Effect of multi-level social risk factors on developmental trajectories of sexual risk behaviors among Bahamian middle-to-late adolescents.

Background: Few studies have examined how multi-level social factors interact and affect developmental patterns of sexual risk among middle-to-late adolescents who are at risk of experiencing sexual risk behaviors. We examined developmental trajectories of sexual risk behaviors of boys and girls in middle-to-late adolescence and the effects of exposure to three social risk factors (poor parental monitoring, peer risk, and neighborhood risk).

Methods: We followed 2,332 Bahamian adolescents every six months from Grades 10-12.

Deciphering the role of protein kinase A in the control of FoxP3 expression in regulatory T cells in health and autoimmunity.

The molecular mechanisms that govern differential T cell development from CD4CD25conventional T (Tconv) into CD4CD25 forkhead-box-P3 (FoxP3) inducible regulatory T (iTreg) cells remain unclear. Herein, we investigated the relative contribution of protein kinase A (PKA) in this process. Mechanistically, we found that PKA controlled the efficiency of human iTreg cell generation through the expression of different FoxP3 splicing variants containing or not the exon 2.

A scoping review on innovative methods for personality observation.

Background: Personality's investigation has always been characterized as a central area of research for psychology, such that it was established in the 1920s as an autonomous scientific-disciplinary field. Identifying and observing the people's typical ways of "being in the world" has made possible to define the predictability of a pattern of behavioral responses related both to the possession of distinct characteristics of the agent subject and to specific environmental situations. In the actual scientific landscape, there is a strand of research that makes a description of personality through methodologies and indicators not usually used by psychology, but scientifically validated through standardized procedures.

Humoral efficacy of the third SARS-CoV-2 vaccine dose in Multiple Sclerosis subjects undergoing different disease-modifying therapies.

Background: It remains unclear how vaccine doses and combinations of vaccination and infection affect the magnitude and quality of immune responses, particularly against novel SARS-CoV-2 variants in subjects with immune-related disorders, such as people with multiple sclerosis (pwMS). Several studies have evaluated the duration of anti-SARS-CoV-2 immune protection in healthy individuals; however clinical data suggest an attenuated short-term humoral response to SARS-CoV-2 vaccines in pwMS receiving disease-modifying therapies (DMTs).

Methods: In this prospective study, we evaluated the humoral response to the third (3rd) BNT162b2 vaccine (booster) dose in a monocentric cohort of pwMS undergoing eight different DMTs, all without previous SARS-CoV-2 infection.

Epigenetics: An opportunity to shape innate and adaptive immune responses.

Epigenetics connects genetic and environmental factors: it includes DNA methylation, histone post-translational modifications and the regulation of chromatin accessibility by non-coding RNAs, all of which control constitutive or inducible gene transcription. This plays a key role in harnessing the transcriptional programs of both innate and adaptive immune cells due to its plasticity and environmental-driven nature, piloting myeloid and lymphoid cell fate decisions with no change in their genomic sequence. In particular, epigenetic marks at the site of lineage-specific transcription factors and maintenance of cell type-specific epigenetic modifications, referred to as 'epigenetic memory', dictate cell differentiation, cytokine production and functional capacity following repeated antigenic exposure in memory T cells.

Epigenetic Reprogramming of the Inflammatory Response in Obesity and Type 2 Diabetes.

For the past several decades, the prevalence of obesity and type 2 diabetes (T2D) has continued to rise on a global level. The risk contributing to this pandemic implicates both genetic and environmental factors, which are functionally integrated by epigenetic mechanisms. While these conditions are accompanied by major abnormalities in fuel metabolism, evidence indicates that altered immune cell functions also play an important role in shaping of obesity and T2D phenotypes.

Stromal and Immune Cell Dynamics in Tumor Associated Tertiary Lymphoid Structures and Anti-Tumor Immune Responses.

Tertiary lymphoid structures (TLS) are ectopic lymphoid organs that have been observed in chronic inflammatory conditions including cancer, where they are thought to exert a positive effect on prognosis. Both immune and non-immune cells participate in the genesis of TLS by establishing complex cross-talks requiring both soluble factors and cell-to-cell contact. Several immune cell types, including T follicular helper cells (Tfh), regulatory T cells (Tregs), and myeloid cells, may accumulate in TLS, possibly promoting or inhibiting their development.

Therapeutic opportunities to modulate immune tolerance through the metabolism-chromatin axis.

