Dorsal and median raphe neuronal firing dynamics characterized by nonlinear measures.

The dorsal (DRN) and median (MRN) raphe are important nuclei involved in similar functions, including mood and sleep, but playing distinct roles. These nuclei have a different composition of neuronal types and set of neuronal connections, which among other factors, determine their neuronal dynamics. Most works characterize the neuronal dynamics using classic measures, such as using the average spiking frequency (FR), the coefficient of variation (CV), and action potential duration (APD). In the current study, to refine the characterization of neuronal firing profiles, we examined the neurons within the raphe nuclei. Through the utilization of nonlinear measures, our objective was to discern the redundancy and complementarity of these measures, particularly in comparison with classic methods. To do this, we analyzed the neuronal basal firing profile in both nuclei of urethane-anesthetized rats using the Shannon entropy (Bins Entropy) of the inter-spike intervals, permutation entropy of ordinal patterns (OP Entropy), and Permutation Lempel-Ziv Complexity (PLZC). Firstly, we found that classic (i.e., FR, CV, and APD) and nonlinear measures fail to distinguish between the dynamics of DRN and MRN neurons, except for the OP Entropy. We also found strong relationships between measures, including the CV with FR, CV with Bins entropy, and FR with PLZC, which imply redundant information. However, APD and OP Entropy have either a weak or no relationship with the rest of the measures tested, suggesting that they provide complementary information to the characterization of the neuronal firing profiles. Secondly, we studied how these measures are affected by the oscillatory properties of the firing patterns, including rhythmicity, bursting patterns, and clock-like behavior. We found that all measures are sensitive to rhythmicity, except for the OP Entropy. Overall, our work highlights OP Entropy as a powerful and useful quantity for the characterization of neuronal discharge patterns.

Diseño de un panel de indicadores para programas de optimización del uso de antimicrobianos en los Servicios de Urgencias / Design of a panel of indicators for antibiotic stewardship programs in the Emergency Department

Objetivo: desarrollar un panel de indicadores para monitorizar la actividad de los programas de optimización del uso de antimicrobianos en los servicios de urgencias. Métodos: un grupo multidisciplinar formado por expertos en el manejo de la infección en urgencias y en la implantación de programas de optimización de uso de antimicrobianos (PROA) evaluó una propuesta de indicadores utilizando una metodología Delphi modificada. En una primera ronda, cada uno de los expertos clasificó la relevancia de cada indicador propuesto en 2 dimensiones (repercusión asistencial y facilidad de implantación) y 2 atributos (nivel de priorización y periodicidad de medida). La segunda ronda se realizó a partir del cuestionario modificado de acuerdo con las sugerencias planteadas y nuevos indicadores sugeridos por los participantes. Los expertos efectuaron modificaciones en el orden de priorización y calificaron los nuevos indicadores propuestos de la misma manera que en la primera ronda. Resultados: se propusieron un total de 61 potenciales indicadores divididos en 4 grupos: indicadores de consumo, microbiológicos, de proceso y de resultado. Tras el análisis de las puntuaciones y los comentarios realizados en la primera ronda, 31 indicadores fueron clasificados como de alta prioridad, 25 de prioridad intermedia y 5 de baja prioridad. Además se generaron 19 nuevos indicadores. Tras la segunda ronda, se mantuvieron los 61 indicadores inicialmente propuestos y adicionalmente se incorporaron 18 nuevos: 11 como de alta prioridad, 3 como de intermedia y 4 como de baja prioridad. Conclusiones: los expertos consensuaron un panel de indicadores PROA adaptado a los servicios de urgencias priorizados por nivel de relevancia como un elemento de ayuda para el desarrollo de estos programas, que contribuirá a monitorizar la adecuación del uso de antimicrobianos en estas unidades.(AU)

Objective: To develop a panel of indicators to monitor antimicrobial stewardship programs activity in the emergency department. Methods: A multidisciplinary group consisting of experts in the management of infection in emergency departments and the implementation of antimicrobial stewardship programs (ASP) evaluated a proposal of indicators using a modified Delphi methodology. In the first round, each expert classified the relevance of each proposed indicators in two dimensions (healthcare impact and ease of implementation) and two attributes (prioritization level and frequency). The second round was conducted based on the modified questionnaire according to the suggestions raised and new indicators suggested. Experts modified the prioritization order and rated the new indicators in the same manner as in the first round. Results: 61 potential indicators divided into four groups were proposed: consumption indicators, microbiological indicators, process indicators, and outcome indicators. After analyzing the scores and comments from the first round, 31 indicators were classified as high priority, 25 as intermediate priority, and 5 as low priority. Moreover, 18 new indicators were generated. Following the second round, all 61 initially proposed indicators were retained, and 18 new indicators were incorporated: 11 classified as high priority, 3 as intermediate priority, and 4 as low priority. Conclusions: The experts agreed on a panel of ASP indicators adapted to the emergency services prioritized by level of relevance. This is as a helpful tool for the development of these programs and will contribute to monitoring the appropriateness of the use of antimicrobials in these units.(AU)

