Dysregulation of Plasma Growth Factors and Chemokines in Cocaine Use Disorder: Implications for Dual Diagnosis with Schizophrenia and Antisocial Personality Disorder in an Exploratory Study.

INTRODUCTION: Dual diagnosis in individuals with cocaine use disorders (CUDs) presents a mental health challenge marked by an increased susceptibility to disabling morbidities and premature mortality. Despite extensive research on depression and anxiety, other prevalent comorbidities, such as psychotic and personality disorders, have received less attention. This study explores inflammation-related mediators as potential biomarkers for CUD and dual diagnosis with schizophrenia (SCZ) or antisocial personality disorder (APD). METHODS: This exploratory study included 95 participants, comprising 40 healthy subjects and 55 abstinent patients with CUD. Lifetime CUD was diagnosed either as single diagnosis (CUD group, N = 25) or as a dual diagnosis (DD group. N = 30) with SCZ (CUD+SCZ subgroup) or APD (CUD+APD subgroup). Participants were clinically assessed, and the plasma concentrations of growth factors (i.e., G-CSF, BDNF, and VEGF-A) and chemokines (i.e., CCL11/eotaxin-1, CCL2/MCP-1, and CXCL12/SDF-1) were determined and log(10)-transformed for analysis. RESULTS: Growth factors and chemokines were dysregulated by CUD and psychiatric diagnoses. Specifically, patients in the CUD group exhibited significantly lower concentrations of G-CSF and CCL11/eotaxin-1 than the control group. In contrast, the DD group showed significantly higher concentrations of all analytes than both the CUD and control groups. Additionally, no differences in these analytes were observed between the CUD+SCZ and CUD+APD subgroups within the DD group. Regarding cocaine-related variables, significant associations were identified in the CUD group: an inverse correlation between the age at first cocaine use and the concentrations of BDNF and CCL2/MCP-1; and a positive correlation between the duration of the cocaine abstinence and the concentrations of BDNF and CCL11/eotaxin-1. Lastly, a logistic regression model incorporating all these analytes demonstrated high discriminatory power in distinguishing patients with CUD alone from those with dual diagnosis. CONCLUSIONS: Individuals with dual diagnosis of CUD exhibit elevated concentrations of growth factors and chemokines, distinguishing them from those with CUD alone. It is unclear whether the differences in these inflammatory mediators are specific to the presence of SCZ and APD. The study highlights potential biomarkers and associations, providing valuable insights into the intricate interplay of CUD and psychiatric disorders to enhance clinical diagnosis and therapeutics.

Plants from Arid and Semi-Arid Zones of Mexico Used to Treat Respiratory Diseases: A Review.

Medicinal plants have been a traditional remedy for numerous ailments for centuries. However, their usage is limited due to a lack of evidence-based studies elucidating their mechanisms of action. In some countries, they are still considered the first treatment due to their low cost, accessibility, and minor adverse effects. Mexico is in second place, after China, in inventoried plants for medicinal use. It has around 4000 species of medicinal plants; however, pharmacological studies have only been carried out in 5% of its entirety. The species of the Mexican arid zones, particularly in semi-desert areas, exhibit outstanding characteristics, as their adverse growing conditions (e.g., low rainfall and high temperatures) prompt these plants to produce interesting metabolites with diverse biological activities. This review explores medicinal plants belonging to the arid and semi-arid zones of Mexico, focusing on those that have stood out for their bioactive potential, such as Jatropha dioica, Turnera diffusa, Larrea tridentata, Opuntia ficus-indica, Flourensia cernua, Fouquieria splendes, and Prosopis glandulosa. Their extraction conditions, bioactive compounds, mechanisms of action, and biological efficacy are presented, with emphasis on their role in the treatment of respiratory diseases. Additionally, current research, novel applications, and perspectives concerning medicinal plants from these zones are also discussed.

Plasma Concentrations of High Mobility Group Box 1 Proteins and Soluble Receptors for Advanced Glycation End-Products Are Relevant Biomarkers of Cognitive Impairment in Alcohol Use Disorder: A Pilot Study.

