Pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in bipolar disorder: A systematic review.

BACKGROUND: The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic symptomatology of bipolar disorder (BD). Among a broad range of mechanisms implicated, immune dysregulation may contribute to the increased inflammation that influences the course of BD. Inflammatory, neurotrophic and oxidative stress factors may be identified as promising peripheral biomarkers in brain functioning, perhaps serving as predictors of an effective response to treatment for BD. The present systematic review aimed to examine the evidence supporting the pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in BD. METHODS: PubMed, PsychINFO, Scopus and Web of Science were searched from inception to May 2024 by two independent reviewers. A total of 40 studies with 3371 patients with diagnosis and intervention of BD were selected. RESULTS: Inconsistencies in the effects of pharmacological treatments on the connection between the expected anti-inflammatory response and symptomatologic improvement were identified. Mood stabilizers (lithium), antipsychotics (quetiapine), antidepressants (ketamine) or their combination were described to increase both pro-inflammatory (TNFα, IL-6) and anti-inflammatory (IL-4, IL-8) factors. Other medications, such as memantine and dextromethorphan, autoimmune (infliximab) non-steroidal anti-inflammatory (aspirin, celecoxib) drugs, antidiabetics (pioglitazone), and even dietary supplementation (omega-3), or their combination, clearly decrease inflammatory factors (TNFα, IL-6, IL-1ß, C-reactive protein) and/or increase the neurotrophic factor BDNF in BD patients. CONCLUSION: Inflammation in BD requires further investigation to understand the underlying immunologic mechanism, to identify predictors of treatment response, and to make informed decisions about the use and development of more effective pharmacological interventions for BD.

Suicidal behavior in persons attended in out-of-hospital emergency services in Spain.

Background: The aims of this study were to describe the use of health services by patients attended for suicidal behavior by out-of-hospital emergency services and to identify the variables associated with the repetition of this behavior in Spain. Methods: An analytical, observational, retrospective study was carried out. A total of 554 patients attended by the mobile teams of the Primary Care Emergency (mt-PCES) of the Malaga Health District (Spain), after being coordinated by the 061 Emergency Coordination Center (ECC) were analyzed. Results: Of the total, 61.9% of the patients were women and the mean age was 43.5 years. Ninety-six percent (N = 532) of the patients attended by mt-PCES were transferred to hospital emergency services. Regarding clinical decision, of those transferred 436 persons (82%) were discharged home. Of the total sample 25.5% (N = 141) were referred to primary care, while 69% (N = 382) were referred to outpatient mental health care. Regarding follow up in the 6 months after being seen by emergency services, among those referred to a mental health facility, 64.4% (N = 246) attended the follow-up appointment while out of the total sample only 50.5% (N = 280) attended a follow-up appointment with an outpatient mental health service. Finally, it should be noted that 23.3% presented a relapse of suicidal behavior in the 6 months following index episode. The variables associated with repetition of suicidal behavior were older age, greater number of previous suicide attempts and having any contact with mental health services in the following 6 months. Conclusion: We believe that selective suicide prevention initiatives should be designed to target the population at risk of suicide, especially those receiving both out-of-hospital and in-hospital emergency services.

Deep Eutectic Solvents Formed by Glycerol and Xylitol, Fructose and Sorbitol: Effect of the Different Sugars in Their Physicochemical Properties.

The search for new eutectic solvents for different applications (extraction, drug formulation, chemical reactions, etc.) is booming thanks to their high solubility capacity and low toxicity. However, it is necessary to carry out a comprehensive physicochemical characterization of these mixtures to understand the molecular behavior at different experimental conditions. In this study, three deep eutectic solvents (DESs) formed by glycerol and xylitol, fructose and sorbitol and water in the molar ratio 1:2:3 were prepared and several physicochemical properties (refractive index, density, surface tension, viscosity, speed of sound, isobaric heat capacity and isentropic compressibility) were measured and analyzed in the 278.15-338.15 K temperature range. The results indicate a linear dependence with temperature for the following properties: surface tension, refractive index, density and isobaric molar heat capacity while viscosity values have been fitted to the Vogel-Fulcher-Tammann equation.