Design of a panel of indicators for antibiotic stewardship programs in the Emergency Department / Diseño de un panel de indicadores para programas de optimización del uso de antimicrobianos en los Servicios de Urgencias

Objetivo: desarrollar un panel de indicadores para monitorizar la actividad de los programas de optimización del uso de antimicrobianos en los servicios de urgencias. Métodos: un grupo multidisciplinar formado por expertos en el manejo de la infección en urgencias y en la implantación de programas de optimización de uso de antimicrobianos (PROA) evaluó una propuesta de indicadores utilizando una metodología Delphi modificada. En una primera ronda, cada uno de los expertos clasificó la relevancia de cada indicador propuesto en 2 dimensiones (repercusión asistencial y facilidad de implantación) y 2 atributos (nivel de priorización y periodicidad de medida). La segunda ronda se realizó a partir del cuestionario modificado de acuerdo con las sugerencias planteadas y nuevos indicadores sugeridos por los participantes. Los expertos efectuaron modificaciones en el orden de priorización y calificaron los nuevos indicadores propuestos de la misma manera que en la primera ronda. Resultados: se propusieron un total de 61 potenciales indicadores divididos en 4 grupos: indicadores de consumo, microbiológicos, de proceso y de resultado. Tras el análisis de las puntuaciones y los comentarios realizados en la primera ronda, 31 indicadores fueron clasificados como de alta prioridad, 25 de prioridad intermedia y 5 de baja prioridad. Además se generaron 19 nuevos indicadores. Tras la segunda ronda, se mantuvieron los 61 indicadores inicialmente propuestos y adicionalmente se incorporaron 18 nuevos: 11 como de alta prioridad, 3 como de intermedia y 4 como de baja prioridad. Conclusiones: los expertos consensuaron un panel de indicadores PROA adaptado a los servicios de urgencias priorizados por nivel de relevancia como un elemento de ayuda para el desarrollo de estos programas, que contribuirá a monitorizar la adecuación del uso de antimicrobianos en estas unidades.(AU)

Objective: To develop a panel of indicators to monitor antimicrobial stewardship programs activity in the emergency department. Methods: A multidisciplinary group consisting of experts in the management of infection in emergency departments and the implementation of antimicrobial stewardship programs (ASP) evaluated a proposal of indicators using a modified Delphi methodology. In the first round, each expert classified the relevance of each proposed indicators in two dimensions (healthcare impact and ease of implementation) and two attributes (prioritization level and frequency). The second round was conducted based on the modified questionnaire according to the suggestions raised and new indicators suggested. Experts modified the prioritization order and rated the new indicators in the same manner as in the first round. Results: 61 potential indicators divided into four groups were proposed: consumption indicators, microbiological indicators, process indicators, and outcome indicators. After analyzing the scores and comments from the first round, 31 indicators were classified as high priority, 25 as intermediate priority, and 5 as low priority. Moreover, 18 new indicators were generated. Following the second round, all 61 initially proposed indicators were retained, and 18 new indicators were incorporated: 11 classified as high priority, 3 as intermediate priority, and 4 as low priority. Conclusions: The experts agreed on a panel of ASP indicators adapted to the emergency services prioritized by level of relevance. This is as a helpful tool for the development of these programs and will contribute to monitoring the appropriateness of the use of antimicrobials in these units.(AU)

Noribogaine acute administration in rats promotes wakefulness and suppresses REM sleep.

Ibogaine is a potent atypical psychedelic that has gained considerable attention due to its antiaddictive and antidepressant properties in preclinical and clinical studies. Previous research from our group showed that ibogaine suppresses sleep and produces an altered wakefulness state, which resembles natural REM sleep. However, after systemic administration, ibogaine is rapidly metabolized to noribogaine, which also shows antiaddictive effects but with a distinct pharmacological profile, making this drug a promising therapeutic candidate. Therefore, we still ignore whether the sleep/wake alterations depend on ibogaine or its principal metabolite noribogaine. To answer this question, we conducted polysomnographic recordings in rats following the administration of pure noribogaine. Our results show that noribogaine promotes wakefulness while reducing slow-wave sleep and blocking REM sleep, similar to our previous results reported for ibogaine administration. Thus, we shed new evidence on the mechanisms by which iboga alkaloids work in the brain.

