Novel modulatory effects of neurosteroids and benzodiazepines on excitatory and inhibitory neurons excitability: a multi-electrode array (MEA) recording study.

The dynamic equilibrium between glutamate- and GABA-mediated synaptic neurotransmission in the brain is fundamental to the control of nervous system function. Such a balance is regulated by the \u2018tonic\u2019 release of a variety of neurotransmitters and endogenous factors that influence synaptic function. One such important group of modulatory molecules are the neurosteroids (NSs) which, similarly to benzodiazepines (BDZs), enhance GABAergic neurotransmission. The purpose of our work was to investigate, at in-vivo physiologically relevant concentrations, the effects of these two classes of GABA modulators on dissociated neocortical neuron networks grown in long-term culture. We used a multi-electrode array (MEA) recording technique and a novel method of analysis that was able to both identify the action potentials of engaged excitatory and inhibitory neurons and to detect novel drug-induced network up-states (burst). We found that the NSs tetrahydrodeoxycorticosterone (THDOC) and allopregnanolone (ALLO) applied at low nanomolar concentrations, produced different modulatory effects on the two neuronal clusters. Conversely, at high concentrations (1 \ub5M), both NSs, decreased excitatory and inhibitory neuron cluster excitability; however, even several hours after washout, the excitability of inhibitory neurons continued to be depressed, leading to a network long term depression (LTD). The BDZs clonazepam (CLZ) and midazolam (MDZ) also decreased the network excitability, but only MDZ caused LTD of inhibitory neuron cluster. To investigate the origin of the LTD after MDZ application, we tested finasteride (FIN), an inhibitor of endogenous NSs synthesis. FIN did not prevent the LTD induced by MDZ, but surprisingly induced it after application of CLZ. The significance and possible mechanisms underlying these LTD effects of NSs and BDZs are discussed. Taken together, our results not only demonstrate that ex-vivo neuronal networks show a sensitivity to drugs comparable to that expressed in vivo, but also provide a new global in-vitro description of the physiological mode of action of NSs and BDZs that can help in understanding their activity in more complex systems

Mental disorders and work integration: a retrospective study in a northern italian town.

OBJECTIVES: THE PRESENT STUDY WAS CONDUCTED IN A VOCATIONAL INTEGRATION SERVICE OF A NORTHERN ITALIAN TOWN WITH TWO MAJOR AIMS: to assess vocational integration programs undertaken from 1(st) January 2004 to 1(st) January 2007; and to identify job tenure-associated predictors. METHODS: This is a retrospective study; we collected data such as gender, age, duration, type and outcome of the vocational integration program, and number of interventions performed by the vocational integration service. Self-report questionnaires were also used to assess the satisfaction of users, caregivers, practitioners, and of the company contacts involved in the study. RESULTS: The service has enrolled 84 users during the observation period. Out of these users, 64.3% of them still had their jobs after three years. Users, caregivers and company contacts expressed high levels of satisfaction for the support received by the vocational integration service. The company expressed less satisfaction for the collaboration received by the Departments of Mental Health (DMHs) that coached the users. The only variable associated to the outcome was the number of interventions that the users received before their placement on the job. CONCLUSIONS: Despite all the limits of this study, its results show that the chance of taking advantage of a supported job placement service has likely proven itself effective in helping people with mental disorders to obtain and maintain a competitive employment. Our results, however, also point to the necessity of implementing newer strategies meant to develop a greater integration among all services dealing with mentally ill people

Atypical “seizure-like” activity in cortical reverberating networks in vitro can be caused by LPS-induced inflammation: a multi-electrode array study from a hundred neurons

We show here that a mild sterile inflammation induced by the endotoxin lipopolysaccharide (LPS), in a neuron/astrocyte/microglial cortical network, modulates neuronal excitability and can initiate long-duration burst events resembling epileptiform seizures, a recognized feature of various central nervous neurodegenerative, neurological and acute systemic diseases associated with neuroinflammation. To study this action, we simultaneously analyzed the reverberating bursting activity of a hundred neurons by using in vitro multi-electrode array (MEA) methods. ~5 hours after LPS application, we observed a net increase in the average number of spikes elicited in engaged cells and within each burst, but no changes neither in spike waveforms nor in burst rate. This effect was characterized by a slow, two-fold exponential increase of the burst duration and the appearance of rarely occurring long-burst events that were never seen during control recordings. These changes and the time-course of microglia-released proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α), were blocked by pre-treatment with 50 nM minocycline, an established anti-inflammatory agent which was inactive when applied alone. Assay experiments also revealed that application of 60 pM exogenous TNF-α after 12-15 h, produced non-washable changes of neuronal excitability, completely different from those induced by LPS, suggesting that TNF-α release alone was not responsible for our observed findings. Our results indicate that the link between neuroinflammation and hyperexcitability can be unveiled by studying the long-term activity of in vitro neuronal/astrocyte/microglial networks

