Stimuli-Specific Senescence of Primary Human Lung Fibroblasts Modulates Alveolar Stem Cell Function.

Aging is the main risk factor for chronic lung diseases (CLDs) including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Accordingly, hallmarks of aging like cellular senescence are increased in these patients in different lung cell types including fibroblasts. However, little is known about the different triggers that induce a senescence phenotype in different disease backgrounds and its role in CLD pathogenesis. Therefore, we characterized senescence in primary human lung fibroblasts (phLF) from control, IPF, or COPD patients at baseline and after exposure to disease-relevant insults (H2O2, bleomycin, TGF-ß1) and studied their capacity to support progenitor cell potential in a lung organoid model. Bulk-RNA sequencing revealed that phLF from IPF and COPD activate different transcriptional programs but share a similar senescence phenotype at baseline. Moreover, H2O2 and bleomycin but not TGF-ß1 induced senescence in phLF from different disease origins. Exposure to different triggers resulted in distinct senescence programs in phLF characterized by different SASP profiles. Finally, co-culture with bleomycin- and H2O2-treated phLF reduced the progenitor cell potential of alveolar epithelial progenitor cells. In conclusion, phLF from COPD and IPF share a conserved senescence response that varies depending on the insult and impairs alveolar epithelial progenitor capacity ex vivo.

Protocol for the Acclimatization of Coconut Vitro-Plants Under Ex Vitro Conditions.

The coconut tree is a crop widely distributed in more than 90 countries worldwide. It has a high economic value derived from the large number of products obtained from the plant, with fast-growing global markets for some of them. Unfortunately, coconut production is decreasing mainly due to the old age of the plants and devastating pests and diseases, such as phytoplasma disease lethal yellowing (LY). Massive replanting is required with phytoplasma-resistant and high-yielding selected coconut plants to keep up with the market demand for fruit. For this purpose, an efficient micropropagation technology via somatic embryogenesis has been established at CICY, yielding fully developed vitro-plants grown within an in vitro environment. Hence, the last stage of the micropropagation process is the acclimatization of the vitro-plants, which are gradually adapted to live in external conditions outside the glass container and the growth room. A protocol has been developed at CICY to acclimate the coconut vitro-plants, and close to 80% survival can be obtained. This protocol is described here.

The role of SKA2 on affective disorder, post-traumatic stress disorder and suicide behavior: systematic review and in silico analysis.

Genes involved in the hypothalamic-pituitary-adrenal axis may be a robust biomarker of psychiatric disorders. Genetic polymorphisms of the SKA2 gene are associated with several behavioral disorders. In this study, we embarked on a systematic search of all possible reports of genetic association with SKA2 and affective disorder, post-traumatic stress disorder, and suicide behavior; the functional consequences of nsSNPs were explored through computational tools with an in silico analysis. Eight eligible articles were included. Our study identified that SKA2 did not show association with risk of Major Depression Disorder. Epigenetic variation at SKA2 mediates vulnerability to Post-Traumatic Stress Disorder. Studies provide strong preliminary evidence that alterations at the SKA2 gene covary with types of suicide behavior, including suicidal ideation, attempts, and completions. Results from in silico analysis predicted that I22S, I22G, I78T, A15L, D18R, R25L, N42I, Y21S, K14I, K14L, and L60R were the most structurally and functionally significant nsSNPs in SKA2. Amino acid conservation analysis revealed that the amino acids were highly conserved and some dissimilarities of mutant type amino acids from wild-type amino acids such as charge, size, and hydrophobicity were observed. In the future, SKA2 gene have the potential to be evaluated as prognostic biomarkers for diagnosis and research.

Increased Depressive-like, Anxiety-like, and Perseverative-like Behavior in Binge Eating Model in Juvenile Rats.