Deep eutectic solvents based on sugars for oral applications.

Solubility is a critical parameter in drug formulation to achieve the desired therapeutical concentration. Most drugs are weak acids or bases and, therefore, exhibit low solubility and poor oral availability. The main aim of this work is the use of Deep Eutectic Systems (DESs) for improving the solubility of drugs in aqueous medium. In this case, we use DESs formed by choline chloride and sugars (xylitol, fructose, glucose and sorbitol) at different proportions of water. These compounds present low toxicity, and thus can be used in syrups or liquid formulations. Different physicochemical properties, such as density, refractive index, and surface tension, were obtained. In addition, a rheological study of the different systems was carried out. Finally, these DESs were applied to analyse the solubility of the following active principles: caffeine (Class I) and furosemide (Class IV) of the Biopharmaceutics Classification System (BCS). The selection of the drugs attends to different reasons. On one hand, we want to develop a new liquid formulation for model drug furosemide and, on the other hand, the study of caffeine, instead, will be used as a model for comparing purposes. Solubility results show that the systems that best solubilize caffeine are those with the highest water content; however, they do not reach the levels of solubility of pure water. On the other hand, for furosemide, a great increase in solubility was observed, especially for systems formed by xylitol and, fundamentally, in the system with the lowest water content. Obtaining an increase in solubility of up to 4530 times. These systems provide an opportunity to improve the formulation of drugs in the liquid medium of active ingredients that are poorly soluble in an aqueous medium.

The Inflammatory Signals Associated with Psychosis: Impact of Comorbid Drug Abuse.

Psychosis and substance use disorders are two diagnostic categories whose association has been studied for decades. In addition, both psychosis spectrum disorders and drug abuse have recently been linked to multiple pro-inflammatory changes in the central nervous system. We have carried out a narrative review of the literature through a holistic approach. We used PubMed as our search engine. We included in the review all relevant studies looking at pro-inflammatory changes in psychotic disorders and substance use disorders. We found that there are multiple studies that relate various pro-inflammatory lipids and proteins with psychosis and substance use disorders, with an overlap between the two. The main findings involve inflammatory mediators such as cytokines, chemokines, endocannabinoids, eicosanoids, lysophospholipds and/or bacterial products. Many of these findings are present in different phases of psychosis and in substance use disorders such as cannabis, cocaine, methamphetamines, alcohol and nicotine. Psychosis and substance use disorders may have a common origin in an abnormal neurodevelopment caused, among other factors, by a neuroinflammatory process. A possible convergent pathway is that which interrelates the transcriptional factors NFκB and PPARγ. This may have future clinical implications.

Surface Tensions of Alkyl Lactates with n-Alkanols or Branched Alkanols.

The surface behavior of 18 binary mixtures at T = 298.15 K and at atmospheric pressure (p = 0.1 MPa) was measured with a drop volume tensiometer. These mixtures are formed by alkyl lactates (methyl lactate and ethyl lactate) and alcohols (n-alkanols from methanol to 1-hexanol and isomeric butanols). Surface tension deviations for all these systems were calculated and correlated with the mole fraction using the Myers-Scott equation. For the mixtures alkyl lactate with methanol, the surface tension deviations are positive. With regard to the mixtures containing ethanol, the surface tension deviation is positive for methyl lactate and slightly negative in the lactate-poor region for ethyl lactate. For the rest of the mixtures, the surface tension deviations are negative. A molecular interpretation of the different behaviors observed was proposed.

Aripiprazole for the treatment of schizophrenia: Recommendations of a panel of Spanish experts on its use in clinical practice.