Speech-induced suppression during natural dialogues.

When engaged in a conversation, one receives auditory information from the other's speech but also from their own speech. However, this information is processed differently by an effect called Speech-Induced Suppression. Here, we studied brain representation of acoustic properties of speech in natural unscripted dialogues, using electroencephalography (EEG) and high-quality speech recordings from both participants. Using encoding techniques, we were able to reproduce a broad range of previous findings on listening to another's speech, and achieving even better performances when predicting EEG signal in this complex scenario. Furthermore, we found no response when listening to oneself, using different acoustic features (spectrogram, envelope, etc.) and frequency bands, evidencing a strong effect of SIS. The present work shows that this mechanism is present, and even stronger, during natural dialogues. Moreover, the methodology presented here opens the possibility of a deeper understanding of the related mechanisms in a wider range of contexts.

Characterization of content associated with lesbian, gay, bisexual, transgender, intersex, and queer individuals in Chilean medical schools: a cross-sectional survey.

BACKGROUND: Lesbian, gay, bisexual, transgender, intersex, queer, and other sexual and gender identities (LGBTIQ+) individuals face health inequities. Additionally, medical students report a lack of confidence in providing specific health care to LGBTIQ + individuals, and medical schools do not offer the breadth and depth of coverage needed to fully prepare and make them comfortable in caring for these individuals. This study aims to characterize the teaching of curricular content related to LGBTIQ + health issues in medical schools in Chile. METHODS: This was a cross-sectional descriptive mixed-methods study based on a 15-question survey sent to school directors of the 24 medical schools in Chile, conducted between October 2020 and July 2021. The questions included in the study were mostly based on two pre-existing questionnaires covering content, assessment methods, and identification of barriers to teaching this content. RESULTS: The validated questionnaire was answered by 14 of 24 Chilean medical schools, with 11 schools (78.9%) declaring that they included some training in their curriculum. The predominant range of time allocated to LGBTIQ + training in medical programs was between 1 and 5 h. The most addressed topics were HIV (92.85%), sexual orientation (78.57%), and chronic disease risk in LGBTIQ + populations (78.57%). Most schools, accounting for 71.5%, considered the content they delivered to be "moderately insufficient" or "insufficient". Regarding the teaching methodologies, the most used were lectures (92.8%), clinical cases (42.9%), and clinical simulation (28.6%). CONCLUSION: Most surveyed medical schools reported curricular spaces dedicated to teaching health issues of LGBTIQ + individuals, primarily during the pre-internship training period. However, the time allocated is insufficient, and there is little approach to topics beyond the patient's sexual history or sexual orientation. Given the crucial role of medical schools, they must adopt both local and national strategies to enrich training focused on the care of LGBTIQ + patients.

5-HT2A Receptor Knockout Mice Show Sex-Dependent Differences following Acute Noribogaine Administration.

Noribogaine (noribo) is the primary metabolite from ibogaine, an atypical psychedelic alkaloid isolated from the root bark of the African shrub Tabernanthe iboga. The main objective of this study was to test the hypothesis that molecular, electrophysiological, and behavioral responses of noribo are mediated by the 5-HT2A receptor (5-HT2AR) in mice. In that regard, we used male and female, 5-HT2AR knockout (KO) and wild type (WT) mice injected with a single noribo dose (10 or 40 mg/kg; i.p.). After 30 min., locomotor activity was recorded followed by mRNA measurements by qPCR (immediate early genes; IEG, glutamate receptors, and 5-HT2AR levels) and electrophysiology recordings of layer V pyramidal neurons from the medial prefrontal cortex. Noribo 40 decreased locomotion in male, but not female WT. Sex and genotype differences were observed for IEG and glutamate receptor expression. Expression of 5-HT2AR mRNA increased in the mPFC of WT mice following Noribo 10 (males) or Noribo 40 (females). Patch-clamp recordings showed that Noribo 40 reduced the NMDA-mediated postsynaptic current density in mPFC pyramidal neurons only in male WT mice, but no effects were found for either KO males or females. Our results highlight that noribo produces sexually dimorphic effects while the genetic removal of 5HT2AR blunted noribo-mediated responses to NMDA synaptic transmission.