The aim of the present study was to evaluate depressive-like, anxiety-like, and perseverative-like behaviors in a binge eating model. Juvenile Wistar rats, using the binge eating model, were compared to caloric restriction, induced stress, and control groups. Rats of the induced stress group presented binge-like behaviors in standard food intake in the second cycle of the experiment when compared to the caloric restriction group and the binge eating model group. Depressive-like behavior was observed in the binge eating model group with longer immobility time (p < 0.001) and less swim time (p < 0.001) in comparison to the control group. Anxiety-like behavior was observed by shorter duration of burying latency in the binge eating model group when compared to the induced stress group (p = 0.04) and a longer duration of burying time when compared to the control group (p = 0.02). We observed perseverative-like behavior by the binge model group, who made more entries to the new arm (p = 0.0004) and spent a longer time in the new arm when compared to the control group (p = 0.0001). Our results show differences in behaviors between the groups of rats studied. These results suggest that calorie restriction-refeeding, along with stress, may lead to depressive-like, anxiety-like, and perseverative-like behavioral changes in male Wistar rats.

Differential Alterations of Expression of the Serotoninergic System Genes and Mood-Related Behavior by Consumption of Aspartame or Potassium Acesulfame in Rats.

The use of aspartame (ASP) and potassium acesulfame (ACK) to reduce weight gain is growing; however, contradictory effects in body mass index control and neurobiological alterations resulting from artificial sweeteners consumption have been reported. This study aimed to evaluate the impact of the chronic consumption of ASP and ACK on mood-related behavior and the brain expression of serotonin genes in male Wistar rats. Mood-related behaviors were evaluated using the swim-forced test and defensive burying at two time points: 45 days (juvenile) and 95 days (adult) postweaning. Additionally, the mRNA expression of three serotoninergic genes (Slc6a4, Htr1a, and Htr2c) was measured in the brain areas (prefrontal cortex, hippocampus, and hypothalamus) involved in controlling mood-related behaviors. In terms of mood-related behaviors, rats consuming ACK exhibited anxiety-like behavior only during the juvenile stage. In contrast, rats consuming ASP showed a reduction in depressive-like behavior during the juvenile stage but an increase in the adult stage. The expression of Slc6a4 mRNA increased in the hippocampus of rats consuming artificial sweeteners during the juvenile stage. In the adult stage, there was an upregulation in the relative expression of Slc6a4 and Htr1a in the hypothalamus, while Htr2c expression decreased in the hippocampus of rats consuming ASP. Chronic consumption of ASP and ACK appears to have differential effects during neurodevelopmental stages in mood-related behavior, potentially mediated by alterations in serotoninergic gene expression.

Stimuli-specific senescence of primary human lung fibroblasts modulates alveolar stem cell function.

Aging is the main risk factor for chronic lung diseases (CLDs) including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Accordingly, hallmarks of aging such as cellular senescence are present in different lung cell types such as fibroblasts in these patients. However, whether the senescent phenotype of fibroblasts derived from IPF or COPD patients differs is still unknown. Therefore, we characterized senescence at baseline and after exposure to disease-relevant insults (H 2 O 2 , bleomycin, and TGF-ß1) in cultured primary human lung fibroblasts (phLF) from control donors, IPF, or COPD patients. We found that phLF from different disease-origins have a low baseline senescence. H 2 O 2 and bleomycin treatment induced a senescent phenotype in phLF, whereas TGF-ß1 had primarily a pro-fibrotic effect. Notably, we did not observe any differences in susceptibility to senescence induction in phLF based on disease origin, while exposure to different stimuli resulted in distinct senescence programs in phLF. Moreover, senescent phLF reduced colony formation efficiency of distal alveolar epithelial progenitor cells in a stimuli-dependent manner. In conclusion, the senescent phenotype of phLF is mainly determined by the senescence inducer and impairs alveolar epithelial progenitor capacity in vitro .

Development of a novel clinimetric tool: PAtient Reported Disease Activity Index in Rheumatoid Arthritis (PARDAI-RA) by PANLAR, for the assessment of patients living with rheumatoid arthritis.

