Effects of Executive Functions and Cognitive Variables in Experimentally Induced Acute Pain Perception during a Distraction Task: A Study on Asymptomatic Pain-Free Individuals.

The aim of this study was to investigate the influence of executive functioning and cognitive performance on individual experimentally induced pain perception during distractor tasks in an asymptomatic pain-free population. A total of 59 healthy pain-free subjects (59.3% women, mean age: 46.5 ± 24.7 years) completed a battery test that assessed execution functions (cognitive flexibility, working memory, mental inhibition), attention level, and psychological aspects (anxiety/depressive levels-HADS, pain catastrophizing-PCS, pain anxiety symptoms-PASS 20, sleep quality-PSQI) before conducting two n-back distraction tasks. Pain was experimentally induced with a thermal stimulus that was able to induce moderate pain (70/100 points) and applied to the non-dominant forearm. The thermal stimulus was applied before and during both (one-back and two-back) distraction tasks. The analyses consisted of separated repeated-measures ANOVA that considered the functioning on each test (cognitive flexibility, working memory, mental inhibition, selective attention) and controlled for sociodemographic and psychological aspects by comparing the pain intensity at the baseline and during the one-back and two-back distractor tasks. All ANOVAs found a significant effect of the distraction task, which indicates that the perceived pain intensity scores were lower during the one-back and two-back tasks (p < 0.001) as compared with the baseline. No interaction effect between the distractor tasks and working memory (p = 0.546), mental inhibition (p = 0.16), cognitive flexibility (p = 0.069), or selective attention (p = 0.105) was identified. The current study found that a distraction task decreased the perceived intensity of experimentally induced pain in asymptomatic pain-free individuals and that this effect was not related to executive function or attention levels.

Understanding the Associations between Executive Function and Psychological Variables in Fibromyalgia Syndrome: A Network Analysis Approach.

The aim of this study was to quantify the multivariate relationships between clinical, cognitive performance, executive functioning, and psychological outcomes in women with fibromyalgia (FMS) using network analyses. Demographic (age, height, weight), clinical (pain history, pain intensity, and related disability), neurocognitive (D2 Attention test, Rey-Osterrieth Complex Figure for visual perception, "Digits D/R/I" tests of the WAIS-IV battery for working memory, the 5-Digit Test for mental inhibition, the Symbol Search for processing speed and the Zoo Test for planning/decision making) and psychological (depressive symptoms, anxiety levels, sleep quality, pain hypervigilance) variables were collected in 129 women with FMS and 111 healthy women. Network analyses were conducted separately for each group to quantify the adjusted correlations between the modeled variables and to assess their centrality indices (i.e., connectivity with other symptoms in the network and their importance in the network). The network identified 74 associations in FMS women and 46 associations in controls with small differences. The strongest correlations in both groups were found between different attention variables: d2_CON with d2_C, d2_O with d_2TR, and d2_CON with d2_TA. The most central variables were d2_TA, d2_C, and d2_CON (highest strength centrality in both groups) and anxiety levels and pain hypervigilance (highest harmonic centrality in FMS women). The strength centrality of the network was stable for women with FMS (CScor0.7: 0.68) but not for healthy women (CScor0.7: 0.28). This study found that attention variables are most relevant within a neurocognitive network and that psychological variables are most important for the treatment of women with FMS. The clinical implications of the current findings, such as the development of treatments targeting these variables, are discussed.

Endoscopic Characterization of Giant Choledocholithiasis and Its Correlation With Primary Choledocholithiasis.

