensorimotor cortex of isoflurane-anaesthetised mice induces a local state transition from slow-wave activity to tonic firing in the transfected hemisphere. This wakefulness-like activity dramatically disrupts layer 5 interhemispheric synchrony with mirror-image locations in the contralateral hemisphere, but does not reduce the level of unconsciousness under deep anaesthesia, nor in the transitions to/from anaesthesia. Global layer 5 synchrony may thus be a sufficient condition for anaesthesia-induced unconsciousness, but is not a necessary one, at least under isoflurane anaesthesia. Local wakefulness-like activity of layer 5 cortex can be induced and maintained under deep anaesthesia, encouraging further investigation into the local vs. global aspects of anaesthesia-induced unconsciousness. KEY POINTS: The neural correlates of consciousness have evolved from global brain states to a nuanced interplay between global and local states, evident in terms of local sleep in awake brains and local wakefulness in sleeping brains. The concept of local wakefulness remains unclear for general anaesthesia, where the loss of consciousness has been recently suggested to involve brain-wide synchrony of layer 5 cortical neurons. We found that local wakefulness-like activity of layer 5 cortical can be chemogenetically induced in anaesthetised mice without affecting the depth of anaesthesia or the transitions to and from unconsciousness. Global layer 5 synchrony may thus be a sufficient but not necessary feature for the unconsciousness induced by general anaesthesia. Local wakefulness-like activity of layer 5 neurons is compatible with general anaesthesia, thus promoting further investigation into the local vs. global aspects of anaesthesia-induced unconsciousness.

[Frequency and associated risk factors of cardiovascular autonomic neuropathy among patients with type 2 Diabetes.] / Frecuencia y factores de riesgo asociados de Neuropatía Autonómica Cardíaca en pacientes con Diabetes tipo 2.

Background: Cardiovascular autonomic neuropathy (CAN) is a common complication of diabetes and is associated with cardiovascular morbidity and mortality. Despite its prevalence, it is usually underdiagnosed. Objective to assess frequency of CAN in type 2 diabetes, treated at the Diabetology Service at Cordoba Hospital, Argentina. Method: Cross-sectional study was conducted from May 2015 to May 2016. Cardiovascular Autonomic Tests (Ewing´s battery) were performed: response to Valsalva maneuver, expiration-to-inspiration ratio (E/I ratio), standing to lying flat and postural hypotension. Results: 100 type 2 diabetes patients, 53% females. The mean age and diabetes duration 52 years old and 8.4 years, respectively. Hemoglobin A1c level of 8.7% and 47% were insulin-requiring type 2 diabetes patients. 29% had early CAN, 54% confirmed CAN (10% severe CAN) and 17% normal cardiovascular tests. Confirmed CAN was higher in those with longer duration of diabetes; longer duration of insulin therapy, older patients and severe hypoglycemia events was higher in those with confirmed CAN versus without CAN or early CAN (p 0.003). The risk factors associated were hypertension OR 2.55 (p 0.02), peripheral neuropathy OR 11.7 (p <0.0001), diabetic retinopathy OR 9.03 (p 0.001), diabetic nephropathy OR 3.12 (p 0.03) and hemoglobin A1c > 7% OR 2.57 (p 0, 03). Conclusions: frequency of CAN was high, was associated with hypertension, microvascular complications, older age, poor metabolic control, longer duration of disease and insulin therapy. Patients with a higher risk of developing CAN should be identified, in order to reduce the impact of this complication.

Introducción: La neuropatía autonómica cardíaca (NAC) es una complicación frecuente de la diabetes y aumenta la morbimortalidad cardiovascular. A pesar de su prevalencia e impacto está subdiagnosticada. Objetivo: Determinar la frecuencia de NAC y factores de riesgo asociados en pacientes con diabetes tipo 2(DM2), en el Servicio de Diabetología del Hospital Córdoba. Material y Métodos: estudio transversal, desde Mayo de 2015 a Mayo de 2016. Se realizó Test Autonómicos Cardiovasculares: Maniobra de Valsalva (MV), Respiración Profunda (RP), Razón 30/15 e Hipotensión ortostática. Resultados: Se reclutaron 100 pacientes con DM2. 53 % sexo femenino. Edad promedio 52 años, IMC 30,9; HbA1c 8,7 % y evolución de la enfermedad 8,4 años. El 17 % presentaron test normales. El 29 % tenía NAC temprana y 54% NAC confirmada (10 % NAC severa). Los pacientes con NAC confirmada tenían mayor tiempo de evolución (11 vs 5 años ), mayor duración de insulinoterapia (5 vs 1,5 años ), mayor edad ( 54 vs 49 años ) y mayor riesgo de hipoglucemias severas comparado con pacientes sin NAC o NAC temprana (p 0,003).Factores de riesgo asociados hipertensión arterial OR 2,55 (p 0,02), neuropatía periférica OR 11,7 (p<0,0001) , retinopatía OR 9,03 (p 0,001), nefropatía OR 3,12 (p 0,03) y HbA1c > 7% OR 2,57(p 0,03). Conclusiones: Hubo una alta frecuencia de NAC, se asoció con hipertensión, complicaciones microvasculares, mayor edad, duración de la enfermedad, de la insulinoterapia y mal control metabólico. Se debería identificar a pacientes con mayor riesgo, para reducir su aparición e impacto.

Factores de riesgo asociados al desarrollo del úlceras en pacientes con diabetes mellitus tipo 2: siete años de experiencia / Risk factors associated with the development of ulcers in patients with type 2 diabetes mellitus: seven years of experience

Introducción: las amputaciones de extremidades inferiores relacionadas con diabetes preceden de una úlcera del pie. Los factores de riesgo incluyen neuropatía, enfermedad vascular periférica, altas presiones plantares, trauma menor, ulceración o amputación previa y discapacidad visual. Objetivos: determinar los factores de riesgo relacionados con el desarrollo de úlcera del pie en pacientes diabéticos asistidos en la Unidad Provincial de Pie Diabético (UPPD) en el Hospital Córdoba, Argentina. Material y métodos: estudio transversal y descriptivo en adultos con diabetes mellitus tipo 2 (DM2) que consultaron en la UPPD entre julio de 2008 y julio de 2015