Design of a panel of indicators for antibiotic stewardship programs in the Emergency Department. / Diseño de un panel de indicadores para programas de optimización del uso de antimicrobianos en los Servicios de Urgencias.

OBJECTIVE: To develop a panel of indicators to monitor antimicrobial stewardship programs activity in the emergency department. METHODS: A multidisciplinary group consisting of experts in the management of infection in emergency departments and the implementation of antimicrobial stewardship programs (ASP) evaluated a proposal of indicators using a modified Delphi methodology. In the first round, each expert classified the relevance of each proposed indicators in two dimensions (healthcare impact and ease of implementation) and two attributes (prioritization level and frequency). The second round was conducted based on the modified questionnaire according to the suggestions raised and new indicators suggested. Experts modified the prioritization order and rated the new indicators in the same manner as in the first round. RESULTS: 61 potential indicators divided into four groups were proposed: consumption indicators, microbiological indicators, process indicators, and outcome indicators. After analyzing the scores and comments from the first round, 31 indicators were classified as high priority, 25 as intermediate priority, and 5 as low priority. Moreover, 18 new indicators were generated. Following the second round, all 61 initially proposed indicators were retained, and 18 new indicators were incorporated: 11 classified as high priority, 3 as intermediate priority, and 4 as low priority. CONCLUSIONS: The experts agreed on a panel of ASP indicators adapted to the emergency services prioritized by level of relevance. This is as a helpful tool for the development of these programs and will contribute to monitoring the appropriateness of the use of antimicrobials in these units.

[Translated article] Design of a panel of indicators for antibiotic stewardship programs in the Emergency Department.

OBJECTIVE: To develop a panel of indicators to monitor antimicrobial stewardship programs activity in the emergency department. METHODS: A multidisciplinary group consisting of experts in the management of infection in emergency departments and the implementation of antimicrobial stewardship programs (ASP) evaluated a proposal of indicators using a modified Delphi methodology. In the first round, each expert classified the relevance of each proposed indicators in two dimensions (healthcare impact and ease of implementation) and two attributes (prioritisation level and frequency). The second round was conducted based on the modified questionnaire according to the suggestions raised and new indicators suggested. Experts modified the prioritisation order and rated the new indicators in the same manner as in the first round. RESULTS: 61 potential indicators divided into four groups were proposed: consumption indicators, microbiological indicators, process indicators, and outcome indicators. After analysing the scores and comments from the first round, 31 indicators were classified as high priority, 25 as intermediate priority, and 5 as low priority. Moreover, 18 new indicators were generated. Following the second round, all 61 initially proposed indicators were retained, and 18 new indicators were incorporated: 11 classified as high priority, 3 as intermediate priority, and 4 as low priority. CONCLUSIONS: The experts agreed on a panel of ASP Indicators adapted to the emergency services prioritised by level of relevance. This is as a helpful tool for the development of these programs and will contribute to monitoring the appropriateness of the use of antimicrobials in these units.

Immunological and senescence biomarker profiles in patients after spontaneous clearance of hepatitis C virus: gender implications for long-term health risk.

BACKGROUND: About 25% of patients with acute hepatitis C virus (HCV) infection show spontaneous clearance within the first six months of infection but may remain at risk of inflammaging, aging, and liver and non-liver disease complications. This study evaluated the differences in the plasma levels of immune checkpoints (ICs) and senescence-associated secretory phenotype (SASP) biomarkers between patients who had spontaneously eliminated HCV infection (SC group) and individuals without evidence of HCV infection (C group). METHODS: We performed a multicenter retrospective study of 56 individuals: 32 in the SC and 24 in the C groups. ICs and SASP proteins were analyzed using a Luminex 200TM analyzer. The statistical analysis used Generalized Linear Models with gamma distribution (log-link) adjusted by significant variables and sex. RESULTS: 13 ICs (BTLA, CD137(4-1BB), CD27, CD28, CD80, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, and TIM-3) and 13 SASP proteins (EGF, Eotaxin, IL-1alpha, IL-1RA, IL-8, IL-13, IL-18, IP-10, SDF-1alpha, HGF, beta-NGF, PLGF-1, and SCF) were significantly higher in SC group after approximately more than two years of HCV clearance. After stratifying by sex, differences remained significant for males, which showed higher levels for 13 ICs and 4 SASP proteins in SC. While only PD-L2 was significantly higher in SC women, and no differences in SASP were found. CONCLUSIONS: Higher plasma levels of different IC and SASP proteins were found in individuals after more than two years of HCV clearance, mainly in men. Alterations in these molecules might be associated with an increased risk of developing liver and non-hepatic diseases.