INTRODUCTION: Gallstone disease is extremely prevalent in Western society, and the prevalence of common bile duct (CBD) stones with concomitant cholelithiasis increases significantly in the elderly. Different variants influence the treatment of this pathological entity, such as the origin of the stones, their location and quantity, comorbidities of the patient, impaction, and size of the lithos, the latter being an independent predictive factor. In most situations, choledocholithiasis can be resolved with endoscopic retrograde cholangiopancreatography (ERCP); however, in complex cases, such as giant choledocholithiasis (GC), advanced surgical, endoscopic, and percutaneous techniques are required to remove gallstones. The main objective was to determine if there is a correlation between GC and primary choledocholithiasis (PC). The secondary objective consisted of describing the endoscopic characterization of GC. METHODS:  The present study is a cross-sectional and single-center study. The study population consisted of patients of the Institute for Social Security and Services for State Workers (ISSSTE by its acronym in Spanish) Regional Hospital, León, Guanajuato, belonging directly to this center or referred, who required medical attention by the General Surgery/Endoscopy Service with the diagnosis of choledocholithiasis, during the period between January 2017 and December 2022. The Kolmogorov-Smirnov test was used as the normality test. Quantitative variables were reported as mean and standard deviation if the data distribution was normal, in contrast with the expression of data in the median and interquartile range if an abnormal distribution was found. Moreover, the qualitative variables are reported in frequencies or percentages. The Chi-square test was performed as the independence test. The significance level was a 95% confidence interval (p-value 0.05). The effect size was calculated with the odds ratio (OR). RESULTS:  Out of a total of 177 patients, 33 corresponded to PC (18.6%), and 144 belonged to the secondary choledocholithiasis (SC) group (81.4%). Likewise, regarding the dimensions of the lithos, 59 patients (33.3%) presented GC and 118 (66.7%) presented non-GC. Among the 59 patients with GC, 36 were female (61%) and 23 were male (39%). Regarding age, the distribution was as follows: mean 62 ± 12 years, with a minimum value of 29 and a maximum of 88 years. The non-parametric test used to determine the existence or not of a correlation between the variables was Pearson's Chi-square, whose value was 60.509, with a p < 0.001, demonstrating the presence of a correlation between PC and GC. The effect size was corroborated and defined with the OR, whose value was 39.6 (confidence interval (CI) 11.308-139.069). CONCLUSIONS:  There is a significant correlation between GC and PC, and it was found that mechanical lithotripsy was the most performed initial extraction method for GC; furthermore, a higher rate of complete endoscopic resolution was found, as well as no complications related to the procedure, which contrasts with the literature. It would be interesting to use the information revealed in the present study as a landmark in future research in this regard.

Assessment of the role of high-density lipoproteins and their immunomodulatory activity in systemic lupus erythematosus immunopathology.

OBJECTIVE: To explore the potential associations between high-density lipoprotein (HDL) levels and inflammasome components in the context of systemic lupus erythematosus (SLE). METHODS: A cross-sectional study was conducted. A group of 50 patients with SLE and 50 healthy controls matched by sex and similar age ranges were enrolled. Serum HDL cholesterol (HDL-C) and C reactive protein (CRP) levels were quantified. Serum cytokine levels, including IL-1ß and IL-6, were determined by ELISA. The gene expression of inflammasome-related genes in peripheral blood mononuclear cells was measured by quantitative real-time PCR. RESULTS: HDL-C levels were lower in the patients with SLE (p<0.05), and on segregation according to disease activity, those with active SLE had the lowest HDL-C levels. Patients with SLE presented higher concentrations of the serum inflammatory cytokines IL-1ß and IL-6 (p<0.0001) but similar levels of CRP to those in controls. A similar scenario was observed for the gene expression of inflammasome components, where all the evaluated markers were significantly upregulated in the SLE population. These results revealed significant negative correlations between HDL levels and disease activity, serum IL-6 and IL-1ß levels and the mRNA expression of NLRP3, IL-1ß and IL-18. In addition, significant positive correlations were found between disease activity and serum IL-1ß and between disease activity and the mRNA expression of IL-18, and interestingly, significant positive correlations were also observed between active SLE and serum IL-1ß and the mRNA expression of NLRP3. CONCLUSION: Our results suggest that HDL is essential for SLE beyond atherosclerosis and is related to inflammation regulation, possibly mediated by inflammasome immunomodulation.

Exploring the Association Between Systemic Lupus Erythematosus and High-Density Lipoproteins: A Systematic Review and Meta-Analysis.