BACKGROUND: Clinical experience has shown that a single measure is not sufficient to assess disease activity in rheumatoid arthritis (RA). Various clinimetric tools are necessary to address the many clinical situations that can arise. METHODS: In order to develop a comprehensive measurement tool, the Pan American League of Associations for Rheumatology searched for the most frequent measures of disease activity applied in RA by means of a semi-systematic review of the available literature. RESULTS: We found that the most frequently reported measures of disease activity were the 28-joint Disease Activity Score, C-reactive protein, and the erythrocyte sedimentation rate, followed by patient-reported measures of pain and stiffness and many other composite indices and patient-reported outcome measures. The most frequent physician-reported sign of disease was the swollen joint count, and the most frequently self-reported feature was the increase in disease activity or flares. CONCLUSION: In this article, we present a new clinimetric tool developed based on expert consensus and on data retrieved from our search. Disease activity can be better assessed by combining various data sources, such as clinical, laboratory, and self-reported outcomes. These variables were included in our novel clinimetric tool. Key Points • The goal of treatment of RA is to achieve the best possible control of inflammation, or even remission; therefore, disease management should include systematic and regular evaluation of inflammation and health status. • Clinimetric tools evaluate a series of variables (e.g., symptoms, functional capacity, disease severity, quality of life, disease progression) and can reveal substantial prognostic and therapeutic differences between patients. • Our clinimetric tool, which is based on a combination of data (e.g., clinical variables, laboratory results, PROMs), can play a relevant role in patient assessment and care.

Effects of IL-6/IL-6R axis alterations in serum, plasma and cerebrospinal fluid with the schizophrenia: an updated review and meta-analysis of 58 studies.

Studies investigating the association between IL-6/IL-6R axis and schizophrenia (SZ) susceptibility found inconsistent data. To reconcile the results, a systematic review followed by a meta-analysis was performed to assess the associations. This study followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search of the literature was carried out in July 2022 using electronic databases PubMed, EBSCO, Science Direct, PsychInfo, and Scopus. Study quality was assessed by the Newcastle-Ottawa scale. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effect or random-effect model analysis. Fifty-eight studies were identified, including 4,200 SZ patients and 4,531 controls. Our meta-analysis results showed an increase of IL-6 levels in plasma, serum, or CSF and decreased IL-6R levels in serum in patients under treatment. Further studies are needed to better elucidate the correlation between the IL-6/IL-6R axis and the schizophrenia.

The association of cytokines genes (IL-6 and IL-10) with the susceptibility to schizophrenia: A systematic review and meta-analysis.

Cytokines are among the important effectors and messenger molecules for restoring the homeostasis tissue after an inflammatory response. The association between IL-6 and IL-10 genes polymorphisms with the schizophrenia susceptibility have yielded controversial results. To reconcile the results, a systematic review followed by meta-analysis was performed to assess the association. We carried out literature searches of PubMed, Scopus, EBSCO, and Web of Sciences databases. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Subgroup analysis, heterogeneity analyses, and publication bias were also calculated in the meta-analysis. A total of 22 case-control studies, consisting of 4,993 schizophrenic patients and 5,195 healthy controls, were included in the meta-analysis. The meta-analysis suggests that the IL-6 rs1800795 polymorphism displays a protective role against schizophrenia, while the IL-10 rs1800896 and rs1800872 polymorphisms confer an increased risk of schizophrenia. Similar results were found in subgroup analysis by ethnicity. We did not find association between IL-10 rs1800871 polymorphism and schizophrenia susceptibility. Finally, this meta-analysis suggested that the dysregulation of cytokines could lead to the pathogenesis of the schizophrenia.

Joint effect of heat, pH and grape extract on Bacillus cereus spores survival in a rice solution.

Rice due to its high carbohydrate content, is an ideal medium for Bacillus cereus growth, a spore-producing microorganism. The objective of this study was to determine the antimicrobial activity of a grape extract in combination with heat treatments and different pH against B. cereus spores in a rice solution. The survivor data obtained were fitted to the Weibull survival function, and the values of parameters a and b (scale and shape indexes, respectively) were determined. Results showed that the grape extract affected the survival of B. cereus spores at 90 °C and 95 °C, reaching greater logarithmic reductions in acidic pH values. This behaviour was reflected in a parameter of the Weibull survival function which decreased as the temperature increased and at acidic pH values. In addition, a secondary model was developed by relating the logarithm of a to the independent variables (temperature and pH). A global model relating B. cereus inactivation with temperature and pH was developed, and validated by calculating the accuracy factor. The results demonstrate the usefulness of grape extract as a by-product, which can be used as an additional control measure for rice, especially when combined with mild heat treatments and acidic pH values.

Aggression against Nursing Personnel during the First Wave of COVID-19 Pandemic: An Internet-Based Survey.