The ability of the immune system to discriminate external stimuli from self-components - namely immune tolerance - occurs through a coordinated cascade of events involving a dense network of immune cells. Among them, CD4CD25 T regulatory cells are crucial to balance immune homeostasis and function. Growing evidence supports the notion that energy metabolites can dictate T cell fate and function via epigenetic modifications, which affect gene expression without altering the DNA sequence.

Long term persistence of SARS-CoV-2 humoral response in multiple sclerosis subjects.

Background & Objectives: The persistence of the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 pandemic, partly due to the appearance of highly infectious variants, has made booster vaccinations necessary for vulnerable groups. Here, we present data regarding the decline of the SARS-CoV-2 BNT162b2 mRNA vaccine-induced humoral immune response in a monocentric cohort of MS patients.

Methods: 96 MS patients undergoing eight different DMTs, all without previous SARS-CoV-2 infection, were evaluated for anti-Spike IgG levels, 21 days (T1) and 5-6 months (T2) after the second SARS-CoV-2 BNT162b2 mRNA vaccine dose.

Interferon Beta-1a treatment promotes SARS-CoV-2 mRNA vaccine response in multiple sclerosis subjects.

Background: Several concerns exist on the immunogenicity of SARS-CoV-2 vaccines in multiple sclerosis (MS) subjects due to their immunomodulating disease modifying therapies (DMTs). Here we report a comparison of the humoral response to BNT162b2-mRNA coronavirus (COVID)-19 vaccine and the immunological phenotype in a cohort of 125 MS subjects undergoing different DMTs, with no history of SARS-CoV-2 infection.

Methods: We collected serum and blood samples at the first day of vaccine (T0) and 21 days after the second vaccine dose (T1) from 125 MS subjects, undergoing eight different DMTs.

CD4 T-Cell Activation Prompts Suppressive Function by Extracellular Vesicle-Associated MicroRNAs.

MicroRNAs (miRNAs), small non-coding molecules targeting messenger RNAs and inhibiting protein translation, modulate key biological processes, including cell growth and development, energy utilization, and homeostasis. In particular, miRNAs control the differentiation, survival, and activation of CD4 T conventional (Tconv) cells, key players of the adaptive immunity, and regulate the physiological response to infections and the pathological loss of immune homeostasis in autoimmunity. Upon T-cell receptor (TCR) stimulation, the described global miRNA quantitative decrease occurring in T cells is believed to promote the acquisition of effector functions by relaxing the post-transcriptional repression of genes associated with proliferation and cell activity.

Serosurvey of antibodies against zoonotic pathogens in free-ranging wild canids (Cerdocyon thous and Lycalopex gymnocercus) from Southern Brazil.

The expansion of urbanization on natural areas is increasing contact between human populations with wild animals. Wild carnivores can act as sentinel hosts or environmental health indicators. Thus, the aim of this work was to investigate the exposure of two major species of wild canids from Southern Brazil to selected pathogens.

Healthcare cost associations of patients who use illicit drugs in Florida: a retrospective analysis.

Background: Illicit drug use increases visits to the hospital. Research is limited on the costs of these healthcare visits by illicit drug.

Methods: Florida's Agency for Health Care Administration's emergency department and inpatient datasets from 2016 to 2018 were analyzed.

The DEL-1/β3 integrin axis promotes regulatory T cell responses during inflammation resolution.

FOXP3+CD4+ regulatory T cells (Tregs) are critical for immune homeostasis and respond to local tissue cues, which control their stability and function. We explored here whether developmental endothelial locus-1 (DEL-1), which, like Tregs, increases during resolution of inflammation, promotes Treg responses. DEL-1 enhanced Treg numbers and function at barrier sites (oral and lung mucosa).

T1D progression is associated with loss of CD3CD56 regulatory T cells that control CD8 T cell effector functions.

An unresolved issue in autoimmunity is the lack of surrogate biomarkers of immunological self-tolerance for disease monitoring. Here, we show that peripheral frequency of a regulatory T cell population, characterized by the co-expression of CD3 and CD56 molecules (T), is reduced in subjects with new-onset type 1 diabetes (T1D). In three independent T1D cohorts, we find that low frequency of circulating T cells is associated with reduced β-cell function and with the presence of diabetic ketoacidosis.

Molecular Mechanisms Controlling Foxp3 Expression in Health and Autoimmunity: From Epigenetic to Post-translational Regulation.