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease with inflammation as a critical feature. Recently, high-density lipoprotein cholesterol (HDLc) have been evidenced to have anti-inflammatory effects, suggesting a potential link between HDL and SLE that needs to be thoroughly studied. The aim was to explore the association between SLE and HDLc through a systematic review with meta-analysis. METHODS: A systematic review with meta-analysis was conducted to assess mean differences in HDL levels between patients with SLE and healthy controls. Both qualitative and quantitative syntheses were performed, including an assessment of heterogeneity using I2, a publication bias evaluation, a methodologic quality assessment, and a forest plot under a random effects model. Subgroup analyses were conducted based on disease activity and the report of corticosteroid dosage. RESULTS: A total of 53 studies were included in the qualitative synthesis, and 35 studies were included in the quantitative synthesis, comprising 3,002 patients with SLE and 2,123 healthy controls. Mean HDL levels were found to be lower in patients with SLE as follows: in the meta-analysis including all articles -6.55 (95% confidence interval [CI] -8.77 to -4.33); in patients with mild disease activity -5.46 (95% CI -8.26 to -2.65); in patients with moderate or severe disease activity -9.42 (95% CI -15.49 to -3.34); in patients using corticosteroids -5.32 (95% CI -10.35 to -0.29); and in studies with excellent methodologic quality -8.71 (95% CI -12.38 to -5.03). CONCLUSION: HDL levels appear to be quantitatively altered in patients with SLE, suggesting a potential contribution to immune dysregulation, highlighting the importance of HDL in autoimmune diseases.

Coarse particulate matter (PM10) induce an inflammatory response through the NLRP3 activation.

INTRODUCTION: PM exposure can induce inflammatory and oxidative responses; however, differences in these adverse effects have been reported depending on the chemical composition and size. Moreover, inflammatory mechanisms such as NLRP3 activation by PM10 have yet to be explored. OBJECTIVE: To assess the impact of PM10 on cell cytotoxicity and the inflammatory response through in vitro and in vivo models. METHODOLOGY: Peripheral blood mononuclear cells (PBMCs) from healthy donors were exposed to PM10. Cytotoxicity was determined using the LDH assay; the expression of inflammasome components and the production of pro-inflammatory cytokines were quantified through qPCR and ELISA, respectively; and the formation of ASC complexes was examined using confocal microscopy. For in vivo analysis, male C57BL6 mice were intranasally challenged with PM10 and bronchoalveolar lavage fluid was collected to determine cell counts and quantification of pro-inflammatory cytokines by ELISA. RNA was extracted from lung tissue, and the gene expression of inflammatory mediators was quantified. RESULTS: PM10 exposure induced significant cytotoxicity at concentrations over 100 µg/mL. Moreover, PM10 enhances the gene expression and release of pro-inflammatory cytokines in PBMCs, particularly IL-1ß; and induces the formation of ASC complexes in a dose-dependent manner. In vivo, PM10 exposure led to cell recruitment to the lungs, which was characterized by a significant increase in polymorphonuclear cells compared to control animals. Furthermore, PM10 induces the expression of several inflammatory response-related genes, such as NLRP3, IL-1ß and IL-18, within lung tissue. CONCLUSION: Briefly, PM10 exposure reduced the viability of primary cells and triggered an inflammatory response, involving NLRP3 inflammasome activation and the subsequent production of IL-1ß. Moreover, PM10 induces the recruitment of cells to the lung and the expression of multiple cytokines; this phenomenon could contribute to epithelial damage and, thus to the development and exacerbation of respiratory diseases such as viral infections.

Evaluation of Cognitive Performance in Patients with Fibromyalgia Syndrome: A Case-Control Study.

Patients with fibromyalgia syndrome tend to report deficits in cognitive functions; however, there is no clear consensus on which cognitive domains are impaired. The aim of this study was to compare the differences in cognitive performance between a group of patients with fibromyalgia syndrome and a group of pain-free subjects controlling for the covariables anxiety, depression, and sleep quality. In total, 130 patients with fibromyalgia syndrome and 111 pain-free subjects with an average age of 54.96 years completed the evaluation protocol consisting of sociodemographic data, psychological data, and neurocognitive tests. All data were collected from May 2022 to May 2023. Multivariate analyses of covariance (MANCOVAs) were conducted to assess intergroup differences in all neurocognitive tests. MANCOVA analyses showed that the group of patients with fibromyalgia showed a worse cognitive performance than the group of pain-free subjects after controlling for anxiety, depression, and sleep quality. This study found that fibromyalgia patients exhibited worse cognitive performance and executive function than pain-free subjects. Thus, cognitive performance seems to not be related with anxiety, depression, or sleep quality in our sample of women with FMS.