Alcohol use disorder (AUD) is a major component in the etiology of cognitive decline and dementia. Underlying mechanisms by which long-term alcohol abuse causes cognitive dysfunction include excessive oxidative stress and inflammation in the brain, activated by increased reactive oxygen/nitrogen species (ROS/RNS), advanced glycation end-products (AGEs) and high-mobility group box 1 protein (HMGB1). In a pilot study, we examine the potential clinical value of circulating biomarkers of oxidative stress including ROS/RNS, HMGB1, the soluble receptor for AGE (sRAGE), the brain biomarker of aging apolipoprotein D (ApoD), and the antioxidant regulator nuclear factor erythroid 2-related factor 2 (NRF2) as predictive indices for cognitive impairment (CI) in abstinent patients with AUD (n = 25) compared to patients with established Alzheimer's disease (AD, n = 26) and control subjects (n = 25). Plasma concentrations of sRAGE were evaluated with immunoblotting; ROS/RNS with a fluorometric kit; and HMGB1, ApoD, and NRF2 by ELISA. Abstinent AUD patients had higher sRAGE, ROS/RNS (p < 0.05), and ApoD (p < 0.01) concentrations, similar to those of AD patients, and lower NRF2 (p < 0.01) concentrations, compared to controls. These changes were remarkable in AUD patients with CI. HMGB1, and sRAGE correlated positively with duration of alcohol use (rho = 0.398, p = 0.022; rho = 0.404, p = 0.018), whereas sRAGE correlated negatively with periods of alcohol abstinence (rho = -0.340, p = 0.045). A predictive model including ROS/RNS, HMGB1, sRAGE, alcohol use duration, and alcohol abstinence periods was able to differentiate AUD patients with CI (92.3% of correct predictions, ROC-AUC= 0.90) from those without CI. In conclusion, we propose ROS/RNS, HMGB1, and sRAGE as stress biomarkers capable of predicting cognitive impairment in AUD patients.

Plasma Lysophosphatidic Acid Concentrations in Sex Differences and Psychiatric Comorbidity in Patients with Cocaine Use Disorder.

We have recently reported sex differences in the plasma concentrations of lysophosphatidic acid (LPA) and alterations in LPA species in patients with alcohol and cocaine use disorders. Preclinical evidence suggests a main role of lysophosphatidic acid (LPA) signaling in anxiogenic responses and drug addiction. To further explore the potential role of the LPA signaling system in sex differences and psychiatric comorbidity in cocaine use disorder (CUD), we conducted a cross-sectional study with 88 patients diagnosed with CUD in outpatient treatment and 60 healthy controls. Plasma concentrations of total LPA and LPA species (16:0, 18:0, 18:1, 18:2 and 20:4) were quantified and correlated with cortisol and tryptophan metabolites [tryptophan (TRP), serotonin (5-HT), kynurenine (KYN), quinolinic acid (QUIN) and kynurenic acid (KYNA)]. We found sexual dimorphism for the total LPA and most LPA species in the control and CUD groups. The total LPA and LPA species were not altered in CUD patients compared to the controls. There was a significant correlation between 18:2 LPA and age at CUD diagnosis (years) in the total sample, but total LPA, 16:0 LPA and 18:2 LPA correlated with age at onset of CUD in male patients. Women with CUD had more comorbid anxiety and eating disorders, whereas men had more cannabis use disorders. Total LPA, 18:0 LPA and 20:4 LPA were significantly decreased in CUD patients with anxiety disorders. Both 20:4 LPA and total LPA were significantly higher in women without anxiety disorders compared to men with and without anxiety disorders. Total LPA and 16:0 LPA were significantly decreased in CUD patients with childhood ADHD. Both 18:1 LPA and 20:4 LPA were significantly augmented in CUD patients with personality disorders. KYNA significantly correlated with total LPA, 16:0 LPA and 18:2 LPA species, while TRP correlated with the 18:1 LPA species. Our results demonstrate that LPA signaling is affected by sex and psychiatric comorbidity in CUD patients, playing an essential role in mediating their anxiety symptoms.