Hong Kong, China, and the Disruption of Antitrust

Under the “One Country, Two Systems” rule, Hong Kong and China maintain different legal systems. This dichotomy also applies in the antitrust context. China adopted its Anti-Monopoly Law in 2007, while Hong Kong waited until 2012 to introduce its Competition Ordinance (and another three years to fully implement it). This article compares the antitrust laws of these two jurisdictions and their enforcement in light of a turning point: the disruption caused by Big Tech. Interestingly, while the competition laws of Hong Kong and China are substantively similar to each other and to legal precedent in other jurisdictions, Hong Kong has adopted an adversarial system of enforcement, and China an administrative system. Through an analysis of recent antitrust developments in the two jurisdictions, this article shows the importance of agency independence, due process, and robust judicial scrutiny for the proper functioning of an administrative system of enforcement. This article also demonstrates that judicial scrutiny in an adversarial system needs the certainty of legal rules, particularly to clarify the burden of proof to be met by the competition authorities. In light of these findings, this article proposes a three-pronged competition and regulation approach for the scrutiny of Big Tech that does not water down the two principles of due process and robust judicial scrutiny. This is significant. The frustration with market concentration should not lead policymakers to propose changes to antitrust enforcement that could weaken these two principles and attribute a higher value to the speed of decision-making over the importance of a thorough analysis

Sustainability and EU merger control

This article analyses the role that sustainability plays within the current system of European merger control. Sustainability plays a role in market definition and market appraisal. The Commission has extended the boundaries of the analysis to consideration of innovation spaces within the context of harm to innovation competition as a theory of harm. Arguably, the rationale for doing so should be extended to considerations of efficiencies and failing firm defence. More could also be done in measuring sustainability, in cooperation with environmental and other agencies with a regulatory remit. Beyond this, changing the framework of merger control to assess the effects of mergers on sustainability may act as a Trojan horse for consideration of other non-market related factors, opening the door to undesirable consequences. Overall, the increasing consumer awareness of green products suggests that the preservation of competitive markets may be the best contribution to sustainability that merger control can bestow

Dynamic simulation of an integrated thermal electricity storage system using Aspen Plus Dynamics

openThe increment of greenhouse gas emissions from human activities have forced the world authorities to ratify stringent measures devoted to the reduction of primary energy consumption and to the spread of Renewable Energy Sources (RES). However, the widespread adoption of variable and intermittent RES highlights the necessity for large-scale energy storage, but available technologies, like Pumped Hydro, Compressed Air Energy Storage or Flow Batteries, suffer from geographical constraints, require fossil fuel streams or are characterized by low cycle life. In this context, Thermal Energy Storage Systems are poised to play a fundamental role due to their long cycle life, lack of geographical limitations, absence of fossil fuel requirements and compatibility with integration into conventional fossil-fuelled power plants. Based on this evidence, in the present study, the dynamic behaviour of an Integrated Thermal Electricity Storage System using Aspen Plus has been investigated. Aspen Plus is a pivotal tool for modelling both steady-state and dynamic systems, enabling the connection of components from its software library through streams. In instances where a specific component is not available in the library, Aspen Modeler can be utilized to model it, and subsequently, it can be integrated into Aspen Plus. This is exemplified in this study, where a packed bed is modelled using Aspen Modeler and incorporated into the overall system analysis

5G SAW-less FDD architecture design

This thesis introduces a new Full-Duplex (FD) architecture for mobile communication standards, eliminating the need for external Surface Acoustic Wave (SAW) filters. It starts with a review of standard requirements, an analysis of overall architecture constraints and presentation of simulation results, this work proposes a two-path noise-cancelling architecture. In this architecture, the main receiver captures the input signal from the antenna, while the auxiliary receiver captures noise leakage from the transmitter. The noise cancellation is performed in the digital domain through an adaptive digital filter. A main receiver topology based on a positive translational feedback loop is chosen for its excellent attributes, including high linearity and low noise. The forward path includes a low-noise transconductance amplifier (LNTA), four phase passive mixers and third-order filtering transimpedance amplifiers. A tunable RC feedback path is loaded at the baseband output, followed by additional four-phase passive up-conversion mixers, enabling tunable, frequency-selective input matching. An analytical model of the structure alongside measurement results will be provided in the dedicated chapter. The auxiliary receiver is designed specifically to increase the ratio between its compression point and its noise figure, with minimal power consumption. The architecture chosen is a LNTA-first with a second-order baseband filter. Thanks to the high input impedance of this receiver it can be placed at the transmitter output without adding considerable loading effects. Measurement results of this auxiliary receiver are presented at the end of the chapter. For the observation of noise cancellation, a Field-Programmable Gate Array (FPGA) is programmed in order to acquire signals from the receivers. The design includes a Clock and Data Recovery (CDR) module, a storage memory and a Universal Asynchronous Receiver-Transmitter (UART) interface for signal transmission to a computer. The design is subsequently validated, demonstrating signal cancellation in MATLAB through the use of an adaptive digital filter employing the Least Mean Squares (LMS) algorithm.This thesis introduces a new Full-Duplex (FD) architecture for mobile communication standards, eliminating the need for external Surface Acoustic Wave (SAW) filters. It starts with a review of standard requirements, an analysis of overall architecture constraints and presentation of simulation results, this work proposes a two-path noise-cancelling architecture. In this architecture, the main receiver captures the input signal from the antenna, while the auxiliary receiver captures noise leakage from the transmitter. The noise cancellation is performed in the digital domain through an adaptive digital filter. A main receiver topology based on a positive translational feedback loop is chosen for its excellent attributes, including high linearity and low noise. The forward path includes a low-noise transconductance amplifier (LNTA), four phase passive mixers and third-order filtering transimpedance amplifiers. A tunable RC feedback path is loaded at the baseband output, followed by additional four-phase passive up-conversion mixers, enabling tunable, frequency-selective input matching. An analytical model of the structure alongside measurement results will be provided in the dedicated chapter. The auxiliary receiver is designed specifically to increase the ratio between its compression point and its noise figure, with minimal power consumption. The architecture chosen is a LNTA-first with a second-order baseband filter. Thanks to the high input impedance of this receiver it can be placed at the transmitter output without adding considerable loading effects. Measurement results of this auxiliary receiver are presented at the end of the chapter. For the observation of noise cancellation, a Field-Programmable Gate Array (FPGA) is programmed in order to acquire signals from the receivers. The design includes a Clock and Data Recovery (CDR) module, a storage memory and a Universal Asynchronous Receiver-Transmitter (UART) interface for signal transmission to a computer. The design is subsequently validated, demonstrating signal cancellation in MATLAB through the use of an adaptive digital filter employing the Least Mean Squares (LMS) algorithm

Understanding change – developing a typology of therapy outcomes from the experience of adolescents with depression

Background: Outcome measures mostly focusing on symptom reduction to measure change cannot indicate whether any personally meaningful change has occurred. There is a need to broaden the current understanding of outcomes for adolescent depression and identify whether holistic, interlinked patterns of change may be more clinically meaningful. Objective: To create a typology of therapy outcomes based on the experiences of adolescents with depression. Method: Interview data from 83 participants from a clinical trial of the psychological treatment of adolescent depression was analysed using ideal type analysis. Results: Six ideal types were constructed, reflecting different evaluations of the holistic impact of therapy: “I’ve worked on my relationships”, “With the insight from therapy, and feeling validated, I can cope with life challenges better”, “My mood still goes up and down”, “If I want things to change, I need to help myself”, “Therapy might help, but it hasn’t been enough”, and “I don’t feel therapy has helped me”. Conclusion: Assessing change using outcome measures may not reflect the interconnected experience for adolescents or the contextual meaning of symptom change. The typology developed offers a way of considering the impact of therapy, taking into account how symptom change is experienced within a broader perspective

Periodistas quemados en una sociedad quemada

El 7 de junio fue el día del periodista en Argentina. Para esa fecha, todos los años desde el Sindicato de Prensa de Buenos Aires (SiPreBA) publicamos un relevamiento sobre la situación económica y social del sector, esta vez sobre una base de más de mil periodistas, aproximadamente un 20% de la actividad. El dato saliente fueron los salarios de pobreza y la precarización laboral. Pero cada vez con más fuerza, particularmente desde la pandemia, cuando nuestra actividad fue declarada esencial y nuestros compañeros y compañeras cubrían noticias en la calle o compartían un estudio de radio, de TV o un control, mientras la mayoría de la población sostenía al aislamiento preventivo, comienzan a aparecer problemas vinculados al padecimiento psíquico y mental. En la encuesta 2024, el 22% de las personas afirmó haber sufrido problemas de salud vinculados al trabajo. Entre los síntomas que mencionan se encuentran la ansiedad, el estrés, la imposibilidad de olvidarse de los problemas laborales, alteraciones del estado de ánimo, tensión, depresión, irritación, alteraciones del sueño y falta de concentración

“I can’t escape my scars, even if I do get better”: A qualitative exploration of how adolescents talk about their self-harm and self-harm scars during cognitive behavioural therapy for depression

Emerging evidence indicates that perceptions of self-harm behaviours and self-harm scars may thwart recovery from depression, yet limited research has explored adolescent accounts of their self-harm and scars during therapy. This study sought to explore how adolescents describe their self-harm behaviours and scars during Cognitive Behavioural Therapy (CBT) and explore the sociocultural discourses that may influence these descriptions. The participants were six female adolescents (aged 14-17 years old) with clinical depression, who were engaging in self-harm. All participants accessed CBT as part of clinical trial evaluating three psychological treatments for major depressive disorder in Child and Adolescent Mental Health Services. Audio-taped CBT sessions were analyzed using discourse analysis. Within CBT sessions, adolescents drew upon stigma discourses in talking about their self-harm. Adolescent also described their self-harm scars as shameful and stigmatizing, and as "proof" of the legitimacy of their depression. It is important for CBT practitioners to understand the context of sociocultural discourses around self-harm behaviours and self-harm scars, which are reflected in how adolescents with depression describe these within therapy and may serve to maintain distress. The study indicates that awareness of use of language and intersecting sociocultural discourses can inform CBT practice