Effectiveness of Drug Repurposing and Natural Products Against SARS-CoV-2: A Comprehensive Review.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a betacoronavirus responsible for the COVID-19 pandemic, causing respiratory disorders, and even death in some individuals, if not appropriately treated in time. To face the pandemic, preventive measures have been taken against contagions and the application of vaccines to prevent severe disease and death cases. For the COVID-19 treatment, antiviral, antiparasitic, anticoagulant and other drugs have been reused due to limited specific medicaments for the disease. Drug repurposing is an emerging strategy with therapies that have already tested safe in humans. One promising alternative for systematic experimental screening of a vast pool of compounds is computational drug repurposing (in silico assay). Using these tools, new uses for approved drugs such as chloroquine, hydroxychloroquine, ivermectin, zidovudine, ribavirin, lamivudine, remdesivir, lopinavir and tenofovir/emtricitabine have been conducted, showing effectiveness in vitro and in silico against SARS-CoV-2 and some of these, also in clinical trials. Additionally, therapeutic options have been sought in natural products (terpenoids, alkaloids, saponins and phenolics) with promising in vitro and in silico results for use in COVID-19 disease. Among these, the most studied are resveratrol, quercetin, hesperidin, curcumin, myricetin and betulinic acid, which were proposed as SARS-CoV-2 inhibitors. Among the drugs reused to control the SARS-CoV2, better results have been observed for remdesivir in hospitalized patients and outpatients. Regarding natural products, resveratrol, curcumin, and quercetin have demonstrated in vitro antiviral activity against SARS-CoV-2 and in vivo, a nebulized formulation has demonstrated to alleviate the respiratory symptoms of COVID-19. This review shows the evidence of drug repurposing efficacy and the potential use of natural products as a treatment for COVID-19. For this, a search was carried out in PubMed, SciELO and ScienceDirect databases for articles about drugs approved or under study and natural compounds recognized for their antiviral activity against SARS-CoV-2.

Integrase inhibitors: current protagonists in antiretroviral therapy.

Since HIV was identified as the etiological agent of AIDS, there have been significant advances in antiretroviral therapy (ART) that has reduced morbidity/mortality. Still, the viral genome's high mutation rate, suboptimal ART regimens, incomplete adherence to therapy and poor control of the viral load generate variants resistant to multiple drugs. Licensing over 30 anti-HIV drugs worldwide, including integrase inhibitors, has marked a milestone since they are potent and well-tolerated drugs. In addition, they favor a faster recovery of CD4+ T cells. They also increase the diversity profile of the gut microbiota and reduce inflammatory markers. All of these highlight the importance of including them in different ART regimens.

Research on HIV/AIDS has been focused on finding ways to prevent or cure the disease. One important class of drugs called integrase inhibitors has gained attention. These drugs are effective and have been widely used in the past decade to treat HIV. Integrase inhibitors help in the recovery of immune cells and improve the diversity of gut bacteria while reducing inflammation. It is important to include these drugs in treatment regimens for people living with HIV.

NK cells from Men Who Have Sex with Men at high risk for HIV-1 infection exhibit higher effector capacity.

Despite being under constant exposure to HIV-1, some individuals do not show serological or clinical evidence of infection and are known as HESN (HIV-Exposed Seronegative). Multiple studies in different HESN cohorts have linked the NK cells as a correlate of resistance; however, little is known about the role of these cells in Men Who Have Sex with Men (MSM) with high risk sexual behaviors. We evaluated a general overview of activation and effector features of NK cells of MSM co-cultured with LT CD4+ HIV+ in which MSM at high risk of HIV-1 infection (HR-MSM) exhibit higher capacity to eliminate infected cells, reduced percentages of CD69+ cells when compared to MSM at low risk of infection (LR-MSM). In addition, we found that, despite the lower levels of CD69+ NK cells on HR-MSM group, within this population, higher percentages of CD69+ IFN-γ+ and CD69+ NKG2D+ NK cells were found together with higher levels of RANTES and Granzyme B production with higher antiviral capacity, resulting in a lower concentration of p24 protein and p24+ CD4+ T cells. Altogether, this information suggests that NK cells of MSM could impact the capacity to face the viral infection.

Multilevel prenatal socioeconomic predictors of Mexican American children's cardiometabolic health in preschool and school age.