OBJECTIVES: Aripiprazole is an antipsychotic with a partial agonism of dopamine D2 and D3 receptors. This differential mechanism implies a rigorous appraisal of the appropriate therapeutic strategies in certain situations. To answer currently unsolved clinical questions about the use of oral and long-acting injectable (LAI) aripiprazole, we present here an expert consensus from 12 Spanish psychiatrists and a pharmacologist with extensive experience in the use of this antipsychotic. METHODS: Through one face-to-face session and online collaboration, we reached consensus and established practical recommendations based on scientific evidence and clinical experience. We classified the available scientific literature according to SIGN system and attributed a level of evidence to each reviewed article. RESULTS: The recommendations were divided according to (i) chronological dimension (based on previous treatments, including patients naïve or not to antipsychotic treatment and maintenance regimen), and (ii) dimension related to therapeutic options, comprising switches to aripiprazole and the most used combinations with this antipsychotic. CONCLUSIONS: We recommend considering aripiprazole as first treatment option in the early stages of schizophrenia and in patients with affective symptoms and contemplating a switch to aripiprazole LAI in all candidate patients. Importantly, switches from other antipsychotics should consider previous antipsychotic history and exposure to aripiprazole. KEYPOINTSAripiprazole can be considered as first treatment option in early stages of schizophrenia and in patients with significant affective symptoms.Aripiprazole LAI shows better adherence than oral aripiprazole and could be considered in all candidate patients.Before switching to aripiprazole, detailed information about previous antipsychotic history should be gathered.Switch to aripiprazole should be managed differently for aripiprazole naïve and non-naïve patients.Rigorous and controlled studies on antipsychotics in real clinical practice should be carried out.

Clinical Value of Inflammatory and Neurotrophic Biomarkers in Bipolar Disorder: A Systematic Review and Meta-Analysis.

Bipolar disorder (BD) is a multifactorial chronic psychiatric disease highly defined by genetic, clinical, environmental and social risk factors. The present systematic review and meta-analysis aimed to examine the relationship between inflammatory and neurotrophic factors and clinical, social and environmental factors involved in the development and the characterization of BD. Web of Science, PubMed, PsycINFO, Scopus and Science Direct were searched by two independent reviewers. The systematic review was registered in PROSPERO (CRD42020180626). A total of 51 studies with 4547 patients with a diagnosis of BD were selected for systematic review. Among them, 18 articles were included for meta-analysis. The study found some evidence of associations between BDNF and/or inflammatory factors and different stressors and functional and cognitive impairment, but limitations prevented firm conclusions. The main finding of the meta-analysis was a negative correlation between circulating levels of BDNF and depression severity score (standardized mean difference = -0.22, Confidence Interval 95% = -0.38, -0.05, p = 0.01). Evidence indicates that BDNF has a role in the depressive component of BD. However, the poor consistency found for other inflammatory mediators clearly indicates that highly controlled studies are needed to identity precise biomarkers of this disorder.

Trends in Psychiatric Hospitalizations of Patients With Dual Diagnosis in Spain.

OBJECTIVE: Substance use disorders are highly prevalent in people living with a mental health disorder. Co-occurring substance use disorders have been associated with a worse prognosis and poorer adherence to treatment. The aim of this study was to analyze the temporal trends in the prevalence of substance use disorders in patients admitted to a psychiatric inpatient unit between 1998 and 2020. METHODS: This is a retrospective study based on the registry of 18,367 hospitalizations and 7,124 patients with a mental health disorder admitted during the period 1998 to 2020 in Malaga, Spain. Time trend analysis by gender and substance used was calculated using a segmented regression model. The permutation test was used to determine inflection points. A sensitivity analysis was performed based on the assumptions of autocorrelation and homoscedasticity. RESULTS: A total of 22.2% of admissions had a diagnosis of mental health disorder and co-occurring substance use disorders. Prevalence was higher among males (30.0%) than females (9.4%; p < .001). Patients with both disorders had a shorter length of stay by 2 days (p < .001) and a younger age at first admission (by 6.5 years; p < .001) compared to patients without substance use disorders. There was no difference in the total number of hospitalizations between the two groups. Psychotic disorders and multiple drug use disorders were the most prevalent diagnoses in men compared to women, whereas personality disorders and alcohol use were the most common diagnoses in women. We observed an increase in the prevalence of dual diagnosis between 2005 and 2020. There was a 3.0% increase in cannabis-related admissions per year during the whole study period (p < .001). Cannabis and cocaine use disorders have become the most prevalent in the last 10 years, while opioid and alcohol use disorders have decreased. CONCLUSIONS: Co-occurring substance use disorders are highly prevalent among hospitalized patients. In recent years, the pattern of substance use has shifted, with cannabis being the most prevalent, while opiates and alcohol substance use have decreased. We need to devise a specialized approach and integrative treatment for patients with co-occurring disorders.

