An Overview on Actual Knowledge About Immunohistochemical and Molecular Features of Vitality, Focusing on the Growing Evidence and Analysis to Distinguish Between Suicidal and Simulated Hanging

In forensic practice, the pathologist is often asked to determine whether a hanging was committed as suicide or as a simulated hanging (when a dead body is suspended after death). When exterior evidence of violence is absent and the crime scene investigation fails to identify useful proof, it is nearly impossible to tell whether the dead body was suspended or not. As a result, determining whether the ligature mark was created during life or not should rely on the research and demonstration of vital reactions on the ligature mark. The main purpose of this review article is to provide a summary of current knowledge about the histological and immunohistochemical characteristics of vitality in hanging. The authors also aim to identify the most significant vitality markers on ligature marks for further scientific validation and to propose a standardized diagnostic protocol for hanging. The study was conducted according to the Preferred Reporting Items for Systematic Review (PRISMA) Protocol. Relevant scientific papers were found from PubMed up to April 2021, using the following keywords: hanging AND skin AND vitality. Three main points were studied: ligature mark dehydration, immunological response to mechanical injury, and apoptosis induction as a result of the previous points. An increase in apoptosis is evident in the ligature mark (due to physical and chemical processes involved), as demonstrated by FLICE-inhibitory protein (FLIP) depletion. Immunohistochemical detection of Aquaporin 3 (AQP3) and increase in the concentration of different electrolytes rely solely on ligature mark dehydration. Also, microRNAs (MiRNAs) could become reliable forensic biomarkers for ligature mark vitality diagnosis in the near future. To ensure high reliability in court cases, forensic investigation in hanging should rely on modern and proven markers, even a mix of several markers.

The Significance of Toll-Like Receptors in the Neuroimmunologic Background of Alcohol Dependence

Toll-like receptors (TLR) are a group of protein belonging to the family of Pattern Recognition Receptors (PRR) which have the ability to distinguish between an organism's own antigens and foreign ones and to induce immunological response. TLR play a significant part in non-specific immunity but at the same time they are also a vital element linking non-specific response to the specific one. A growing number of data seems to indicate that the non-specific immunity mechanisms affect the development and sustenance of alcohol addiction. Alcohol damages the organism's cells not only directly but also through an increase inintestinal permeability which induces innate immune response of peripheral blood cells. The signaling pathway of Toll-like receptors located on the surface of brain immune cells intensifies the inflammatory reaction and, through modifying gene expression of proinflammatory factors, unnaturally supports it. This overly protracted “sterile inflammatory reaction” positively correlates with alcohol craving affecting also the functioning of the reward system structures and increasing the risk of relapse of alcoholism. Recurrent alcoholic binges sensitize the microglia and cause an escalation in inflammatory reaction which also leads to neurodegeneration. The induction of innate immunity signaling pathways exposes clinical symptoms of alcohol addiction such as increased impulsivity, loss of behavioral control, depressive-anxiety symptoms and cognitive dysfunctions. Traditional methods of treating alcohol addiction have tended to focus predominantly on reducing symptoms which—given the frequency of relapses—seems insufficient. The aim of the present paper is to discuss the role of toll-like receptors as elements of the immunity system which, together with the nervous system, plays a crucial part in the pathogenesis of alcohol addiction. We also wish to present pharmacotherapeutic perspectives targeted at the neuroimmunological mechanisms of alcohol addiction.

Epithelial Barrier: Protector and Trigger of Allergic Disorders

The epithelial barrier has been classically considered as only the first line of defense against irritants, pathogens, and allergens, but it is now known that it also plays an essential role in the immunological response against exogenous agents. In fact, recent reports postulate the epithelial barrier hypothesis as a possible explanation for the increasing incidence and severity of allergic diseases. The epithelial barrier preserves the isolation of the inner tissues from potential external threats. Moreover, a coordinated interaction between epithelial and immune cells ensures the unique immune response taking place in mucosal tissues and that is has been reported to be dysregulated in allergic diseases. Herein, we and others have demonstrated that in severe allergic phenotypes, the epithelial barrier experiments several histological modifications and increased in immune cells infiltration, leading to its dysfunction. This is common in atopic dermatitis, asthma, and/or food allergy. However, the precise role of the epithelial barrier in the mucosal biology during allergic diseases progression is not well understood yet. In this review, we aim to compile recent knowledge regarding the histological structure and immunological function of the epithelial barrier and to shed light on the role of this compartment in the onset, and progression of allergic diseases.

Cutaneous ulceration as a presenting feature of type 1 lepra reaction: A case report

Reactions in leprosy represent sudden shift in the immunological response and are seen in 11–25% of affected patients. It can be seen before, during or after the completion of multidrug therapy (MDT). 1 Two types of reactions are recognized; Type 1 reaction (T1R), seen in borderline leprosy, affecting mainly skin and nerves; type 2 reaction (T2R) or erythema nodosum leprosum (ENL), seen in lepromatous leprosy, characterized by systemic features in addition to cutaneous lesions. Trophic ulcers and ulcerating ENL are well known entities while cutaneous ulceration in T1R is extremely rare; we describe an immune-competent woman with cutaneous ulceration as a presenting feature to highlight the need to recognize this entity at the earliest opportunity.