OBJECTIVE: Using a life course perspective, this longitudinal study examines the extent to which prenatal family- and neighborhood-level socioeconomic factors influence the cardiometabolic health of low-income Mexican American children. It was hypothesized that prenatal maternal residence in a more economically disadvantaged neighborhood and more family-level economic hardship would each be associated with higher adiposity and blood pressure (BP) at child age 4.5 years, and higher adiposity, BP, inflammation and a less healthy lipid profile at child age 7.5 years. METHOD: The sample consisted of 322 low-income, Mexican American mother-child dyads, 181 of whom completed the 7.5-year laboratory visit. Using maternal prenatal residence and U.S. census data, neighborhood concentrated disadvantage index was computed. RESULTS: Higher prenatal neighborhood concentrated disadvantage predicted higher 4.5-year adiposity in children, which, in turn, predicted higher adiposity, BP, and inflammation, and less healthy lipid profile (higher triglycerides, lower high-density lipoprotein cholesterol) at 7.5 years. Higher child 4.5-year BP was concurrently associated with higher adiposity and predicted higher 7.5-year BP. CONCLUSIONS: Extending previous work with this sample, the current study found associations between cardiometabolic risk indicators as early as preschool among Mexican American children. Furthermore, this study builds on existing literature by expanding our understanding of the effect of prenatal neighborhood concentrated disadvantage on cardiometabolic phenotypes during early childhood. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Guillain-Barre syndrome before and during the COVID-19 pandemic in a referral center of Mexico.

BACKGROUND: During the COVID-19 pandemic, an increase in the number of Guillain-Barre syndrome (GBS) cases has been reported. OBJECTIVE: To describe the clinical characteristics and prognosis of patients with GBS before and during the COVID-19 pandemic. MATERIAL AND METHODS: Prospective cohort of GBS patients divided in two subgroups: before (2018-2019) and during (2020-2021) the COVID-19 pandemic. Clinical and paraclinical characteristics, as well as deaths, were recorded. A good prognosis was defined as independent ambulation recovery at three months. RESULTS: Two-hundred and one patients were included (123 during and 78 before the pandemic), out of whom 69% were males; age was 45 ± 16 years, and there was 2.5% of in-hospital deaths. During the pandemic, a higher frequency of the demyelinating variant (50%), bulbar cranial nerves involvement (44% vs. 28%), prior history of vaccination (16% vs. 0%), and a lower MRC score (30 ± 16.7 vs. 34.3 ± 17.7) were documented. An increase in the number of cases was observed from July to September (38 vs. 13). There were no significant differences in independent ambulation recovery or in the number of deaths. CONCLUSIONS: During the COVID-19 pandemic, a higher number of GBS cases were treated, out of which 16% were associated with the SARS-CoV-2 vaccine; patients treated during the pandemic did not have a worse prognosis.

ANTECEDENTES: Durante la pandemia de COVID-19 se ha reportado incremento de casos de síndrome de Guillain-Barré (SGB). OBJETIVO: Describir características clínicas y pronóstico de pacientes con SGB antes y durante la pandemia de COVID-19. MATERIAL Y MÉTODOS: Cohorte prospectiva de pacientes con SGB estratificados en dos subgrupos: antes (2018-2019) y durante (2020-2021) la pandemia de COVID-19. Se registraron características clínicas, paraclínicas y defunciones. Se definió como buen pronóstico a la recuperación de la marcha independiente a los tres meses. RESULTADOS: Se incluyeron 201 pacientes (123 durante la pandemia y 78 antes), 69 % del sexo masculino, edad de 45 ± 16 años, 2.5 % de muertes intrahospitalarias. Durante la pandemia se observó mayor frecuencia de la variante desmielinizante (50 %), afección de nervios craneales bulbares (44 % versus 28 %), antecedente de vacunación (16 % versus 0 %) y menor puntuación en la escala MRC (30 ± 16.7 versus 34.3 ± 17.7); se observó aumento de casos de julio a septiembre (38 versus 13). No existieron diferencias significativas en la recuperación de la marcha independiente y número de defunciones. CONCLUSIONES: Durante la pandemia se atendió mayor número de casos de SGB, 16 % asociado a la vacuna contra SARS-CoV-2; los pacientes no presentaron peor pronóstico.

Particulate matter impairs immune system function by up-regulating inflammatory pathways and decreasing pathogen response gene expression.