Sleep disrupts complex spiking dynamics in the neocortex and hippocampus.

Neuronal interactions give rise to complex dynamics in cortical networks, often described in terms of the diversity of activity patterns observed in a neural signal. Interestingly, the complexity of spontaneous electroencephalographic signals decreases during slow-wave sleep (SWS); however, the underlying neural mechanisms remain elusive. Here, we analyse in-vivo recordings from neocortical and hippocampal neuronal populations in rats and show that the complexity decrease is due to the emergence of synchronous neuronal DOWN states. Namely, we find that DOWN states during SWS force the population activity to be more recurrent, deterministic, and less random than during REM sleep or wakefulness, which, in turn, leads to less complex field recordings. Importantly, when we exclude DOWN states from the analysis, the recordings during wakefulness and sleep become indistinguishable: the spiking activity in all the states collapses to a common scaling. We complement these results by implementing a critical branching model of the cortex, which shows that inducing DOWN states to only a percentage of neurons is enough to generate a decrease in complexity that replicates SWS.

Fatigue as a key human factor in complex sociotechnical systems: Vessel Traffic Services.

Background: Vessel Traffic Services (VTS) are considered a subsystem of people, whose mission is to improve the effectiveness and efficiency of maritime transport within the maritime system. VTS operate as a control system where Vessel Traffic Services Operators (VTSOs) must cope with a complex environment to make up for safe and efficient maritime transport, so it is essential to understand how these operators maintain control through adapting to the uncertain and dynamic environment of maritime traffic. This multidisciplinary study explores how human factors within this complex sociotechnical system, means VTS, play a role in maritime safety, specifically focusing on fatigue, which is considered a key variable for VTSOs' performance. In this context, the research has focused on the assessment of fatigue with psychological and operational instruments to highlight the importance of the human element in CSSs. Objective: To study the intra and inter-individual differences in fatigue ratings and their relationships with other personal and environmental variables: mental workload, work shifts, reaction time, and hours of usual sleep. Methods: The study was conducted in two of the 19 Spanish Maritime Rescue Coordination Centers (MRCCs) with a sample of 23 active VTSOs (82.14% of the staff). Both objective and standardized subjective measures were used to assess fatigue and associated sleepiness (Borg RPE, Nasa-TLX, Stanford Sleepiness Scale, and Self-Assessment Manikin Scale). Results: A significant positive correlation between fatigue and mental workload was found, being more prevalent in the night shift, which shows a bigger variation in these variables. A significant difference was found in the increase in fatigue experienced throughout the shift depending on the hours of usual sleep, being smaller in the group of subjects reporting to sleep more. Conclusion: The human element is key to maritime safety related to Vessel Traffic Services, so it is of paramount importance to consider certain measures to counteract the negative effects of fatigue. A proper organization of duties on/off periods, assessment of work and rest schedules, and the implementation of fatigue management programs based on sleep education are recommended.

Voltammetric Kinetic Studies of Electrode Reactions: Guidelines for Detailed Understanding of Their Fundamentals.

Theoretical and practical foundations of basic electrochemical concepts of heterogeneous charge transfer reactions that underline electrochemical processes are presented for their detailed study by undergraduate and postgraduate students. Several simple methods for calculating key variables, such as the half-wave potential, limiting current, and those implied in the kinetics of the process, are explained, discussed, and put in practice through simulations making use of an Excel document. The current-potential response of electron transfer processes of any kinetics (i.e., any degree of reversibility) are deduced and compared for electrodes of different size, geometry, and dynamics, namely: static macroelectrodes in chronoamperometry and normal pulse voltammetry, and static ultramicroelectrodes and rotating disc electrodes in steady state voltammetry. In all cases, a universal, normalized current-potential response is obtained in the case of reversible (fast) electrode reactions, whereas this is not possible for nonreversible processes. For this last situation, different widely used protocols for the determination of the kinetic parameters (the mass-transport corrected Tafel analysis and the Koutecký-Levich plot) are deduced, proposing learning activities that highlight the foundations and limitations of such protocols, as well as the influence of the mass transport conditions. Discussions on the implementation of this framework and on the benefits and difficulties found are also presented.

Mechanisms and functions of respiration-driven gamma oscillations in the primary olfactory cortex.

Gamma oscillations are believed to underlie cognitive processes by shaping the formation of transient neuronal partnerships on a millisecond scale. These oscillations are coupled to the phase of breathing cycles in several brain areas, possibly reflecting local computations driven by sensory inputs sampled at each breath. Here, we investigated the mechanisms and functions of gamma oscillations in the piriform (olfactory) cortex of awake mice to understand their dependence on breathing and how they relate to local spiking activity. Mechanistically, we find that respiration drives gamma oscillations in the piriform cortex, which correlate with local feedback inhibition and result from recurrent connections between local excitatory and inhibitory neuronal populations. Moreover, respiration-driven gamma oscillations are triggered by the activation of mitral/tufted cells in the olfactory bulb and are abolished during ketamine/xylazine anesthesia. Functionally, we demonstrate that they locally segregate neuronal assemblies through a winner-take-all computation leading to sparse odor coding during each breathing cycle. Our results shed new light on the mechanisms of gamma oscillations, bridging computation, cognition, and physiology.

The cerebral cortex is the most recently evolved region of the mammalian brain. There, millions of neurons can synchronize their activity to create brain waves, a series of electric rhythms associated with various cognitive functions. Gamma waves, for example, are thought to be linked to brain processes which require distributed networks of neurons to communicate and integrate information. These waves were first discovered in the 1940s by researchers investigating brain areas involved in olfaction, and they are thought to be important for detecting and recognizing smells. Yet, scientists still do not understand how these waves are generated or what role they play in sensing odors. To investigate these questions, González et al. used a battery of computational approaches to analyze a large dataset of brain activity from awake mice. This revealed that, in the cortical region dedicated to olfaction, gamma waves arose each time the animals completed a breathing cycle ­ that is, after they had sampled the air by breathing in. Each breath was followed by certain neurons relaying olfactory information to the cortex to activate complex cell networks; this included circuits of cells known as feedback interneurons, which can switch off weakly activated neurons, including ones that participated in activating them in the first place. The respiration-driven gamma waves derived from this 'feedback inhibition' mechanism. Further work then examined the role of the waves in olfaction. Smell identification relies on each odor activating a unique set of cortical neurons. The analyses showed that gamma waves acted to select and amplify the best set of neurons for representing the odor sensed during a sniff, and to quieten less relevant neurons. Loss of smell is associated with many conditions which affect the brain, such as Alzheimer's disease or COVID-19. By shedding light on the neuronal mechanisms that underpin olfaction, the work by González et al. could help to better understand how these impairments emerge, and how the brain processes other types of complex information.

Precisión y fiabilidad de la medición del índice tobillo-brazo utilizando un dispositivo oscilométrico versus el método Doppler / Accuracy and reliability of ankle-brachial index measurement using an oscillometric device versus the Doppler method

Introducción: la medición del índice tobillo-brazo (ITB) es una prueba de primera línea y con alta precisión diagnóstica para detectar la enfermedad vascular periférica (EVP). El método Doppler, considerado el estándar de oro, requiere del dispositivo y de un operador capacitado, lo que limita su uso en la atención primaria. Como alternativa, un método oscilométrico que emplea un dispositivo de presión arterial automático es una prueba simple y accesible que podría minimizar los sesgos del observador y eliminar la necesidad de capacitación especial. Objetivos: validar la capacidad diagnóstica de un dispositivo oscilométrico automatizado frente al método Doppler para la medición del ITB. Materiales y métodos: se incluyeron pacientes con diabetes mellitus tipo 1 y 2 (DM1 y DM2), mayores de 50 años, con uno o más factores de riesgo cardiovascular. Luego de que los pacientes permanecieran 5 minutos acostados, se registró la presión arterial sistólica (PAS) con tensiómetro Welch Allyn DS 45-11 y Doppler Vascular Contec Sonoline B 8 Mhz en ambas arterias tibiales posteriores y en arteria braquial derecha. Posteriormente se realizaron los mismos registros con monitor de presión arterial automático modelo Omrom HEM-7130. Se calculó el ITB de cada miembro inferior y las capacidades diagnósticas (sensibilidad [S-, especificidad [E], concordancia por coeficiente kappa, valor predictivo positivo [VPP] y valor predictivo negativo [VPN]) del método oscilométrico para detectar un ITB patológico por Doppler (≤0,90). Resultados: se evaluaron 66 pacientes, 52 varones y 14 mujeres, 7 con DM1 y 59 con DM2, 69 años de edad (DS 9,8), con una antigüedad de la DM de 18,05 años (DS 12,01). La prevalencia de EVP detectada por Doppler (ITB ≤0,90) fue del 16,7% (IC 95% 9,9-23,4). El método oscilométrico para detectar un ITB ≤0,90 por Doppler mostró una S del 72,7% (IC 95% 51,8-93,6), una E del 96,3% (IC 95% 92,4-100), una concordancia del 92,4% (IC 95% 87,5-97,3), un VPP del 80,0% (IC 95% 59,9-100) y un VPN del 94,6% (IC 95% 90,0-99,3). Conclusiones: el alto VPN hallado (condición esencial para un método de screening) significa que si el método oscilométrico da un ITB >0,90, hay un 94,6% de posibilidad de que el ITB por Doppler no sea ≤0,90. El VPP de 80% encontrado significa que si el ITB oscilométrico es ≤0,90, hay un 80% de posibilidad de que el ITB Doppler sea verdaderamente ≤0,90. Por lo tanto, consideramos que la simple medición del ITB con el método oscilométrico podría recomendarse en la atención primaria, donde se requieren métodos rápidos, fáciles y confiables.

Introduction: the measurement of the ankle-brachial index (ABI) is a first-line test with high diagnostic accuracy for the detection of peripheral vascular disease. The Doppler method, considered the gold standard, requires the device and a trained operator, which limits its use in primary care. Alternatively, an oscillometric method using an automated blood pressure device is a simple and affordable test that could minimize observer bias and eliminate the need for special training. Objectives: to validate the diagnostic capacity of an automated oscillometric device against the Doppler method for ABI measurement. Materials and methods: diabetes mellitus type 1 and 2 (DM1 and DM2) patients older than 50 years with 1 or more cardiovascular risk factors were included. After 5 minutes lying down, SBP was recorded with a Welch Allyn DS 45-11 sphygmomanometer and Contec Sonoline B 8 Mhz Vascular Doppler in both posterior tibial arteries and in the right brachial artery. Subsequently, the same recordings were made with an Automatic Blood Pressure Monitor Model Omrom HEM-7130. The ABI of each lower limb and the diagnostic capabilities (sensitivity [S], specificity [E], concordance by kappa coefficient, positive predictive value [PPV] and negative predictive value [NPV] of the oscillometric method to detect a pathological ABI were calculated by Doppler (≤0.90). Results: 66 patients were evaluated, 52 men and 14 women, 7 DM1 and 59 DM2, 69 years old (SD 9.8) with a history of diabetes of 18.05 years (SD 12.01). The prevalence of PVD detected by Doppler (ABI ≤0.90) was 16.7% (95% CI 9.9-23.4). The oscillometric method to detect an ABI ≤0.90 by Doppler showed an S of 72.7% (95% CI 51.8-93.6), an E of 96.3% (95% CI 92.4-100), a concordance of 92.4% (95% CI 87.597.3), a PPV of 80.0% (95% CI 59.9-100) and a NPV of 94.6% (95% CI 90 .0-99.3). Conclusions: the high NPV found (essential condition for a screening method) means that if the oscillometric method gives an ABI >0.90, there is a 94.6% chance that the Doppler ABI is not ≤0.90. The PPV of 80% found means that if the oscillometric ABI is ≤0.90, there is an 80% chance that the Doppler ABI is truly ≤0.90. Therefore, we consider that the simple measurement of ABI with the oscillometric method could be recommended in primary care, where fast, easy and reliable methods are adequate.

Breathing modulates gamma synchronization across species.

Nasal respiration influences brain dynamics by phase-entraining neural oscillations at the same frequency as the breathing rate and by phase-modulating the activity of faster gamma rhythms. Despite being widely reported, we still do not understand the functional roles of respiration-entrained oscillations. A common hypothesis is that these rhythms aid long-range communication and provide a privileged window for synchronization. Here we tested this hypothesis by analyzing electrocorticographic (ECoG) recordings in mice, rats, and cats during the different sleep-wake states. We found that the respiration phase modulates the amplitude of cortical gamma oscillations in the three species, although the modulated gamma frequency bands differed with faster oscillations (90-130 Hz) in mice, intermediate frequencies (60-100 Hz) in rats, and slower activity (30-60 Hz) in cats. In addition, our results also show that respiration modulates olfactory bulb-frontal cortex synchronization in the gamma range, in which each breathing cycle evokes (following a delay) a transient time window of increased gamma synchrony. Long-range gamma synchrony modulation occurs during quiet and active wake states but decreases during sleep. Thus, our results suggest that respiration-entrained brain rhythms orchestrate communication in awake mammals.