(1) Background: health care workers, particularly nurses, have been regularly assaulted during the COVID-19 pandemic. Purpose: to evaluate the prevalence and location of assaults against nursing personnel in Latin America, and to determine predictor factors for aggression against nurses. (2) Methods: A cross-sectional online survey was answered by 374 nurses working in health care during the COVID-19 pandemic. The aggression against nurses was estimated using the Victimization Scale. (3) Results: A total of 288 nurses were included in this study. The victimization scale showed that 52.1% of nurses have suffered aggression by the general population during the COVID-19 pandemic. Males were more likely to be attacked than females (p < 0.05). Additionally, males were attacked more frequently on public transport (x2 = 6.72, p = 0.01). The home neighborhood and markets were other locations with a higher risk of being assaulted (OR: 3.39, CI: 1.53-7.50). (4) Conclusions: Our results indicate that nurses in Latin America who work during the COVID-19 pandemic and social isolation have been frequently assaulted by the general public. Males are more frequently attacked than females and the main places of aggression are public transportation, their home neighborhood and supermarkets. Implications for nursing practice: it is necessary to create and implement protocols and guidelines to support nursing personnel during the COVID-19 pandemic. This study was retrospectively registered at the Juarez Autonomous University of Tabasco (103/CIPDACS/2020) on the (08/2020).

Prevalence of Poor Sleep Quality and Associated Factors in Individuals with Rheumatoid Arthritis: A Cross-Sectional Study.

Background and Objectives: Poor sleep quality has been frequently observed in individuals with rheumatoid arthritis. In the present study, we analyzed the presence of poor sleep quality in a sample of Mexican individuals with rheumatoid arthritis; then, we compared sociodemographic and clinical characteristics among patients to determine risk factors for poor sleep quality. Materials and Methods: In this cross-sectional study, we included 102 individuals with rheumatoid arthritis from a hospital in Mexico. We evaluated disease activity (DAS28), quality of sleep using the Pittsburgh Sleep Quality Index, and the presence of depression and anxiety with the Hospital Anxiety and Depression Scale. We performed a Chi-square test and a t-test. Then, we performed a logistic regressions model of the associated features in a univariable analysis. Results: Poor sleep quality was observed in 41.75% of the individuals with rheumatoid arthritis. Being married was a proactive factor (OR 0.04, 95% CI 0.1-0.9, p = 0.04), whereas having one's hips affected or presenting with anxiety and depression was associated with poor sleep quality (OR 4.6, 95% CI 1.2-17.69, p = 0.02). After a multivariate analysis, having anxiety (OR 5.0, 95% CI 1.4-17.7, p < 0.01) and depression (OR 9.2, 95% CI 1.0-8.1, p < 0.01) remained associated with a higher risk of having poor sleep quality. Other clinical characteristics among patients were not significantly different. Conclusions: Our results showed that individuals with rheumatoid arthritis who also presented with depression or anxiety had a higher risk of suffering from poor sleep quality. However, more studies with larger samples are necessary to replicate these results in the Mexican population.

Diseño y Validación de una Aplicación Móvil, para el Diagnóstico de Anemia en Pre-Escolares. Estudio de Precisión Diagnóstica / Design and Validation of a Mobile Application for the Diagnosis of Anemia in Preschoolers. Diagnostic Accuracy Study

La anemia afecta a miles de niños. Para el diagnóstico se cuantifica la hemoglobina (Hb); técnica que no se encuentra al alcance de toda la población. Contar con un instrumento validado de fácil aplicación, puede ayudar al diagnóstico. El objetivo de este estudio fue validar una aplicación móvil (APP) para diagnosticar anemia en niños de 2 a 5 años, aplicable por padres o tutores. Estudio de validación de escalas. Mediante búsqueda bibliografía se recopilaron ítems y dominios relacionados con anemia en niños. Una vez reducidos, se construyó un cuestionario para pilotaje, con tres hematólogos pediatras. El resultado de este fue posteriormente validado por 22 expertos mediante aplicación de escalas tipo Likert. Los ítems validados, se contrastaron con la Hb de niños de 267 niños de 2 a 5 años de los andes ecuatorianos (2.560 msnm). Se determinó asociación de los ítems con Hb y con los resultados obtenidos y se construyó la APP. 14 ítems fueron analizados. Todos ellos puntuaron sobre la mediana de la distribución (35,5 puntos) y fueron valorados por, al menos el 50 % de los expertos. Se seleccionaron palidez palmar, astenia y sueño en horas no habituales. Todos mostraron asociación significativa con anemia (p<0,05), y fueron aplicados como preguntas a padres o tutores y contrastados con el valor de Hb. Sensibilidad y especificidad para palidez fue: 85,1 % y 85,0 %; astenia: 72,3 % y 87,7 %; sueño en horas no habituales: 68,1 % y 87,7 %; palidez más astenia o sueño: 95,7 % y 74,6 %; y debilidad más sueño: 92,5 % y 76,8 %. Se desarrolló y validó una APP para diagnóstico de anemia en niños de 2 a 5 años aplicable por padres o tutores.