Airborne particulate matter produced by industrial sources and automobiles has been linked to increased susceptibility to infectious diseases and it is known to be recognized by cells of the immune system. The molecular mechanisms and changes in gene expression profiles induced in immune cells by PM have not been fully mapped out or systematically integrated. Here, we use RNA-seq to analyze mRNA profiles of human peripheral blood mononuclear cells after exposure to coarse particulate matter (PM10). Our analyses showed that PM10 was able to reprogram the expression of 1,196 genes in immune cells, including activation of a proinflammatory state with an increase in cytokines and chemokines. Activation of the IL-36 signaling pathway and upregulation of chemokines involved in neutrophil and monocyte recruitment suggest mechanisms for inflammation upon PM exposure, while NK cell-recruiting chemokines are repressed. PM exposure also increases transcription factors associated with inflammatory pathways (e.g., JUN, RELB, NFKB2, etc.) and reduces expression of RNases and pathogen response genes CAMP, DEFAs, AZU1, APOBEC3A and LYZ. Our analysis across gene regulatory and signaling pathways suggests that PM plays a role in the dysregulation of immune cell functions, relevant for antiviral responses and general host defense against pathogens.

Síndrome de Guillain-Barré antes y durante la pandemia de COVID-19 en un centro de referencia de México / Guillain-Barre syndrome before and during the COVID-19 pandemic in a referral center of Mexico

Resumen Antecedentes: Durante la pandemia de COVID-19 se ha reportado incremento de casos de síndrome de Guillain-Barré (SGB). Objetivo: Describir características clínicas y pronóstico de pacientes con SGB antes y durante la pandemia de COVID-19. Material y métodos: Cohorte prospectiva de pacientes con SGB estratificados en dos subgrupos: antes (2018-2019) y durante (2020-2021) la pandemia de COVID-19. Se registraron características clínicas, paraclínicas y defunciones. Se definió como buen pronóstico a la recuperación de la marcha independiente a los tres meses. Resultados: Se incluyeron 201 pacientes (123 durante la pandemia y 78 antes), 69 % del sexo masculino, edad de 45 ± 16 años, 2.5 % de muertes intrahospitalarias. Durante la pandemia se observó mayor frecuencia de la variante desmielinizante (50 %), afección de nervios craneales bulbares (44 % versus 28 %), antecedente de vacunación (16 % versus 0 %) y menor puntuación en la escala MRC (30 ± 16.7 versus 34.3 ± 17.7); se observó aumento de casos de julio a septiembre (38 versus 13). No existieron diferencias significativas en la recuperación de la marcha independiente y número de defunciones. Conclusiones: Durante la pandemia se atendió mayor número de casos de SGB, 16 % asociado a la vacuna contra SARS-CoV-2; los pacientes no presentaron peor pronóstico.

Abstract Background: During the COVID-19 pandemic, an increase in the number of Guillain-Barre syndrome (GBS) cases has been reported. Objective: To describe the clinical characteristics and prognosis of patients with GBS before and during the COVID-19 pandemic. Material and methods: Prospective cohort of GBS patients divided in two subgroups: before (2018-2019) and during (2020-2021) the COVID-19 pandemic. Clinical and paraclinical characteristics, as well as deaths, were recorded. A good prognosis was defined as independent ambulation recovery at three months. Results: Two-hundred and one patients were included (123 during and 78 before the pandemic), out of whom 69 % were males; age was 45 ± 16 years, and there was 2.5 % of in-hospital deaths. During the pandemic, a higher frequency of the demyelinating variant (50 %), bulbar cranial nerves involvement (44 % vs. 28 %), prior history of vaccination (16 % vs. 0 %), and a lower MRC score (30 ± 16.7 vs. 34.3 ± 17.7) were documented. An increase in the number of cases was observed from July to September (38 vs. 13). There were no significant differences in independent ambulation recovery or in the number of deaths. Conclusions: During the COVID-19 pandemic, a higher number of GBS cases were treated, out of which 16 % were associated with the SARS-CoV-2 vaccine; patients treated during the pandemic did not have a worse prognosis.

Discrimination and Depressive Symptoms Among Mexican American Women: Exploring Multilevel Sociocultural Moderators.