Mechanisms and Applications of Citral's Antimicrobial Properties in Food Preservation and Pharmaceuticals Formulations.

Citral is a monoterpene constituted by two isomers known as neral and geranial. It is present in different plant sources and recognized as safe (GRAS) by the Food and Drug Administration (FDA). In recent years, investigations have demonstrated that this compound exhibited several biological activities, such as antibacterial, antifungal, antibiofilm, antiparasitic, antiproliferative, anti-inflammatory, and antioxidant properties, by in vitro and in vivo assays. Additionally, when incorporated into different food matrices, citral can reduce the microbial load of pathogenic microorganisms and extend the shelf life. This compound has acceptable drug-likeness properties and does not present any violations of Lipinski's rules, which could be used for drug development. The above shows that citral could be a compound of interest for developing food additives to extend the shelf life of animal and vegetable origin foods and develop pharmaceutical products.

Antidepressant Medication Does Not Contribute to the Elevated Circulating Concentrations of Acylethanolamides Found in Substance Use Disorder Patients.

Circulating acylethanolamides (NAEs) are bioactive signaling molecules that modulate multiple homeostatic functions including mood and hedonic responses. Variations in their plasma concentrations are associated with substance use disorders (SUD) and recent studies suggest that psychotropic medication might influence its circulating levels, limiting its use as a clinical biomarker of addiction. In addition, they might have a role as mediators of the pharmacological effects of psychotropic drugs. Thus, in mild depression, the response to selective serotonin reuptake inhibitor-type antidepressants (SSRI) is associated with a marked increase in circulating NAEs. To further investigate if antidepressants are able to modify the plasma concentration of NAEs in SUD patients, we analyzed the circulating levels of NAEs in 333 abstinent and 175 healthy controls on the basis of the treatment with SSRI antidepressants. As described previously, SUD patients display higher concentrations of NAEs than those measured in a control population. This increase was not further modified by antidepressant therapy. Only marginal increases in palmitoylethanolamide (PEA), oleoylethanolamide (OEA), or docosatetraenoyl-ethanolamide (DEA) were found, and the net effect was very small. Thus, our study shows that treatment with SSRI-type antidepressants does not modify the clinical utility of monitoring enhanced NAE production as biomarkers of SUD. In addition, the possibility that a blunted NAE response to antidepressant therapy might be related to the loss of efficacy of SSRIs in dual depression emerges as an attractive hypothesis that needs to be addressed in future studies.

Plasma concentrations of lysophosphatidic acid and the expression of its receptors in peripheral blood mononuclear cells are altered in patients with cocaine use disorders.

We have recently reported alterations in the plasma concentrations of lysophosphatidic acid (LPA) in patients with substance use disorders. In order to further explore the potential role of the LPA signaling system as biomarker in cocaine use disorders (CUD) we conducted a cross-sectional study with 105 patients diagnosed with CUD and 92 healthy controls. Participants were clinically evaluated and blood samples were collected to determine plasma concentrations of total LPA and LPA species (16:0-, 18:0-, 18:1-, 18:2-, and 20:4-LPA), and the gene expression of LPA1 and LPA2 receptors in peripheral blood mononuclear cells. We found that patients with CUD had significantly lower plasma concentration of the majority of LPA species, while the mRNA expression of LPA1 receptor was found to be higher than controls. Moreover, we found a positive association between plasma concentration of 20:4-LPA and relevant CUD-related variables: age of onset cocaine use and length of cocaine abstinence. The statistical analysis revealed sex differences in concentrations of total LPA and LPA species, and women showed higher LPA concentrations than men. Furthermore, studies in rats of both sexes showed that plasma concentrations of total LPA were also altered after acute and chronic cocaine administration, revealing a sexual dimorphism in these effects. This study found alterations on the LPA signaling system in both, patients with CUD and rats treated with cocaine. Our results demonstrate that LPA signaling is impacted by CUD and sex, which must be taken into consideration in future studies evaluating LPA as a reliable biomarker for CUD.

