Evidence for predilection of macrophage infiltration patterns in the deeper midline and mesial temporal structures of the brain uniquely in patients with HIV-associated dementia

<p>Abstract</p> <p>Background</p> <p>HIV-1 penetrates the central nervous system, which is vital for HIV-associated dementia (HAD). But the role of cellular infiltration and activation together with HIV in the development of HAD is poorly understood.</p> <p>Methods</p> <p>To study activation and infiltration patterns of macrophages, CD8+ T cells in relation to HIV in diverse CNS areas of patients with and without dementia. 46 brain regions from two rapidly progressing severely demented patients and 53 regions from 4 HIV+ non-dementia patients were analyzed. Macrophage and CD8+ T cell infiltration of the CNS in relation to HIV was assessed using immuno-histochemical analysis with anti-HIV (P24), anti-CD8 and anti-CD68, anti-S-100A8 and granzyme B antibodies (cellular activation). Statistical analysis was performed with SPSS 12.0 with Student's t test and ANOVA.</p> <p>Results</p> <p>Overall, the patterns of infiltration of macrophages and CD8+ T cells were indiscernible between patients with and without dementia, but the co-localization of macrophages and CD8+ T cells along with HIV P24 antigen in the deeper midline and mesial temporal structures of the brain segregated the two groups. This predilection of infected macrophages and CD8+ T cells to the middle part of the brain was unique to both HAD patients, along with unique nature of provirus gag gene sequences derived from macrophages in the midline and mesial temporal structures.</p> <p>Conclusion</p> <p>Strong predilection of infected macrophages and CD8+ T cells was typical of the deeper midline and mesial temporal structures uniquely in HAD patients, which has some influence on neurocognitive impairment during HIV infection.</p

Nutrition and IBD: Malnutrition and/or Sarcopenia? A Practical Guide

Malnutrition is a major complication of inflammatory bowel disease (IBD). This mini review is focusing on main determinants of malnutrition in IBD, the most important components of malnutrition, including lean mass loss and sarcopenia, as an emerging problem. Each one of these components needs to be well considered in a correct nutritional evaluation of an IBD patient in order to build a correct multidisciplinary approach. The review is then focusing on possible instrumental and clinical armamentarium for the nutritional evaluation

Social cognition in people with schizophrenia: A cluster-analytic approach

Background The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. Method A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. Results We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. Conclusions If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person

MicroRNAs as Innovative Biomarkers for Inflammatory Bowel Disease and Prediction of Colorectal Cancer

Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn&rsquo;s disease (CD). These are autoimmune diseases of the gastrointestinal tract with a chronic relapsing and remitting course. Due to complex interactions between multiple factors in the etiology of IBD, the discovery of new predictors of disease course and response to therapy, and the development of effective therapies is a significant challenge. The dysregulation of microRNAs (miRNAs), a class of conserved endogenous, small non-coding RNA molecules with a length of 18&ndash;25 nucleotides, that regulate gene expression by an RNA interference process, is implicated in the complex pathogenetic context of IBD. Both tissue-derived, circulating, and fecal microRNAs have been explored as promising biomarkers in the diagnosis and the prognosis of disease severity of IBD. In this review, we summarize the expressed miRNA profile in blood, mucosal tissue, and stool and highlight the role of miRNAs as biomarkers with potential diagnostic and therapeutic applications in ulcerative colitis and Crohn&rsquo;s disease. Moreover, we discuss the new perspectives in developing a new screening model for the detection of colorectal cancer (CRC) based on fecal miRNAs

Solid Pahse Microextraction (SPME) Analysis of six Italian Populations of Ephedra nebrodensis Tineo subsb nebrodensis

Headspace solid-phase microextraction (HS-SPME) coupled with GC/FID and GC/MS was applied for the first time in the analysis of the volatile fraction of an Ephedra species. Notably, six Italian populations (Marche, Abruzzo, and Sardinia) of Ephedra nebrodensis subsp. nebrodensis, covering almost the entire Italian area, were investigated to examine the chemical variability and to support the taxonomy of the species. A fiber screening with polymethylsiloxane (PDMS), CarboxenTM/polymethylsiloxane (CAR/PDMS), and polymethylsiloxane/divinylbenzene (PDMS/DVB) coatings, together with an optimization of the extraction conditions were carried out before analysis of the six populations. A total of 119 volatiles were identified in the headspace of different samples, accounting for 63.35–100.00% of the total volatiles. A great variability was found in the qualitative composition of different samples, since only 18 components were in common among all populations. The headspace composition was dominated by sesquiterpene hydrocarbons (52.30–88.32%), with β-maaliene (traces–7.49%), β-patchoulene (traces–1.29%), β-panasinsene (traces–6.85%), α-isocomene (traces–31.25%), α-trans-bergamotene (traces–6.95%), alloaromadendrene (traces–33.20%), α-acoradiene (traces–9.41%), and γ-muurolene (0.61–16.33%) being the most abundant constituents. Noteworthy is the occurrence in a sample of two major unknown sesquiterpenes, one hydrocarbon (24.49%, RI: 1396) and one oxygenated compound (10.37%, RI: 1591), whose mass spectra were reported for the first time. Multivariate chemometric techniques, such as cluster analysis (CA) and principal component analysis (PCA), were used to characterize the samples according to the geographical origin