SUMMARY: Anemia affects thousands of children, and to reach a diagnosis, hemoglobin (Hb) is quantified. This technique however, is not always accessible to the general population. Therefore, the availability of a validated instrument can be useful in the diagnosis. The aim of this study was to validate a mobile application (APP), to diagnose anemia in children from 2 to 5 years old, applicable by parents or guardians. Scale validation study. Through a bibliographic search, items and domains related to anemia in children were collected. Once reduced, a pilot questionnaire was constructed with three pediatric hematologists. The result was later validated by 22 experts through the application of the Likert-type scales. The validated items were contrasted with the Hb of children of 267 children from 2 to 5 years of age from the Ecuadorian Andes (2,560 meters above sea level). The association of the items with Hb and with the results obtained was determined, and the APP was constructed. 14 items were analyzed. All of them scored above the median of the distribution (35.5 points) and were valued by at least 50 % of the experts. Palmar pallor, asthenia, and sleep at unusual hours were selected. All showed a significant association with anemia (p<0.05) and were applied as questions to parents or guardians and contrasted with the Hb value. Sensitivity and specificity for pallor was: 85.1 % and 85.0 %; asthenia: 72.3 % and 87.7 %; sleep at unusual hours: 68.1 % and 87.7 %; paleness plus fatigue or sleepiness: 95.7 % and 74.6 %; and weakness plus sleep: 92.5 % and 76.8 %. An APP for the diagnosis of anemia in children from 2 to 5 years old applicable by parents or guardians was developed and validated.

Desacylghrelin modulates GHS-R1 receptor expression and cell differentiation in placental BeWo cells.

BACKGROUND: and purpose: Ghrelin is the endogenous ligand of the growth hormone secretagogue receptor (GHS-R1). Ghrelin, and GHS-R1, may have a role in placental growth and function, and its unacylated form desacylghrelin (DAG) could be involved in fetal growth. Nevertheless, the effects of DAG on placental function, and the receptor involved in its actions, remain to be determined. We aimed to investigate the effect of DAG in placental BeWo cells viability, proliferation, differentiation, and GSH-R1 expression. METHODS: BeWo cells, a human trophoblast cell line, was cultured with 3 nM DAG during 12, 24, 48, and 72 h. Cell viability, proliferation, differentiation (assessed by human Chorionic Gonadotropin quantification), and GSH-R1 expression were analyzed. To evaluate the mechanism of DAG effect on GSH-R1, 30 nM receptor antagonist ([D-Lys3]-GHRP-6) was added alone or in combination with 3 nM DAG during 12 h and 24 h. RESULTS: DAG has no effect on cell proliferation or viability, but it has an inhibitory effect on cell differentiation. DAG had a stimulatory effect on GSH-R1 expression at 12 and 24 h (p = 0.029 and p = 0.025, respectively). On the contrary, culture with 48 h DAG inhibits GSH-R1 expression compared to the control (p = 0.005), while GSH-R1 antagonist inhibited the effect of DAG on GSH-R1 expression. DAG also reduces intracellular (p = 0.020) and secreted (p = 0.011) hCG concentration in BeWo cells. CONCLUSION: DAG increases GHS-R1 expression, potentially mediated through GHS-R1 itself. DAG may also inhibit placental BeWo cell differentiation, suggesting a possible role of DAG in placental and fetal physiology.

Gene Expression Analysis in Postmortem Brains from Individuals Who Died by Suicide: A Systematic Review.