Antipsychotic Medication Influences the Discriminative Value of Acylethanolamides as Biomarkers of Substance Use Disorder.

Plasma acylethanolamides (NAEs), including the endocannabinoid anandamide (AEA), have been proposed as circulating biomarkers of substance use disorders. However, the concentration of these lipid transmitters might be influenced by the use of drugs prescribed for either the treatment of addiction or the associated psychiatric co-morbidities such as psychosis. As an example, neuroleptics, used for attenuation of psychotic symptoms and sedation, might theoretically interfere with the monoamine-mediated production of NAEs, obstructing the interpretation of plasma NAEs as clinical biomarkers. To solve the lack of information on the impact of neuroleptics on the concentration of NAEs, we evaluated the concentrations of NAEs in a control group and compared them to those present in (a) substance use disorders (SUD) patients that are not prescribed with neuroleptics, and (b) SUD patients (both alcohol use disorder and cocaine use disorder patients) using neuroleptics. The results demonstrate that SUD patients exhibited greater concentrations of NAEs than the control population, affecting all species with the exception of stearoylethanolamide (SEA) and palmitoleoylethanolamide (POEA). Neuroleptic treatment enhanced the concentrations of NAEs, especially those of AEA, linoleoylethanolamide (LEA), and oleoylethanolamide (OEA). This effect of neuroleptic treatment was observed independently of the drug addiction that motivated the demand for treatment (either alcohol or cocaine). This study remarks the need to control the current use of psychotropic medication as a potential confounding variable when considering the use of NAEs as biomarkers in SUD.

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.

Migración de catéter distal a nivel del recto como complicación de derivación ventriculoperitoneal. Reporte de caso / Catheter Migration Through the Rectum as Ventricular Peritoneal Shunt Complication. Case Report

Resumen La hidrocefalia es una entidad nosológica común que en muchos casos tiene como tratamiento de elección la derivación ventricular hacia cualquier cavidad. Dentro de las complicaciones más frecuentes, tenemos las abdominales con formación de colecciones, así como irrupción a sistema intestinal con posterior migración del mismo con presentación de sintomatología a este nivel. Presentamos el caso de un paciente con nula sintomatología abdominal y migración del catéter distal hacia el recto.

Abstract Hydrocephalus is a common nosological entity, with ventricular shunting towards any cavity as the treatment of choice in many cases. Among the most frequent complications, we have the abdominal ones with the formation of collections, as well as irruption to the intestinal system with subsequent migration of the same with presentation of symptoms at this level. We present the case of a patient with no abdominal symptoms and migration of the distal catheter towards the rectum.

Plasma Concentrations of Neurofilament Light Chain Protein and Brain-Derived Neurotrophic Factor as Consistent Biomarkers of Cognitive Impairment in Alcohol Use Disorder.

For a long time, Substance Use Disorders (SUDs) were not considered a component in the etiology of dementia. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders introduced substance-induced neurocognitive disorders, incorporating this notion to clinical practice. However, detection and monitoring of neurodegenerative processes in SUD patients remain a major clinical challenge, especially when early diagnosis is required. In the present study, we aimed to investigate new potential biomarkers of neurodegeneration that could predict cognitive impairment in SUD patients: the circulating concentrations of Neurofilament Light chain protein (NfL) and Brain-Derived Neurotrophic Factor (BDNF). Sixty SUD patients were compared with twenty-seven dementia patients and forty healthy controls. SUD patients were recruited and assessed using the Psychiatric Research Interview for Substance and Mental (PRISM) and a battery of neuropsychological tests, including the Montreal Cognitive Assessment test for evaluation of cognitive impairment. When compared to healthy control subjects, SUD patients showed increases in plasma NfL concentrations and NfL/BDNF ratio, as well as reduced plasma BDNF levels. These changes were remarkable in SUD patients with moderate-severe cognitive impairment, being comparable to those observed in dementia patients. NfL concentrations correlated with executive function and memory cognition in SUD patients. The parameters "age", "NfL/BDNF ratio", "first time alcohol use", "age of onset of alcohol use disorder", and "length of alcohol use disorder diagnosis" were able to stratify our SUD sample into patients with cognitive impairment from those without cognitive dysfunction with great specificity and sensibility. In conclusion, we propose the combined use of NfL and BDNF (NfL/BDNF ratio) to monitor substance-induced neurocognitive disorder.

