Substance use and treatment outcomes among Spanish-speaking Latino/as from four acculturation types.

The purpose of this study was to examine the association of acculturation with substance use treatment outcomes in a sample of treatment-seeking Latino/as (N = 405). The study used data from a multisite randomized controlled trial of a culturally adapted version of Motivational Enhancement Therapy delivered in Spanish. Berry, Kim, Minde, and Mok\u27s (1987) acculturation model was used to divide the sample into 4 types (integrated, assimilated, separated, marginalized), based on Bicultural Involvement Questionnaire scores. One-way analyses of variance, chi-squared tests, and repeated-measures regression were used to examine baseline acculturation, posttreatment outcomes, and follow-up outcomes. All participants were of Latino/a background, and 88.4% of the sample was male. Participants with greater acculturation to American culture (i.e., integrated and assimilated acculturation types) reported more substance use and associated problems at baseline, χ²(3) = 20.5, p \u3c .001, with the integrated type reporting the highest percentage of substance use disorder symptoms and problems (67.6%). No significant differences in substance use were detected among acculturation types posttreatment or at follow-up. Although the integrated and assimilated acculturation types were associated at baseline with more substance use and associated problems, all acculturation types seemed to benefit at posttreatment from an evidence-based culturally adapted treatment. (PsycINFO Database Recor

A Test of Multisession Automatic Action Tendency Retraining to Reduce Alcohol Consumption Among Young Adults in the Context of a Human Laboratory Paradigm.

BACKGROUND: Young adult heavy drinking is an important public health concern. Current interventions have efficacy but with only modest effects, and thus, novel interventions are needed. In prior studies, heavy drinkers, including young adults, have demonstrated stronger automatically triggered approach tendencies to alcohol-related stimuli than lighter drinkers. Automatic action tendency retraining has been developed to correct this tendency and consequently reduce alcohol consumption. This study is the first to test multiple iterations of automatic action tendency retraining, followed by laboratory alcohol self-administration. METHODS: A total of 72 nontreatment-seeking, heavy drinking young adults ages 21 to 25 were randomized to automatic action tendency retraining or a control condition (i.e., sham training ). Of these, 69 (54% male) completed 4 iterations of retraining or the control condition over 5 days with an alcohol drinking session on Day 5. Self-administration was conducted according to a human laboratory paradigm designed to model individual differences in impaired control (i.e., difficulty adhering to limits on alcohol consumption). RESULTS: Automatic action tendency retraining was not associated with greater reduction in alcohol approach tendency or less alcohol self-administration than the control condition. The laboratory paradigm was probably sufficiently sensitive to detect an effect of an experimental manipulation given the range of self-administration behavior observed, both in terms of number of alcoholic and nonalcoholic drinks and measures of drinking topography. CONCLUSIONS: Automatic action tendency retraining was ineffective among heavy drinking young adults without motivation to change their drinking. Details of the retraining procedure may have contributed to the lack of a significant effect. Despite null primary findings, the impaired control laboratory paradigm is a valid laboratory-based measure of young adult alcohol consumption that provides the opportunity to observe drinking topography and self-administration of nonalcoholic beverages (i.e., protective behavioral strategies directly related to alcohol use)

Epstein-Barr virus persistence and infection of autoreactive plasma cells in synovial lymphoid structures in rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is associated with an increased Epstein-Barr virus (EBV) blood DNA load, a robust immune response to EBV and cross-reactive circulating antibodies to viral and self-antigens. However, the role of EBV in RA pathogenesis remains elusive. Here, we investigated the relationship between synovial EBV infection, ectopic lymphoid structures (ELS) and immunity to citrullinated self and EBV proteins. METHODS: Latent and lytic EBV infection was investigated in 43 RA synovial tissues characterised for presence/absence of ELS and in 11 control osteoarthritis synovia using RT-PCR, in situ hybridisation and immunohistochemistry. Synovial production of anti-citrullinated protein (ACPA) and anti-citrullinated EBV peptide (VCP1/VCP2) antibodies was investigated in situ and in vivo in the severe combined immunodeficiency (SCID)/RA chimeric model. RESULTS: EBV dysregulation was observed exclusively in ELS+ RA but not osteoarthritis (OA) synovia, as revealed by presence of EBV latent (LMP2A, EBV-encoded small RNA (EBER)) transcripts, EBER+ cells and immunoreactivity for EBV latent (LMP1, LMP2A) and lytic (BFRF1) antigens in ELS-associated B cells and plasma cells, respectively. Importantly, a large proportion of ACPA-producing plasma cells surrounding synovial germinal centres were infected with EBV. Furthermore, ELS-containing RA synovia transplanted into SCID mice supported production of ACPA and anti-VCP1/VCP2 antibodies. Analysis of CD4+ and CD8+ T-cell localisation and granzyme B expression suggests that EBV persistence in ELS-containing synovia may be favoured by exclusion of CD8+ T cells from B-cell follicles and impaired CD8-mediated cytotoxicity. CONCLUSIONS: We demonstrated active EBV infection within ELS in the RA synovium in association with local differentiation of ACPA-reactive B cells