The Impact of COVID-19 Confinement on Cognition and Mental Health and Technology Use Among Socially Vulnerable Older People: Retrospective Cohort Study.

BACKGROUND: COVID-19 forced the implementation of restrictive measures in Spain, such as lockdown, home confinement, social distancing, and isolation. It is necessary to study whether limited access to basic services and decreased family and social support could have deleterious effects on cognition, quality of life, and mental health in vulnerable older people. OBJECTIVE: This study aims to explore the impact of the COVID-19 outbreak on cognition in older adults with mild cognitive impairment or dementia as the main outcome and the quality of life, perceived health status, and depression as secondary outcomes and to analyze the association of living alone and a change in living arrangements with those outcomes and other variables related with the use of technology and health services. Likewise, this study aims to analyze the association of high and low technophilia with those variables, to explore the access and use of health care and social support services, and, finally, to explore the informative-, cognitive-, entertainment-, and socialization-related uses of information and communications technologies (ICTs) during the COVID-19 outbreak. METHODS: This cohort study was conducted in Málaga (Spain). In total, 151 participants with mild cognitive impairment or mild dementia, from the SMART4MD (n=75, 49.7%) and TV-AssistDem (n=76, 50.3%) randomized clinical trials, were interviewed by telephone between May 11 and June 26, 2020. All participants had undergone 1-3 assessments (in 6-month intervals) on cognition, quality of life, and mood prior to the COVID-19 breakout. RESULTS: The outbreak did not significantly impact the cognition, quality of life, and mood of our study population when making comparisons with baseline assessments prior to the outbreak. Perceived stress was reported as moderate during the outbreak. After correction for multiple comparisons, living alone, a change in living arrangements, and technophilia were not associated with negative mental health outcomes. However, being alone was nominally associated with self-perceived fear and depression, and higher technophilia with better quality of life, less boredom, perceived stress and depression, and also less calmness. Overall, health care and social support service access and utilization were high. The most used ICTs during the COVID-19 outbreak were the television for informative, cognitive, and entertainment-related uses and the smartphone for socialization. CONCLUSIONS: Our findings show that the first months of the outbreak did not significantly impact the cognition, quality of life, perceived health status, and depression of our study population when making comparisons with baseline assessments prior to the outbreak. Living alone and low technophilia require further research to establish whether they are risk factors of mental health problems during lockdowns in vulnerable populations. Moreover, although ICTs have proven to be useful for informative-, cognitive-, entertainment-, and socialization-related uses during the pandemic, more evidence is needed to support these interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04385797; https://clinicaltrials.gov/ct2/show/NCT04385797. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/26431.

Thermophysical Study of Pyridinium-Based Ionic Liquids Sharing Ions.

The thermophysical properties of three pyridinium-based ionic liquids sharing ions were measured at several temperatures (278.15-338.15) K and at atmospheric pressure (0.1 MPa). Three ionic liquids were studied: 1-butylpyridinium bis(trifluoromethyl-sulfonyl)imide, 1-hexylpyridinium bis(trifluoromethylsulfonyl)imide, and 1-hexylpyridinium tetrafluoroborate. The following thermophysical properties were measured: density, speed of sound, refractive index, surface tension, isobaric molar heat capacity, kinematic viscosity, and electrical conductivity. The thermophysical properties at atmospheric pressure were correlated with temperature, noting that the starting temperature for the speed of sound measurements depended on the ionic liquid. From these experimental results, some derived properties (isentropic compressibility, molar refraction, and dynamic viscosity) are calculated. These results together with those published previously for 1-butylpyridinium tetrafluoroborate are discussed.

Migration of Medical Professionals: The Case of Psychiatric Trainees in Spain.