Postharvest Quality Improvement of Tomato (Solanum lycopersicum L.) Fruit Using a Nanomultilayer Coating Containing Aloe vera.

The effectiveness of an alginate/chitosan nanomultilayer coating without (NM) and with Aloe vera liquid fraction (NM+Av) was evaluated on the postharvest quality of tomato fruit at 20 °C and 85% relative humidity (RH) to simulate direct consumption. Both nanomultilayer coatings had comparable effects on firmness and pH values. However, the NM+Av coating significantly reduced weight loss (4.5 ± 0.2%) and molds and yeasts (3.5-4.0 log CFU g-1) compared to uncoated fruit (16.2 ± 1.2% and 8.0 ± 0.0 log CFU g-1, respectively). It notably lowered O2 consumption by 70% and a 52% decrease in CO2 production, inhibiting ethylene synthesis. Visual evaluation confirmed NM+Av's efficacy in preserving the postharvest quality of tomato. The preservation of color, indicated by the Minolta color (a*/b*) values, demonstrated NM+Av's ability to keep the light red stage compared to uncoated fruit. The favorable effects of NM+Av coating on enhancing postharvest quality indicates it as a potential alternative for large-scale tomato fruit preservation.

Sex Differences in Plasma Lysophosphatidic Acid Species in Patients with Alcohol and Cocaine Use Disorders.

Preclinical evidence suggests a main role of lysophosphatidic acid (LPA) signaling in drug addiction. Recently, we reported alterations in the plasma concentrations of LPA species in patients with alcohol use disorder (AUD). As there are sex differences in drug addiction, the main aim of the present study was to investigate whether relevant LPA species (16:0-LPA, 18:0-LPA, 18:1-LPA, 18:2-LPA and 20:4-LPA) were associated with sex and/or substance use disorder (SUD). This exploratory study was conducted in 214 abstinent patients with lifetime SUD, and 91 healthy control subjects. The SUD group was divided according to the diagnosis of AUD and/or cocaine use disorder (CUD). Participants were clinically assessed, and plasma samples were collected to determine LPA species and total LPA. We found that LPA concentrations were significantly affected by sex, and women showed higher concentrations than men. In addition, there were significantly lower 16:0-LPA, 18:2-LPA and total LPA concentrations in patients with SUD than in controls. Namely, patients with CUD and AUD + CUD showed lower LPA concentrations than controls or patients with AUD. In conclusion, our data suggest that LPA species could be potential biomarkers for SUD in women and men, which could contribute to a better stratification of these patients in treatment programs.

Vascular Endothelial Growth Factor as a Potential Biomarker of Neuroinflammation and Frontal Cognitive Impairment in Patients with Alcohol Use Disorder.