Stability-indicative and conformation-specific enzyme linked immunosorbent assay for analysis of recombinant human gamma interferon.

Recombinant human interferon gamma (rhIFN-γ) is a promising molecule for the treatment of several diseases. A pair of conformation-specific monoclonal antibodies (mAbs) against rhIFN-γ was selected from generated hybridoma cell lines to design a sensitive, stability-indicative, sandwich-type ELISA. The main assay parameters were optimized by the checkerboard method for the highest signal-to-noise ratio: assay buffer composition, coating buffer pH and composition, coating temperature-incubation time parameters, and coating mAb concentration and conjugate dilution. Detection and quantification limits were estimated between 0.019 and 0.078 ng/mL, respectively, and recovery values were from 92.03% to 98.40%. The coefficient of variation of intra-assay precision parameters ranged from 2.32% to 9.21% while the inter-analyst variation was between 4.70% and 10.63%, supporting the method's repeatability. The ELISA was specific for correctly folded and non-aggregated molecular species, as compared to intrinsic Trp fluorescence (chemical denaturation) and optical density at 340 nm (thermal aggregation), respectively. However, the method was not sensitive to the small C-terminal degradation of full-length rhIFN-γ1-144 (losses of 6-12 amino acid residues) as compared to results with mass spectrometry and gel electrophoresis. ELISA showed good correlation with rhIFN-γ antiviral biological activity. This method was applied to the stability evaluation of rhIFN-γ in physiological buffer at low concentrations using polypropylene and glass vials also in the presence of adsorption protectant excipients. Furthermore, ELISA could be adapted to other applications such as quantification of IFN-γ in serum samples, Mycobacterium tuberculosis diagnosis, etc.

Dispositivos cardíacos implantables y uso de resonancia magnética / Cardiac implantable devices and use of magnetic resonance / Dispositivos cardíacos implantáveis e utilização da ressonância magnética

El uso de la resonancia magnética (RM) en las distintas áreas de la medicina se ha expandido de manera significativa y de forma diaria se solicitan numerosos estudios. El hecho de que los resonadores pueden interaccionar con algunos objetos ha llevado a que históricamente se les niegue la realización de este estudio a pacientes portadores de dispositivos cardíacos porque se entiende que existen contraindicaciones absolutas. El avance de la tecnología de los dispositivos y la creciente evidencia publicada han cambiado este concepto. Nos proponemos revisar los mecanismos por los cuales un dispositivo implantable puede interactuar con el resonador y las implicancias clínicas que esto podría tener si las hubiera. La mayoría de los pacientes portadores de dispositivos cardíacos de estimulación podrán realizarse una RM, pero para que este procedimiento sea seguro es importante conocer las características y el tipo específico de dispositivo implantado. Proponemos finalmente puntos clave y algoritmos para tener en cuenta para el manejo adecuado de estos pacientes.

The use of magnetic resonance imaging (MRI) in different areas of medicine has expanded significantly and numerous procedures are indicated daily. The fact that resonators could interact with some objects has historically led to patients with cardiac devices being denied an MRI on the understanding that they suppose an absolute contraindication. Advances in device technology and the increasing evidence have changed this concept. We intend to review the mechanisms by which an implantable device could interact with the resonator and the clinical implications that this could have if any. Most patients will be able to undergo these studies, but to determine the safety of performing an MRI it is important to know the characteristics and specific type of implanted device. Finally, we provide key points and algorithms to take into account for these patients.

O uso da ressonância magnética em diferentes áreas da medicina tem se expandido significativamente e inúmeros exames são indicados diariamente. A possibilidade de que os ressonadores interajam com alguns objetos historicamente levou os pacientes com dispositivos cardíacos a terem a ressonância magnética negada por entender que existem contraindicações absolutas. Os avanços na tecnologia de dispositivos e o aumento das evidências publicadas mudaram esse conceito. Pretendemos revisar os mecanismos pelos quais um dispositivo implantável pode interagir com o ressonador e as implicações clínicas que isso pode ter, se houver. A grande maioria dos pacientes poderá se submeter a esses estudos, mas para determinar a segurança de realizar uma ressonância magnética é importante conhecer as características e o tipo específico de dispositivo implantado. Por fim, propomos pontos e algoritmos para a gestão dos pacientes.