The discovery of the transcription factor Forkhead box-p3 (Foxp3) has shed fundamental insights into the understanding of the molecular determinants leading to generation and maintenance of T regulatory (Treg) cells, a cell population with a key immunoregulatory role. Work over the past few years has shown that fine-tuned transcriptional and epigenetic events are required to ensure stable expression of Foxp3 in Treg cells. The equilibrium between phenotypic plasticity and stability of Treg cells is controlled at the molecular level by networks of transcription factors that bind regulatory sequences, such as enhancers and promoters, to regulate Foxp3 expression.

Metabolism and Autoimmune Responses: The microRNA Connection.

Distinct metabolic pathways are known to regulate growth, differentiation, survival, and activation of immune cells by providing energy and specific biosynthetic precursors. Compelling experimental evidence demonstrates that effector T cell functions are coupled with profound changes in cellular metabolism. Importantly, the effector T cell-dependent "anti-self" response characterizing the autoimmune diseases is accompanied by significant metabolic alterations.

Reduced Annexin A1 Expression Associates with Disease Severity and Inflammation in Multiple Sclerosis Patients.

Chronic neuroinflammation is a key pathological hallmark of multiple sclerosis (MS) that suggests that resolution of inflammation by specialized proresolving molecules is dysregulated in the disease. Annexin A1 (ANXA1) is a protein induced by glucocorticoids that facilitates resolution of inflammation through several mechanisms that include an inhibition of leukocyte recruitment and activation. In this study, we investigated the ability of ANXA1 to influence T cell effector function in relapsing/remitting MS (RRMS), an autoimmune disease sustained by proinflammatory Th1/Th17 cells.

Type 2 Diabetes: How Much of an Autoimmune Disease?

Type 2 diabetes (T2D) is characterized by a progressive status of chronic, low-grade inflammation (LGI) that accompanies the whole trajectory of the disease, from its inception to complication development. Accumulating evidence is disclosing a long list of possible "triggers" of inflammatory responses, many of which are promoted by unhealthy lifestyle choices and advanced age. Diabetic patients show an altered number and function of immune cells, of both innate and acquired immunity.

An immunometabolic pathomechanism for chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is an inflammatory condition associated with abnormal immune responses, leading to airflow obstruction. Lungs of COPD subjects show accumulation of proinflammatory T helper (Th) 1 and Th17 cells resembling that of autoreactive immune responses. As regulatory T (T) cells play a central role in the control of autoimmune responses and their generation and function are controlled by the adipocytokine leptin, we herein investigated the association among systemic leptin overproduction, reduced engagement of glycolysis in T cells, and reduced peripheral frequency of T cells in different COPD stages.

Obesity worsens central inflammation and disability in multiple sclerosis.

Background: Previous studies evidenced a link between metabolic dysregulation, inflammation, and neurodegeneration in multiple sclerosis (MS).

Objectives: To explore whether increased adipocyte mass expressed as body mass index (BMI) and increased serum lipids influence cerebrospinal fluid (CSF) inflammation and disease severity.

Methods: In this cross-sectional study, 140 consecutive relapsing-remitting (RR)-MS patients underwent clinical assessment, BMI evaluation, magnetic resonance imaging scan, and blood and CSF collection before any specific drug treatment.

The Multifaceted Interface Between Cytokines and microRNAs: An Ancient Mechanism to Regulate the Good and the Bad of Inflammation.

MicroRNAs (miRNAs) are evolutionary conserved small non-coding RNA molecules that affect gene expression by binding to target messenger RNAs and play a role in biological processes like cell growth, differentiation, and death. Different CD4 T cell subsets such as Th1, Th2, Th17, and T regulatory cells, exert a distinct role in effector and regulatory-type immune responses. miRNAs have been shown to respond to dynamic micro-environmental cues and regulate multiple functions of T cell subsets including their development, survival and activation.

FoxP3 isoforms and PD-1 expression by T regulatory cells in multiple sclerosis.

Forkhead box P3 (FoxP3)+ regulatory T cells (Treg) are powerful mediators of immune regulation and immune homeostasis. In humans, Tregs are a heterogeneous population expressing surface markers which define phenotypically and functionally distinct subsets. Moreover, it is now clear that intracellular staining for FoxP3 does not unequivocally identify "true" suppressor cells, since several FoxP3 isoforms exist, and different reagents for FoxP3 detection are available.