The social and economic situation in Europe seems to play a role in the migratory flow of doctors and other health professionals within the continent. However, little is known about the particular reality of workforce migration in Spain. The objective of this study was to explore the factors that motivate migration among junior doctors training in psychiatry in Spain. A semistructured questionnaire of 61 items was circulated to psychiatric trainees in Spain to explore the extent and the factors that influence the decisions regarding workforce migration. A total of 95 psychiatric trainees participated in the survey. More than two-thirds (n = 71, 74.7%) had "ever" considered migrating to another country, and more than one-fourth (n = 21, 29.5%) had already taken "practical steps" to go abroad. The main reasons to consider leaving the country were financial (n = 82, 86%) and the opportunity to progress professionally (n = 82, 84%). However, nearly half of the trainees (n = 47, 49%) were satisfied with their current income. While the majority of the psychiatric trainees in this survey had considered migrating abroad, these potential future migrations could lead to a loss of human capital with an important sociosanitary impact.

Met and Unmet Needs in an Inpatient Psychiatry Setting in Spain.

PURPOSE: Patients with severe mental disorder have health and social needs that require care. The aim of the study was to determine the main areas of perceived needs among inpatients with severe mental disorders and to identify risk factors of the group of patients with the greatest unmet needs. PATIENTS AND METHODS: A total of 150 patients with severe mental illness were assessed during admission prior to discharge from the hospital. Camberwell Assessment of Needs was used as evaluation measure, in addition to clinical status (The Brief Psychiatric Rating Scale), social functioning (Personal and Social Performance) and sociodemographic variables. A descriptive and a multivariate logistic regression analysis were used to analyse variables related to the group of patients with the highest number of unmet needs (≥3). RESULTS: Mean number of needs was 7.93, being 4.61 the mean number of needs met and 3.32 the needs unmet. The highest proportion of unmet needs were intimate relationships (44.0%), company (40.7%) and daytime activities (38.7%). A relationship was also found between the presence of three or more unmet needs and the following variables: Brief Psychiatric Rating Scale score (p=0.004), Personal and Social Performance score (p = 0.013), marital status (p=0.018), employment status (p=0.009) and voluntary admission (p=0.032). The multivariate model explained 29.5% of the variance (Nagelkerke's R2: 0.295). CONCLUSION: Treatments aimed at improving social relationships and daytime activities could be a good option for inpatients with many unmet needs.

Ecotoxicity and biodegradability of pure and aqueous mixtures of deep eutectic solvents: glyceline, ethaline, and reline.

Most of the works carried out on deep eutectic solvents (DESs) make reference to their physicochemical properties, and the analysis of their toxicological behavior on the environment and biodegradability are still limited. In this work, an exhaustive study on the ecotoxicity of three pure deep eutectic solvents (reline, glyceline, and ethaline) and their mixtures with water (reline-water, glyceline-water, and ethaline-water) was carried out in different biomodels: bacteria (A. fisheri), crustaceans (D. magna), and algae (S. capricornatum). In addition, the amount of chlorophyll in the algae after exposure to the DESs was analyzed. Finally, the biodegradability of the studied DESs was also analyzed. The ecotoxic behavior strongly depends on both the biomodel tested and the presence of water in the mixture, resulting in low toxicities in all cases. Furthermore, most of the deep eutectic solvents studied can be considered readily biodegradable. A comparison of the ecotoxicity and biodegradability of these solvents under other conditions has also been provided, and a complete analysis is given.

Structure and properties of two glucose-based deep eutectic systems.

Continued industrialization and increasing environmental problems have highlighted the need to research new eco-friendly solvents, also known as deep eutectic solvents (DESs). To implement these solvents in industrial processes, the knowledge of their molecular organization and thermophysical properties must be enhanced. In this work, two DESs have been characterized: d-glucose:choline chloride:water (GCH) and d-glucose:citric acid:water (GCiH). NMR techniques were used to analyse both the supramolecular structure and the role of water and to calculate the diffusion coefficients. Moreover, seven thermophysical properties at several temperatures were evaluated. As a second aim, the solubility of quercetin was determined. NMR studies showed a stronger supramolecular structure of GCH and a high ratio of ß-glucose in both DESs. Based on the thermophysical results, the solvent with choline chloride had the most compact fluid structure. Finally, the solubility of quercetin in the DESs was higher than in water, especially for GCH.