(1) Background: Alcohol Use Disorder (AUD) is associated with functional disruption of several brain structures that may trigger cognitive dysfunction. One of the mechanisms of alcohol-associated cognitive impairment has been proposed to arise from its direct impact on the immune system, which culminates in the release of cytokines and chemokines which can eventually reach the brain. Alcohol can also disrupt the blood-brain barrier, facilitating the penetration of pro-inflammatory molecules throughout vascular endothelial growth factor A (VEGFA). Thus, alcohol-induced alterations in chemokines and VEGFA might contribute to the neuroinflammation and cognitive impairment associated with AUD. (2) Methods: The present cross-sectional study investigates whether patients with AUD (n = 86) present cognitive disability associated to alterations in plasma concentration of SDF-1, fractalkine, eotaxin, MCP-1, MIP-1α and VEGFA when compared to control subjects (n = 51). (3) Results: The analysis indicated that SDF-1 and MCP-1 concentrations were higher in AUD patients than in controls. Concentrations of VEGFA were higher in AUD patients with severe frontal deficits, and the score of frontal lobe functions was negatively correlated with VEGFA and fractalkine. Acute alcohol effects on VEGFA plasma levels in healthy volunteers demonstrated the induction of VEGFA release by heavy alcohol drinking. VEGFA was positively correlated with pro-inflammatory chemokines in AUD patients with frontal cognitive impairment. (4) Conclusions: we propose VEGFA/chemokine monitoring as biomarkers of potential cognitive impairment in AUD patients.

Plasma Amino Acid Concentrations in Patients with Alcohol and/or Cocaine Use Disorders and Their Association with Psychiatric Comorbidity and Sex.

(1) Background: Co-occurrence of mental and substance use disorders (SUD) is prevalent, but complicates their clinical courses, and specific biomarkers are required. Amino acids are altered in primary mental disorders; however, little is known about SUD and psychiatric comorbidity. Because most psychiatric disorders and biomarkers show sex differences, we investigated amino acids in men and women with alcohol and/or cocaine use disorders (AUD and/or CUD) and psychiatric comorbidity. (2) Methods: A cross-sectional study was conducted in 295 participants, who were divided into four groups (AUD, n = 60; CUD, n = 41; AUD + CUD, n = 64; and control, n = 130). Participants were clinically assessed, and plasma amino acid concentrations were analyzed in relation to sex, diagnosis of SUD and psychiatric comorbidity (3) Results: In the total sample, there were sex differences, and women showed lower Iso, Leu, Gln and Glu than men. While patients with CUD and AUD + CUD had higher Glu, Gly, Orn and Ser than controls, patients with AUD showed no differences. In SUD, patients with psychiatric comorbidity had lower Orn and higher Ala than non-comorbid patients in the AUD group. (4) Conclusions: There was a dysregulation of plasma amino acids in abstinent patients with SUD. However, our results suggest the importance of considering the clinical characteristics and sex in the validity of amino acids as potential biomarkers for SUD.

Prognostic stratification of older patients with multivessel coronary artery disease treated with percutaneous transluminal coronary angioplasty based on clinical and biochemical measures: protocol for a prospective cohort study.

INTRODUCTION: The incidence of acute coronary syndrome is rising in step with the growth of life expectancy. An increase in the age of patients with coronary artery disease has been related to in-hospital mortality, which has seen an upsurge over a short period of time. However, there is no consensus about the percutaneous coronary angioplasty strategy to follow for older patients with multivessel coronary artery disease (MVCAD). Complete revascularisation (CR) or incomplete revascularisation (ICR) strategy depends on prognosis but this has not yet been accurately described because of geriatric conditions and comorbidities. The aim of this study is to evaluate changes of clinical and biochemical parameters in older patients with MVCAD undergoing revascularisation and to establish a prognostic stratification model for CR and ICR. METHODS AND ANALYSIS: This observational, longitudinal, prospective study will include 150 patients with MVCAD and subsequent revascularisation who attend the Hospital Universitario Virgen de la Victoria (Málaga, Spain). Because of the dropout rates, 180 patients will be recruited at the beginning. Sociodemographic characteristics, clinical and angiographic parameters, and biochemical variables, such as cardiovascular, metabolic, inflammatory, stress oxidative biomarkers, will be collected in the admission for coronary revascularisation and three follow-ups at 6, 12 and 18 months. Statistical analyses will be conducted with these data using CR and ICR as the primary exposure variable. Relevant explanatory variables will be selected from a predictive model for their inclusion in a prognostic stratification model. The primary outcome measures will be major adverse cardiovascular events. ETHICS AND DISSEMINATION: Protocols and patient information have been approved by the regional research ethics committee (CEIm Provincial de Málaga-PEIBA (PI0131/2020). The results will be disseminated in international peer-reviewed journals, presented at conferences in Cardiology and Gerontology, and sent to participants, medical and health service managers, clinicians and other researchers.