Systematic identification of NF90 target RNAs by iCLIP analysis

RNA-binding proteins (RBPs) interact with and determine the fate of many cellular RNAs directing numerous essential roles in cellular physiology. Nuclear Factor 90 (NF90) is an RBP encoded by the interleukin enhancer-binding factor 3 (ILF3) gene that has been found to influence RNA metabolism at several levels, including pre-RNA splicing, mRNA turnover, and translation. To systematically identify the RNAs that interact with NF90, we carried out iCLIP (individual-nucleotide resolution UV crosslinking and immunoprecipitation) analysis in the human embryonic fibroblast cell line HEK-293. Interestingly, many of the identified RNAs encoded proteins involved in the response to viral infection and RNA metabolism. We validated a subset of targets and investigated the impact of NF90 on their expression levels. Two of the top targets, IRF3 and IRF9 mRNAs, encode the proteins IRF3 and IRF9, crucial regulators of the interferon pathway involved in the SARS-CoV-2 immune response. Our results support a role for NF90 in modulating key genes implicated in the immune response and offer insight into the immunological response to the SARS-CoV-2 infection.

Epidemiology, etiology, and treatment of denture stomatitis

Multiple factors are involved in the pathogenesis of denture stomatitis, which increases the risk of tissue infection and inflammation. These factors include poor oral hygiene, trauma secondary to poorly fitting prostheses, resin porosity, and bacterial plaque accumulation. Our present review discusses the epidemiology, etiology, and treatment of denture stomatitis based on data from current studies in the literature. The prevalence of denture stomatitis is significantly variable among the different studies, as previously discussed. However, the cumulative incidence of denture stomatitis among their participants ranged between 17-77%. These hugely variable rates have been attributed to the nature of data collection, diagnostic criteria, sample size, and patient demographics. Studies also show that the condition is more prevalent among elderly females. However, not many studies have reported this correlation, indicating the need for future studies. Candida albicans infection is the primary parameter in the etiology and pathogenesis of the condition. However, other factors related to the patient (like status of immunological response) and dentures (like hygiene) were also reported. Therefore, the management of denture stomatitis should be based on applying adequate interventions. Besides, using antifungal medications is also necessary to eradicate organism.

The role of probiotics in the immune response and intestinal microbiota of children with celiac disease: a systematic review

ABSTRACT Objective: To evaluate changes in peripheral immunological response (decrease in blood proinflammatory cytokines) and fecal microbiota (especially Bacteroidetes and Firmicutes) after administration of probiotics in children with celiac disease on a gluten-free diet. Data source: The databases MEDLINE, LILACS, Springer and SciELO were used for this review, with the descriptors “celiac disease AND probiotics”. At the end of the search, 168 articles were retrieved, four of which were included in the final qualitative synthesis, having as inclusion criteria randomized clinical trials and pediatric population (1–19 years) and, as exclusion criteria, interventions other than probiotics, studies with patients with other diseases associated with celiac disease, or patients who did not meet the diagnostic criteria. All elected studies were published until September 2020, without language restriction, with patients receiving strains of Bifidobacterium breve or B. longum and on a gluten-free diet. Data synthesis: The studies show that the administration of probiotics along with a gluten-free diet, can approximate the fecal microbiota of celiac patients to typical conditions of healthy individuals, by restoring the abundance of some microbial communities that characterize the typical physiological condition. In addition, the administration of probiotics can reduce serum proinflammatory cytokines (mainly TNF-alpha). Conclusions: Despite the positive correlation between probiotics and fecal microbiota/serological markers in pediatric patients with celiac disease, we emphasize the need for future multicentric studies that should include a larger number of patients and a longer follow up period.%

A Real-World Evidence-Based Management of HIV by Differential Duration HAART Treatment and its Association with Incidence of Oral Lesions

Background: The efficacy of highly active antiretroviral therapy (HAART) therapy can be estimated by immunological response and the incidence of opportunistic infections. Objective: To evaluate the effectiveness of different durations of HAART in terms of immunological response markers (CD4 count and CD4/CD8 ratio) along with disease progression markers (incidence of oral lesions) in Chinese patients with HIV. Methods: This single-center, retrospective, real-world study included patients with HIV, grouped into treatment group and treatment-naïve group of which the former was further divided into (6, 12, and 18 months) based on the treatment duration. The CD4 and CD8 cell counts were analyzed by the FACSCalibur flow cytometry. Kruskal-Wallis test was applied to determine the outcome of different duration of HAART. Oral examination was carried out according to the WHO type IV examination Results: In 246 patients with HIV, CD4 counts increased significantly post-HAART compared with pre-HAART in all three treatment groups (P<.001), while CD8 count decreased significantly (P<.05) in all three treated group. A significant association of HAART with CD4/CD8 ratio was observed (P<.001). A significant increase in CD4 count was observed between 12-month and 18-month treatment group (P<.05). The occurrence of oral lesions reduced significantly in the treatment group. Conclusion: We observed a better response of HAART regimen with 18 months of duration than 12-months and 6-months therapies and reduction in oral lesions.