Around the world, more the 700,000 individuals die by suicide every year. It is necessary to understand the mechanisms associated with suicidal behavior. Recently, an increase in gene expression studies has been in development. Through a systematic review, we aimed to find a candidate gene in gene expression studies on postmortem brains of suicide completers. Databases were systematically searched for published studies. We performed an online search using PubMed, Scopus and Web of Science databases to search studies up until May 2023. The terms included were "gene expression", "expressed genes", "microarray", "qRT-PCR", "brain samples" and "suicide". Our systematic review included 59 studies covering the analysis of 1450 brain tissues from individuals who died by suicide. The majority of gene expression profiles were obtained of the prefrontal cortex, anterior cingulate cortex, dorsolateral prefrontal cortex, ventral prefrontal cortex and orbital frontal cortex area. The most studied mRNAs came of genes in glutamate, γ-amino-butyric acid and polyamine systems. mRNAs of genes in the brain-derived neurotrophic factor, tropomyosin-related kinase B (TrkB), HPA axis and chemokine family were also studied. On the other hand, psychiatric comorbidities indicate that suicide by violent death can alter the profile of mRNA expression.

Gene-environment interaction between HPA-axis genes and trauma exposure in the suicide behavior: A systematic review.

Suicide behavior (SB) emerge from complex interactions among traumatic events and multiple genetic factors. We conducted the first systematic review to assess the evidence of a link among trauma exposure, HPA-axis genes, and SB. A systematic search of PubMed, EBSCO, Science Direct, PsychInfo, and Scopus databases on gene-environment interaction, and susceptibility to SB was carried out until February 2022. Our study was prospectively registered in PROSPERO (CRD42022316141). A total of 13 epidemiological studies (11,756 subjects) were included: eight studies focused on traumatic experiences in the childhood and five studies on lifetime trauma exposure. All studies reported a positive association between the trauma exposure with SB. Gene-environment interaction was reported for CRHR1 (n = 6), CRHR2 (n = 2), FKBP5 (n = 2), and CRHBP (n = 1), however, for CRH, NR3C1, MC2R, and POMC genes no found gene-environment effects on SB. Trauma exposure could be one mechanism that links HPA-axis genes activity with the development of SB.

DNA Methylation of Genes Involved in the HPA Axis in Presence of Suicide Behavior: A Systematic Review.

DNA methylation in genes of the hypothalamic-pituitary-adrenal (HPA) axis has been associated with suicide behavior. Through a systematic review, we aimed to evaluate DNA methylation levels of the genes involved in the HPA pathway and their association with suicide behavior. A search of articles was performed using PubMed and Science Direct, EBSCO. The terms included were "DNA methylation", "suicide", "epigenetics", "HPA axis" and "suicide behavior". This systematic review was performed by the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. Six studies comprising 743 cases and 761 controls were included in this systematic review. The studies included individuals with suicide ideation, suicide attempts or completed suicide and childhood trauma, post-traumatic stress disorder (PTSD), or depression. One study reported hypermethylation in GR in childhood trauma, while two studies found hypermethylation of NR3C1 in childhood trauma and major depressive disorder (MDD). Only one study reported hypermethylation in BNDF in people with MDD. FKBP5 was found to be hypermethylated in people with MDD. Another study reported hypermethylation in CRHBP. SKA2 was reported to be hypermethylated in one study and another study found hypomethylated both in populations with PTSD. CRHR1 was found to be hypermethylated in people with MDD, and the last study found hypomethylation in CRH. Our result showed that patients with suicidal behavior showed a DNA methylation state of genes of the HPA axis in association with psychiatric comorbidity and with adverse events. Genes of the HPA axis could play a role in suicidal behavior associated with adverse events and pathologies. As a result, DNA methylation levels, proteins, and genes involved in the HPA axis could be considered for the search for biomarkers for the prevention of suicidal behavior in future studies.

Association between Genetic Variants of CELSR2-PSRC1-SORT1 and Cardiovascular Diseases: A Systematic Review and Meta-Analysis.