QSAR study for predicting the ecotoxicity of NADES towards Aliivibrio fischeri. Exploring the use of mixing rules.

(Eco)toxicological information of natural deep eutectic solvents (NADES) is scarce, and thus, quantitative structure activity relationship (QSAR) models are an important tool for achieving the prediction of toxicity in this case. For that reason, in this manuscript, a new QSAR model for predicting the ecotoxicity of NADES towards the Aliivibrio fischeri biomodel, using mixing rules, is proposed. The main advantage of the method is that the individual components of the mixtures are molecularly modelled, and then, a mixing rule is used, which simplifies the process. For developing the model, a total of 11 descriptors for each component is used: the dissociation constant, partition coefficient, Van der Waals volume, Van der Waals surface area, topological polar surface area, solvent accessible surface area, minimum projection area, maximum projection area, minimum projection radius, maximum projection radius and molecular weight. The final obtained model includes the topological polar surface area and the dissociation constant, mechanistically interpreted as the ability of a NADES to transport through biological membranes and the severe negative effect of pH on the toxicity and biological response of Aliivibrio fischeri bacteria. The OECD Guidance Document on the Validation of (Quantitative) Structure-Activity Relationships is followed to develop the mathematical model.

Characterization of xylitol or citric acid:choline chloride:water mixtures: Structure, thermophysical properties, and quercetin solubility.

The industrial implementation of new eco-friendly solvents has highlighted the need to analyse both the structures and thermophysical properties of these solvents. Here, two deep eutectic solvents (DESs) used in the agro-food field were studied: xylitol:choline chloride:water (1:2:3 M ratio), XoCH, and citric acid:choline chloride:water (1:1:6 M ratio), CiCH. The H-bond network between the components of each DES was evaluated and the diffusion coefficients at 298.15 K were calculated using NMR spectroscopy. In addition, seven thermophysical properties were determined from 278.15 to 338.15 K. Also, the solubility of quercetin in water and in the two eutectic mixtures was measured and the interactions between components were studied. NMR experiments revealed the presence of water within the supramolecular structure of XoCH, but CiCH is a "DES-in-water" solution. Based on the results, XoCH is the most compact mixture. Finally, quercetin was remarkably more soluble in the studied DESs than in pure water.

Toward Improving Early Diagnosis of Congenital Chagas Disease in an Endemic Setting.

BACKGROUND: Congenital Trypanosoma cruzi transmission is now estimated to account for 22% of new infections, representing a significant public health problem across Latin America and internationally. Treatment during infancy is highly efficacious and well tolerated, but current assays for early detection fail to detect >50% of infected neonates, and 9-month follow-up is low. METHODS: Women who presented for delivery at 2 urban hospitals in Santa Cruz Department, Bolivia, were screened by rapid test. Specimens from infants of infected women were tested by microscopy (micromethod), quantitative PCR (qPCR), and immunoglobulin (Ig)M trypomastigote excreted-secreted antigen (TESA)-blots at birth and 1 month and by IgG serology at 6 and 9 months. RESULTS: Among 487 infants of 476 seropositive women, congenital T. cruzi infection was detected in 38 infants of 35 mothers (7.8%). In cord blood, qPCR, TESA-blot, and micromethod sensitivities/specificities were 68.6%/99.1%, 58.3%/99.1%, and 16.7%/100%, respectively. When birth and 1-month results were combined, cumulative sensitivities reached 84.2%, 73.7%, and 34.2%, respectively. Low birthweight and/or respiratory distress were reported in 11 (29%) infected infants. Infants with clinical signs had higher parasite loads and were significantly more likely to be detected by micromethod. CONCLUSIONS: The proportion of T. cruzi-infected infants with clinical signs has fallen since the 1990s, but symptomatic congenital Chagas disease still represents a significant, albeit challenging to detect, public health problem. Molecular methods could facilitate earlier diagnosis and circumvent loss to follow-up but remain logistically and economically prohibitive for routine screening in resource-limited settings.

SERP: una Sociedad en crecimiento y con horizonte europeo / SERP: a growing society and with an European horizon

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