Roles of GM-CSF in the Pathogenesis of Autoimmune Diseases: An Update.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was first described as a growth factor that induces the differentiation and proliferation of myeloid progenitors in the bone marrow. GM-CSF also has an important cytokine effect in chronic inflammatory diseases by stimulating the activation and migration of myeloid cells to inflammation sites, promoting survival of target cells and stimulating the renewal of effector granulocytes and macrophages. Because of these pro-cellular effects, an imbalance in GM-CSF production/signaling may lead to harmful inflammatory conditions. In this context, GM-CSF has a pathogenic role in autoimmune diseases that are dependent on cellular immune responses such as multiple sclerosis (MS) and rheumatoid arthritis (RA). Conversely, a protective role has also been described in other autoimmune diseases where humoral responses are detrimental such as myasthenia gravis (MG), Hashimoto\u27s thyroiditis (HT), inflammatory bowel disease (IBD), and systemic lupus erythematosus (SLE). In this review, we aimed for a comprehensive analysis of literature data on the multiple roles of GM-CSF in autoimmue diseases and possible therapeutic strategies that target GM-CSF production

G9a regulates group 2 innate lymphoid cell development by repressing the group 3 innate lymphoid cell program.

Innate lymphoid cells (ILCs) are emerging as important regulators of homeostatic and disease-associated immune processes. Despite recent advances in defining the molecular pathways that control development and function of ILCs, the epigenetic mechanisms that regulate ILC biology are unknown. Here, we identify a role for the lysine methyltransferase G9a in regulating ILC2 development and function. Mice with a hematopoietic cell-specific deletion of G9a (Vav.G9a(-/-) mice) have a severe reduction in ILC2s in peripheral sites, associated with impaired development of immature ILC2s in the bone marrow. Accordingly, Vav.G9a(-/-) mice are resistant to the development of allergic lung inflammation. G9a-dependent dimethylation of histone 3 lysine 9 (H3K9me2) is a repressive histone mark that is associated with gene silencing. Genome-wide expression analysis demonstrated that the absence of G9a led to increased expression of ILC3-associated genes in developing ILC2 populations. Further, we found high levels of G9a-dependent H3K9me2 at ILC3-specific genetic loci, demonstrating that G9a-mediated repression of ILC3-associated genes is critical for the optimal development of ILC2s. Together, these results provide the first identification of an epigenetic regulatory mechanism in ILC development and function

Metabolism within the tumor microenvironment and its implication on cancer progression: an ongoing therapeutic target

Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment. Metabolic features of these cells are being studied in deep in order to find relationships between metabolism within the tumor microenvironment and tumor progression. Moreover, it cannot be forgotten that tumor growth is able to modulate host metabolism and homeostasis, so that tumor microenvironment is not the whole story. Importantly, the metabolic switch in cancer is just a consequence of the flexibility and adaptability of metabolism and should not be surprising. Treatments of cancer patients with combined therapies including anti-tumor agents with those targeting stromal cell metabolism, anti-angiogenic drugs and/or immunotherapy are being developed as promising therapeutics.Mª Carmen Ocaña is recipient of a predoctoral FPU grant from the Spanish Ministry of Education, Culture and Sport. Supported by grants BIO2014-56092-R (MINECO and FEDER), P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript

Chemical composition, antinociceptive, anti-inflammatory and redox properties in vitro of the essential oil from Remirea maritima Aubl. (Cyperaceae)

Methods: The essential oil from the roots and rhizomes of RMO were obtained by hydrodistillation using a Clevenger apparatus, and analyzed by gas chromatography/mass spectrometry (GC/MS). Here, we evaluated free radical scavenging activities and antioxidant potential of RMO using in vitro assays for scavenging activity against hydroxyl radicals, hydrogen peroxide, superoxide radicals, and nitric oxide. The total reactive antioxidant potential (TRAP) and total antioxidant reactivity (TAR) indexes and in vitro lipoperoxidation were also evaluated. The ability of RMO to prevent lipid peroxidation was measured by quantifying thiobarbituric acid-reactive substances (TBARS). NO radical generated at physiological pH was found to be inhibited by RMO, that showed scavenging effect upon SNP-induced NO production at all concentrations. Antinociceptive and anti-inflammatory properties were evaluated by acetic acid writhing reflex, Formalin-induced nociception and Carrageenan-induced edema test. - Results: The majors compounds identified was remirol (43.2%), cyperene (13.8%), iso-evodionol (5.8%), cyperotundone (5.7%), caryophyllene oxide (4.9%), and rotundene (4.6%). At the TRAP assay, RMO concentration of 1 mg.mL−1 showed anti-oxidant effects and at concentration of 1 and 10 ng.mL−1 RMO showed pro-oxidant effect. RMO at 1 mg.mL−1 also showed significant anti-oxidant capacity in TAR measurement. Concentrations of RMO from 1 ng.mL−1 to 100 μg.mL−1 enhanced the AAPH-induced lipoperoxidation. RMO reduced deoxyribose oxidative damage, induced by the Fenton reaction induction system, at concentrations from 1 ng.mL−1 to 100 μg.mL−1. We observed that RMO caused a significant increase in rate of adrenaline auto-oxidation. On the other hand RMO did not present any scavenging effect in H2O2 formation in vitro. The results of this study revealed that RMO has both peripheral and central analgesic properties. The RMO, all doses, orally (p.o.) administered significantly inhibited (p < 0.05, p < 0.01 and p < 0.001) the acetic acid-induced writhings and two phases of formalin-induced nociception in mice. - Conclusion: The RMO demonstrated antioxidant and analgesic profile which may be related to the composition of the oil

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project

Purpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection