GABA Neuron Alterations, Cortical Circuit Dysfunction and Cognitive Deficits in Schizophrenia

Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions

A Kalman rank condition for the localized distributed controllability of a class of linear parabolic systems

We present a generalization of the Kalman rank condition to the case of $n\times n$ linear parabolic systems with constant coefficients and diagonalizable diffusion matrix. To reach the result, we are led to prove a global Carleman estimate for the solutions of a scalar $2n-$order parabolic equation and deduce from it an observability inequality for our adjoint system

X-ray Spectra of the RIXOS source sample

We present results of an extensive study of the X-ray spectral properties of sources detected in the RIXOS survey, that is nearly complete down to a flux limit of 3e-14 cgs (0.5-2 keV). We show that for X-ray surveys containing sources with low count rate spectral slopes estimated using simple hardness ratios in the ROSAT band can be biased. Instead we analyse three-colour X-ray data using statistical techniques appropriate to the Poisson regime which removes the effects of this bias. We have then applied this technique to the RIXOS survey to study the spectral properties of the sample. For the AGN we find an average energy index of 1.05+-0.05 with no evidence for spectral evolution with redshift. Individual AGN are shown to have a range of properties including soft X-ray excesses and intrinsic absorption. Narrow Emission Line Galaxies also seem to fit to a power-law spectrum, which may indicate a non-thermal origin for their X-ray emission. We infer that most of the clusters in the sample have a bremsstrahlung temperature >3 keV, although some show evidence for a cooling flow. The stars deviate strongly from a power-law model but fit to a thermal model. Finally, we have analysed the whole RIXOS sample containing 1762 sources. We find that the mean spectral slope of the sources hardens at lower fluxes in agreement with results from other samples. However, a study of the individual sources demonstrates that the hardening of the mean is caused by the appearance of a population of very hard sources at the lowest fluxes. This has implications for the nature of the soft X-ray background.Comment: 31,LaTeX file, 2 PS files with Table 2 and 22 PS figures. MNRAS in pres

Comparative Analysis of Microbial Sensing Molecules in Mucosal Tissues with Aging

Host-bacterial interactions at mucosal surfaces require recognition of the bacteria by host cells enabling targeted responses to maintain tissue homeostasis. It is now well recognized that an array of host-derived pattern recognition receptors (PRRs), both cell-bound and soluble, are critical to innate immune engagement of microbes via microbial-associated molecular patterns (MAMP). This report describes the use of a nonhuman primate model to evaluate changes in the expression of these sensing molecules related to aging in healthy gingival tissues. Macaca mulatta aged 3-24 years were evaluated clinically and gingival tissues obtained, RNA isolated and microarray analysis conducted for gene expression of the sensing pattern recognition receptors (PRRs). The results demonstrated increased expression of various PRRs in healthy aging gingiva including extracellular (CD14, CD209, CLEC4E, TLR4), intracellular (NAIP, IFIH1, DAI) and soluble (PTX4, SAA1) PRRs. Selected PRRs were also correlated with both bleeding on probing (BOP) and pocket depth (PD) in the animals. These findings suggest that aged animals express altered levels of various PRRs that could affect the ability of the tissues to interact effectively with the juxtaposed microbial ecology, presumably contributing to an enhanced risk of periodontitis even in clinically healthy oral mucosal tissues with aging

Fast visible and extended nearinfrared multispectral fundus camera

We present a multispectral fundus camera that performs fast imaging of the ocular posterior pole in the visible and near-infrared (400 to 1300 nm) wavelengths through 15 spectral bands, using a flashlight source made of light-emitting diodes, and CMOS and InGaAs cameras. We investigate the potential of this system for visualizing occult and overlapping structures of the retina in the unexplored wavelength range beyond 900 nm, in which radiation can penetrate deeper into the tissue. Reflectance values at each pixel are also retrieved from the acquired images in the analyzed spectral range. The available spectroscopic information and the visualization of retinal structures, specifically the choroidal vasculature and drusen-induced retinal pigment epithelium degeneration, which are hardly visible in conventional color fundus images, underline the clinical potential of this system as a new tool for ophthalmic diagnosis.Peer ReviewedPostprint (published version

Stakeholders' Understanding of European Medicine Agency's COVID-19 Vaccine Information Materials in EU and Regional Contexts

The COVID-19 pandemic posed challenges to communicating accurate information about vaccines because of the spread of misinformation. The European Medicines Agency (EMA) tried to reassure the public by communicating early on about the development and approval of COVID-19 vaccines. The EMA surveyed patients/consumers, healthcare professional organizations, and individual stakeholders, both at the EU level and in an Italian regional context. The objectives of the study were to see if the EMA's core information materials were informative and well-understood and which communication channels were preferred by the public. The main findings showed that individual patients/consumers generally prefer to obtain information about COVID-19 vaccines from the internet or mass media, while organizations and individual healthcare professionals prefer to obtain information from national and international health authorities. Both at EU and local levels, participants had a good understanding of the key messages from regulators and found the materials useful and relevant. However, some improvements were recommended to the visual, text, and dissemination formats, including publishing more information on safety and using a more public-friendly language. Also, it was recommended to maintain the EMA's approach of using media, stakeholder engagement, and web-based formats to communicate about COVID-19 vaccines. In conclusion, user-testing of proactive communication materials aimed to prebunk misinformation during a public health crisis helps to ensure that users understand the development and safety of novel vaccine technologies. This information can then be used as a basis for further evidence-based communication activities by regulators and public health bodies in an emergency context

The Effect of the Spanish Nuclear Phase-out on the Electricity Market

Portugal and Spain are integrated into what is known as the Iberian Electricity Market. Spain participates in this market with significant contribution of energy produced by nuclear plants. In 2022, nuclear energy accounted for 22 % of the total energy generated in Spain. Nuclear power plants sell their energy largely through bilateral contracts, and approximately 20 % is offered in the day-ahead electricity market. By 2035, Spain will phase-out nuclear power producing a structural change of its generation mix. In this paper, we investigate the effect on the day-ahead Iberian electricity market that the gradual removal of nuclear power plants will have on the daily electricity market. The methodology is based on a ceteris paribus approach, where generation conditions are modified by removing nuclear plants and keeping the rest of the variables constant (demand and other generation). Under these conditions, the market is reproduced, estimating how electricity prices change in the day-ahead electricity market. To evaluate the market electricity prices under this new scenario with a total or a partial elimination of nuclear energy generation, it is necessary to use a market model. The existing literature shows various approaches to replicate the electricity market, among which are agent-base modelling, optimization algorithms, artificial intelligence techniques or metaheuristic merit-order methods. Our approach is based on the latter methods, by using actual generation and demand data, the new market generation and demand curves are reconstructed and the new clearing price is obtained. For the most conservative scenario, the results show a price increase of more than 5 % for the first 6 months of 2021. The reason for this increase is that nuclear generation participates in the market by offering its energy at prices close to zero. When this generation is withdrawn, there is a shift to the left of the hourly generation curve producing a new market equilibrium at a point of higher price and lower energy

Factors associated with mental health outcomes after COVID-19: a 24-month longitudinal follow-up study