Repeated Restraint Stress and Binge Alcohol during Adolescence Induce Long-Term Effects on Anxiety-like Behavior and the Expression of the Endocannabinoid System in Male Rats.

(1) Background: Negative experiences during adolescence increase the vulnerability to develop mental disorders later in life. A better understanding of the mechanisms underlying these long-term alterations could help to identify better therapeutic interventions. (2) Methods: Adolescent male Wistar rats were used to explore the effects of repeated stress and alcohol exposure on anxiety-like behaviors, plasma corticosterone levels and the gene expression of the endocannabinoid system (ECS) and other relevant signaling systems (glutamatergic, corticotropin-releasing hormone (CRH) and neuropeptide Y (NPY)) in the amygdala and the medial prefrontal cortex (mPFC). (3) Results: Overall, both stress and alcohol induced anxiety-like behaviors, but only the alcohol-exposed rats displayed increased plasma levels of corticosterone. In the amygdala, there was a general deficit in the gene expression of the ECS and increases in the mRNA levels of certain subunits of glutamate receptors. Interestingly, there were significant interaction effects between stress and alcohol on the expression of the NMDA receptor subunits. In addition, increased mRNA levels of the CRH receptor were observed in alcohol-exposed rats. In the mPFC, alcohol exposure was associated with an increase in the gene expression of the ECS. By contrast, the combination of stress and alcohol produced opposite effects. (4) Conclusions: In summary, early stress and alcohol exposure induced long-term anxiety-like behavior in male rats but different mechanisms are involved in these maladaptive changes in the brain.

Acute stress and alcohol exposure during adolescence result in an anxious phenotype in adulthood: Role of altered glutamate/endocannabinoid transmission mechanisms.

BACKGROUND: Stressful episodes and high alcohol consumption during adolescence are considered major risk factors for the development of psychiatric disorders in adulthood. Identification of mechanisms underlying these early events, which enhanced vulnerability to mental illness, is essential for both their prevention and treatment. METHODS: Male Wistar rats were used to investigate the long-term effects of early restraint stress and intermittent alcohol exposure (intragastric administration of 3 g/kg ethanol; 4 days/week for 4 weeks during adolescence) on anxiety-like behavior and the expression of signaling systems associated with emotional behaviors [e.g., corticosterone, fatty acid-derived molecules and endocannabinoid enzymes, glutamate receptor subunits, corticotropin releasing hormone receptors (CRHR1 and CRHR2) and neuropeptide Y receptors (NPY1R and NPYR2)] in the blood and amygdala. RESULTS: Overall, both stress and alcohol exposure during adolescence induced anxiogenic-like behaviors, increased plasma levels of corticosterone and increases in the amygdalar expression of the cannabinoid CB2 receptor and certain subunits of glutamate receptors (i.e., mGluR1, mGluR5 and NMDAR1) in young adult rats. In addition, there were specific main effects of alcohol exposure on the expression of the cannabinoid CB1 receptor, monoacylglycerol lipase (MAGL) and NPY2R in the amygdala, and significant increases were observed in rats exposed to alcohol. Interestingly, there were significant interaction effects between restraint stress and alcohol exposure on the expression of plasma 2-arachidonoyl glycerol (2-AG), and both CRHR1,2 and NPY1R in the amygdala. Thus, the restraint stress was associated with increased 2-AG levels, which was not observed in rats exposed to alcohol. The alcohol exposure was associated with an increased expression of CRHR1,2 but the restraint stress prevented these increases (stress alcohol rats). In contrast, NPY1R was only increased in rats exposed to stress and alcohol. Finally, we did not observe any potentiation of the behavioral and molecular effects by the combination of stress and alcohol, which is concordant with an overall ceiling effect on some of the variables. CONCLUSION: Separate and combined early stress and alcohol induced a common anxious phenotype with increased corticosterone in adulthood. However, there were differences in the amygdalar expression of signaling systems involved in maladaptive changes in emotional behavior. Therefore, our results suggest the existence of partially different mechanisms for stress and alcohol exposures.