A cluster of three genes CELSR2, PSRC1, and SORT1 has been associated with cardiovascular diseases. Thus, the aim of this study was (i) to perform a systematic review and updated meta-analysis of the association of three polymorphisms (rs646776, rs599839, and rs464218) of this cluster with cardiovascular diseases, and (ii) to explore by PheWAS signals of the three SNPs in cardiovascular diseases and to evaluate the effect of rs599839 with tissue expression by in silico tools. Three electronic databases were searched to identify eligible studies. The meta-analysis showed that the rs599839 (allelic OR 1.19, 95% CI 1.13-1.26, dominant OR 1.22, 95% CI 1.06-1.39, recessive OR 1.23, 95% CI 1.15-1.32), rs646776 (allelic OR 1.46, 95% CI 1.17-1.82) polymorphisms showed an increased risk for cardiovascular diseases. PheWas analysis showed associations with coronary artery disease and total cholesterol. Our results suggest a possible involvement of the CELSR2-PSRC1-SORT1 cluster variants in the risk association of cardiovascular diseases, particularly coronary artery disease.

Chronic Pain and Depression are Increased in Outpatient Adults with Somatic Symptoms from Secondary Health Care Services.

BACKGROUND: Somatic symptom disorder is described as excessive thoughts, feelings, or behaviors related to physical symptoms. The presence of somatic symptoms has been associated with depression, alexithymia, and the presence of chronic pain. Individuals with somatic symptom disorder are frequent attenders of primary health care services. AIM: We focused on investigating if the presence of psychological symptoms, alexithymia, or pain could be risk factors for somatic symptoms in a secondary health care service. METHODS: A cross-sectional and observational study. A total of 136 Mexican individuals who regularly attend a secondary health care service were recruited. The Visual Analogue Scale for Pain Assessment, the Symptom Checklist 90, and the Patient Health Questionnaire-15 were applied. RESULTS: Of all the participants, 45.2% showed somatic symptoms. We observed that these individuals more frequently presented with complaints of pain (χ2 = 18.4, p < .001), as well as more severe (t = -4.6, p < .001), and prolonged (χ2 = 4.9, p = 0.02). They also exhibited higher severity in all psychological dimensions assessed (p < .001). Finally, cardiovascular disease (t = 2.52, p = .01), pain intensity (t = 2.94, p = .005), and SCL-90 depression (t = 7.58, p < .001) were associated with somatic symptoms. CONCLUSIONS: In this study, we observed a high frequency of somatic symptoms in outpatients attending secondary health care services. They may be accompanied by comorbid cardiovascular conditions, higher pain intensity, and other mental health-related symptoms, which may aggravate the general clinical picture presented by the patient seeking health care. The presence and severity of somatization should be taken into consideration in the first and second level health care services for an early mental state evaluation and treatment of these outpatients to have a better clinical assessment and health outcome.

Effect of risperidone on serum IL-6 levels in individuals with schizophrenia: a systematic review and meta-analysis.

BACKGROUND: Risperidone has been significant correlated with a direct effect of interleukin-6 (IL-6) levels in patients with schizophrenia. This fact allows the opportunity to link the probable immunomodulatory effect of antipsychotic medication. Specially, a proper functioning of IL-6 pathway plays a potential role in the treatment or development of schizophrenia. OBJECTIVE: Our primary aim was to perform a systematic review and meta-analysis to determine the effect of risperidone on IL-6 levels in individuals with schizophrenia. METHODS: Studies were identified through a systematic search using PubMed, Scopus, and Web of Science databases. The articles found were subjected to the inclusion and exclusion criteria; then, the mean and standardised differences were extracted to calculate the standardised mean differences using the CMA software. RESULTS: IL-6 levels in individuals with schizophrenia were compared before and after receiving risperidone as treatment. Increased levels of IL-6 levels were observed in individuals with schizophrenia who received risperidone (point estimate 0.249, lower limit 0.042, upper limit 0.455, p-value 0.018). In the Asian population sub-analysis, no statistically significant differences were observed (point estimate 0.103, lower limit -0.187, upper limit 0.215, p value 0.890). When we compared individuals with schizophrenia to the control groups, a significant increase of IL-6 levels was observed in the group with schizophrenia (point estimate 0.248, lower limit 0.024, upper limit 0.472, p-value 0.30). CONCLUSIONS: Risperidone appears to play an important role in IL-6 levels in schizophrenia. Potential implications of increased IL-6 levels in people with schizophrenia should be considered in future studies.KEY POINTSIncreased levels of IL-6 levels were observed in individuals with schizophrenia who received risperidone.Risperidone appears to play an important role in IL-6 levels in schizophrenia.This study could serve for future research focussed on IL-6.