Objetivo: Investigar la proporción de resultados de salud mental (MHO) y los factores asociados en los supervivientes del COVID-19 durante un periodo de seguimiento de 24 meses. Método: Se realizó un estudio observacional, prospectivo en un hospital universitario de Barranquilla, Colombia, desde el 1 de abril de 2020 hasta el 30 de agosto de 2022. Se reclutó una cohorte de 1565 sobrevivientes de COVID-19 después del alta de los servicios de urgencias (SU), piso de hospitalización (FI) y unidad de cuidados intensivos (UCI) y se les hizo seguimiento durante 24 -meses. La evaluación clínica incluyó escalas de detección de síntomas de ansiedad, depresión, trastorno de estrés postraumático (TEPT) e insomnio. También se recogieron factores sociodemográficos y clínicos para identificar posibles factores asociados. Se realizaron modelos descriptivos, bivariantes y lineales mixtos de efectos aleatorios. Resultados: Se incluyeron un total de 1565 pacientes, de los cuales 785 (50,35%) eran hombres. Se identificó una gran proporción de pacientes con síntomas mentales. Después de 24 meses, las proporciones de síntomas de ansiedad, depresión, TEPT e insomnio seguían siendo elevadas: 16,55%, 21,79%, 35,27% y 23,86%, respectivamente. Los factores sociales, la localización de las estancias hospitalarias, las comorbilidades físicas y la gravedad del COVID-19 se asociaron significativamente con los síntomas de ansiedad, depresión, TEPT e insomnio. Conclusiones: Se han documentado los efectos nocivos de la COVID-19 sobre la salud mental durante 2 años, así como las variables que influyen en estos resultados. Estos resultados deberían ayudar en el desarrollo de iniciativas de salud pública para reducir las tasas de morbilidad en pacientes post-COVID-19. 2023 Los autores.Objective: Investigate the proportion of mental health outcomes (MHOs) and associated factors in COVID-19 survivors during a 24-month follow-up period. Method: An observational, prospective study was performed in a teaching hospital in Barranquilla, Colombia, from April 1, 2020, to August 30, 2022. A cohort of 1565 COVID-19 survivors was recruited after discharge from the emergency room (ER), inpatient floor (IF), and intensive care unit (ICU) services and followed for 24 -months. The clinical assessment included screening scales for symptoms of anxiety, depressive, post-traumatic stress disorder (PTSD), and insomnia. Sociodemographic and clinical factors were also collected to identify possible associated factors. Descriptive, bivariate and mixed random-effect linear models were performed. Results: A total of 1565 patients were included, of whom 785 (50.35%) were men. A large proportion of patients with mental symptoms were identified. After 24-months, the proportions of anxiety, depression, PTSD, and insomnia symptoms remained high at 16.55%, 21.79%, 35.27%, and 23.86%, respectively. Social factors, location of hospital stays, physical comorbidities, and the severity of COVID-19 were significantly associated with anxiety, depression, PTSD, and insomnia symptoms. Conclusions: COVID-19's 2-year deleterious impacts on mental health, as well as the variables influencing these findings, have been documented. These results should aid in the development of public health initiatives to reduce morbidity rates in post-COVID-19 patients. © 2023 The Authors

Risk-based DC security assessment for future DC-independent system operator

—The use of multi-terminal HVDC to integrate wind power coming from the North Sea opens de door for a new transmission system model, the DC-Independent System Operator (DC-ISO). DC-ISO will face highly stressed and varying conditions that requires new risk assessment tools to ensure security of supply. This paper proposes a novel risk-based static security assessment methodology named risk-based DC security assessment (RB-DCSA). It combines a probabilistic approach to include uncertainties and a fuzzy inference system to quantify the systemic and individual component risk associated with operational scenarios considering uncertainties. The proposed methodology is illustrated using a multi-terminal HVDC system where the variability of wind speed at the offshore wind is included

Identifying and Exploring Jean Watson’s Theory of Human Caring in Nursing Approaches for Patients with Psychoactive Substance Dependence in Medical and Surgical Acute Wards

Patients with substance use disorders may view healthcare professionals as capable of supporting them through their suffering and experience. Although numerous studies have focused on the roles, approaches, and attitudes of healthcare professionals, there is a lack of information on the nursing perspective. This study aims to explore the experiences and nursing approaches towards patients with psychoactive substance dependence admitted to an Italian acute hospital ward. A qualitative phenomenological study was conducted. Data were collected using semi-structured face-to-face interviews. The interviews were transcribed, read thoroughly, and analysed. Fifteen nurses were interviewed. Six main themes were extracted: (1) origin context, (2) participants’ personal thoughts, (3) type of approach provided, (4) school education received on the topic, (5) effectiveness of rehabilitative therapy, and (6) methods that can improve nursing care. The findings suggest that most respondents experience stigma and discrimination when providing care to these patients. In response to the results obtained, models have been suggested, such as Jean Watson’s Human Caring Theory, which shows how practising a holistic approach based on empathy and active listening can improve the relationship between nurses and patients. Furthermore, to eliminate stereotypes, it would be appropriate to act on the university education of nurses. This study was not registered