Commensal Clostridia: leading players in the maintenance of gut homeostasis

The gastrointestinal tract is a complex and dynamic network where an intricate and mutualistic symbiosis modulates the relationship between the host and the microbiota in order to establish and ensure gut homeostasis. Commensal Clostridia consist of gram-positive, rod-shaped bacteria in the phylum Firmicutes and make up a substantial part of the total bacteria in the gut microbiota. They start to colonize the intestine of breastfed infants during the first month of life and populate a specific region in the intestinal mucosa in close relationship with intestinal cells. This position allows them to participate as crucial factors in modulating physiologic, metabolic and immune processes in the gut during the entire lifespan, by interacting with the other resident microbe populations, but also by providing specific and essential functions. This review focus on what is currently known regarding the role of commensal Clostridia in the maintenance of overall gut function, as well as touch on their potential contribution in the unfavorable alteration of microbiota composition (dysbiosis) that has been implicated in several gastrointestinal disorders. Commensal Clostridia are strongly involved in the maintenance of overall gut function. This leads to important translational implications in regard to the prevention and treatment of dysbiosis, to drug efficacy and toxicity, and to the development of therapies that may modulate the composition of the microflora, capitalizing on the key role of commensal Clostridia, with the end goal of promoting gut health

Cellular and Molecular Determinants of Biologic Drugs Resistance and Therapeutic Failure in Inflammatory Bowel Disease

The advent of biologic drugs has revolutionized the treatment of Inflammatory Bowel Disease, increasing rates of response and mucosal healing in comparison to conventional therapies by allowing the treatment of corticosteroid-refractory cases and reducing corticosteroid-related side effects. However, biologic therapies (anti-TNFα inhibitors, anti-α4β7 integrin and anti-IL12/23) are still burdened by rates of response that hover around 40% (in biologic-naïve patients) or lower (for biologic-experienced patients). Moreover, knowledge of the mechanisms underlying drug resistance or loss of response is still scarce. Several cellular and molecular determinants are implied in therapeutic failure; genetic predispositions, in the form of single nucleotide polymorphisms in the sequence of cytokines or Human Leukocyte Antigen, or an altered expression of cytokines and other molecules involved in the inflammation cascade, play the most important role. Accessory mechanisms include gut microbiota dysregulation. In this narrative review of the current and most recent literature, we shed light on the mentioned determinants of therapeutic failure in order to pave the way for a more personalized approach that could help avoid unnecessary treatments and toxicities

Extrachromosomal Circular DNA: An Emerging Potential Biomarker for Inflammatory Bowel Diseases?

Inflammatory bowel disease (IBD) comprising ulcerative colitis and Crohn's disease is a chronic immune-mediated disease which affects the gastrointestinal tract with a relapsing and remitting course, causing lifelong morbidity. IBD pathogenesis is determined by multiple factors including genetics, immune and microbial factors, and environmental factors. Although therapy options are expanding, remission rates are unsatisfiable, and together with the disease course, response to therapy remains unpredictable. Therefore, the identification of biomarkers that are predictive for the disease course and response to therapy is a significant challenge. Extrachromosomal circular DNA (eccDNA) fragments exist in all tissue tested so far. These fragments, ranging in length from a few hundreds of base pairs to mega base pairs, have recently gained more interest due to technological advances. Until now, eccDNA has mainly been studied in relation to cancer due to its ability to act as an amplification site for oncogenes and drug resistance genes. However, eccDNA could also play an important role in inflammation, expressed both locally in the- involved tissue and at distant sites. Here, we review the current evidence on the molecular mechanisms of eccDNA and its role in inflammation and IBD. Additionally, the potential of eccDNA as a tissue or plasma marker for disease severity and/or response to therapy is evaluated

The Innate and Adaptive Immune System as Targets for Biologic Therapies in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is an immune-mediated inflammatory condition causing inflammation of gastrointestinal and systemic cells, with an increasing prevalence worldwide. Many factors are known to trigger and maintain inflammation in IBD including the innate and adaptive immune systems, genetics, the gastrointestinal microbiome and several environmental factors. Our knowledge of the involvement of the immune system in the pathophysiology of IBD has advanced rapidly over the last two decades, leading to the development of several immune-targeted treatments with a biological source, known as biologic agents. The initial focus of these agents was directed against the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) leading to dramatic changes in the disease course for a proportion of patients with IBD. However, more recently, it has been shown that a significant proportion of patients do not respond to anti-TNF-α directed therapies, leading a shift to other inflammatory pathways and targets, including those of both the innate and adaptive immune systems, and targets linking both systems including anti-leukocyte trafficking agents-integrins and adhesion molecules. This review briefly describes the molecular basis of immune based gastrointestinal inflammation in IBD, and then describes how several current and future biologic agents work to manipulate these pathways, and their clinical success to date

Dietary Magnesium Alleviates Experimental Murine Colitis through Modulation of Gut Microbiota

Nutritional deficiencies are common in inflammatory bowel diseases (IBD). In patients, magnesium (Mg) deficiency is associated with disease severity, while in murine models, dietary Mg supplementation contributes to restoring mucosal function. Since Mg availability modulates key bacterial functions, including growth and virulence, we investigated whether the beneficial effects of Mg supplementation during colitis might be mediated by gut microbiota. The effects of dietary Mg modulation were assessed in a murine model of dextran sodium sulfate (DSS)-induced colitis by monitoring magnesemia, weight, and fecal consistency. Gut microbiota were analyzed by 16S-rRNA based profiling on fecal samples. Mg supplementation improved microbiota richness in colitic mice, increased abundance of Bifidobacterium and reduced Enterobacteriaceae. KEEG pathway analysis predicted an increase in biosynthetic metabolism, DNA repair and translation pathways during Mg supplementation and in the presence of colitis, while low Mg conditions favored catabolic processes. Thus, dietary Mg supplementation increases bacteria involved in intestinal health and metabolic homeostasis, and reduces bacteria involved in inflammation and associated with human diseases, such as IBD. These findings suggest that Mg supplementation may be a safe and cost-effective strategy to ameliorate disease symptoms and restore a beneficial intestinal flora in IBD patients