Relative to empirical studies on risk factors, less research has focused on culturally based protective factors that reduce the impact of discrimination on mental health. The current prospective study evaluated two potential moderators of the effect of discrimination on depressive symptoms among Mexican American women: individually held familism values and neighborhood cultural cohesion. Mexican-origin women in the United States (N = 322; mean age = 27.8 years; 86% born in Mexico) reported on frequency of discrimination, depressive symptoms, familism, and neighborhood cultural cohesion. Independent models evaluated familism and neighborhood cultural cohesion as moderators of the effect of discrimination on subsequent depressive symptoms. More frequent discrimination predicted higher subsequent depressive symptoms. High familism buffered the harmful effect of discrimination on depressive symptoms, such that more frequent discrimination was associated with higher subsequent depressive symptoms only for women who reported average and low familism. Neighborhood cultural cohesion did not buffer the effect of discrimination on depressive symptoms.

PM10 promotes an inflammatory cytokine response that may impact SARS-CoV-2 replication in vitro.

Introduction: In the last decades, a decrease in air quality has been observed, mainly associated with anthropogenic activities. Air pollutants, including particulate matter (PM), have been associated with adverse effects on human health, such as exacerbation of respiratory diseases and infections. High levels of PM in the air have recently been associated with increased morbidity and mortality of COVID-19 in some regions of the world. Objective: To evaluate the effect of coarse particulate matter (PM10) on the inflammatory response and viral replication triggered by SARS-CoV-2 using in vitro models. Methods: Peripheral blood mononuclear cells (PBMC) from healthy donors were treated with PM10 and subsequently exposed to SARS-CoV-2 (D614G strain, MOI 0.1). The production of pro-inflammatory cytokines and antiviral factors was quantified by qPCR and ELISA. In addition, using the A549 cell line, previously exposed to PM, the viral replication was evaluated by qPCR and plaque assay. Results: SARS-CoV-2 stimulation increased the production of pro-inflammatory cytokines in PBMC, such as IL-1ß, IL-6 and IL-8, but not antiviral factors. Likewise, PM10 induced significant production of IL-6 in PBMCs stimulated with SARS-CoV-2 and decreased the expression of OAS and PKR. Additionally, PM10 induces the release of IL-1ß in PBMC exposed to SARS-CoV-2 as well as in a co-culture of epithelial cells and PBMCs. Finally, increased viral replication of SARS-CoV-2 was shown in response to PM10. Conclusion: Exposure to coarse particulate matter increases the production of pro-inflammatory cytokines, such as IL-1ß and IL-6, and may alter the expression of antiviral factors, which are relevant for the immune response to SARS-CoV-2. These results suggest that pre-exposure to air particulate matter could have a modest role in the higher production of cytokines and viral replication during COVID-19, which eventually could contribute to severe clinical outcomes.

In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approach.

Background: Drug repurposing is a valuable strategy for rapidly developing drugs for treating COVID-19. This study aimed to evaluate the antiviral effect of six antiretrovirals against SARS-CoV-2 in vitro and in silico. Methods: The cytotoxicity of lamivudine, emtricitabine, tenofovir, abacavir, efavirenz and raltegravir on Vero E6 was evaluated by MTT assay. The antiviral activity of each of these compounds was evaluated via a pre-post treatment strategy. The reduction in the viral titer was assessed by plaque assay. In addition, the affinities of the antiretroviral interaction with viral targets RdRp (RNA-dependent RNA polymerase), ExoN-NSP10 (exoribonuclease and its cofactor, the non-structural protein 10) complex and 3CLpro (3-chymotrypsin-like cysteine protease) were evaluated by molecular docking. Results: Lamivudine exhibited antiviral activity against SARS-CoV-2 at 200 µM (58.3%) and 100 µM (66.7%), while emtricitabine showed anti-SARS-CoV-2 activity at 100 µM (59.6%), 50 µM (43.4%) and 25 µM (33.3%). Raltegravir inhibited SARS-CoV-2 at 25, 12.5 and 6.3 µM (43.3%, 39.9% and 38.2%, respectively). The interaction between the antiretrovirals and SARS-CoV-2 RdRp, ExoN-NSP10 and 3CLpro yielded favorable binding energies (from -4.9 kcal/mol to -7.7 kcal/mol) using bioinformatics methods. Conclusion: Lamivudine, emtricitabine and raltegravir showed in vitro antiviral effects against the D614G strain of SARS-CoV-2. Raltegravir was the compound with the greatest in vitro antiviral potential at low concentrations, and it showed the highest binding affinities with crucial SARS-CoV-2 proteins during the viral replication cycle. However, further studies on the therapeutic utility of raltegravir in patients with COVID-19 are required.