Panorámica de la COVID-19 en tres municipios de Guerrero, México, durante 2020 / Overview of COVID-19 in three municipalities of Guerrero, México during 2020

RESUMEN Objetivo Estimar la magnitud de daños a la salud por la pandemia de COVID-19 y su dinámica en Ometepec, Xochistlahuaca y Tlacoachistlahuaca, en Guerrero, México, durante 2020. Métodos Estudio retrospectivo hecho mediante un análisis secundario de la base de datos de COVID-19 de la Secretaría de Salud de México. Con análisis bivariado y regresión logística binaria, se desarrollaron estimaciones de series de tiempo y de magnitud del daño a la salud por COVID-19. Resultados Durante las semanas epidemiológicas 12 a 40 de 2020, se confirmaron 325 casos y 28 defunciones por COVID-19. De los casos confirmados, solo 16 % fueron indígenas. Dos de cada tres defunciones ocurrieron en las primeras 48 horas del ingreso hospitalario. Las variables predictoras que mejor se ajustaron al modelo de regresión, asociadas a la letalidad hospitalaria, fueron diabetes, neumonía asociada a COVID-19 y edad de 50 años o mayor. Conclusiones Es importante enfatizar los datos de alarma de la COVID-19 a la población indígena (en particular, la dificultad respiratoria) y factores asociados a complicaciones por COVID-19 como diabetes y edad avanzada, para incrementar el uso oportuno de los servicios de salud.

ABSTRACT Objective To estimate the magnitude and dynamics of health outcomes related to the COVID-19 pandemic and the dynamic in Ometepec, Xochistlahuaca and Tlacoachist-lahuaca in Guerrero, Mexico. Methods Retrospective study developed from the secondary analysis of the COVID-19 database, from the Mexican Ministry of Health in 2020. We developed time series and estimated the magnitude of the health effects of the pandemic by means of bivariate analysis and binary logistic regression models. Results The public health services registered 325 confirmed cases and 28 deaths from COVID-19 during epidemiologic weeks 12 to 40 in 2020. Nearly 16% of confirmed cases pertained to patients self-reported as indigenous people. Two out of three deaths occurred within 48 hours of hospital admission. Diabetes, COVID-19 pneumonia and being age 50 years or older were the predictor variables associated with hospital fatality which best fit our regression models. Conclusions It is essential to promote a greater use of government health services among indigenous populations by disseminating culturally relevant information on war-ning signs such as difficulty breathing and risk factors such as suffering from diabetes and being an older adult.

Influence of gender and education on cocaine users in an outpatient cohort in Spain.

Gender significantly influences sociodemographic, medical, psychiatric and addiction variables in cocaine outpatients. Educational level may be a protective factor showing less severe addictive disorders, longer abstinence periods, and better cognitive performance. The aim was to estimate gender-based differences and the influence of educational level on the clinical variables associated with cocaine use disorder (CUD). A total of 300 cocaine-consuming patients undergoing treatments were recruited and assessed using the Psychiatric Research Interview for Substance and Mental Diseases according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Women developed CUD later but exhibited more consumption of anxiolytics, prevalence of anxiety disorders, eating disorders, and major depressive disorders. Alcohol and cannabis use disorders were more frequent in men. A predictive model was created and identified three psychiatric variables with good prognosis for distinguishing between women and men. Principal component analysis helped to describe the different profile types of men and women who had sought treatment. Low educational levels seemed to be a risk factor for the onset, development, and duration of CUD in both genders. Women and men exhibited different clinical characteristics that should be taken into account when designing therapeutic policies. The educational level plays a protective/risk role in the onset, development and progression of CUD, thus prolonging the years of compulsory education and implementing cognitive rehabilitation programmes could be useful.