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Some patients with HIV develop dementia. Using in vivo proton nuclear magnetic resonance ((1)H-NMR) spectroscopy, it is possible to measure the metabolic changes noninvasively. In this study, it is of interest to answer the clinically relevant question of whether magnetic resonance spectroscopy is suitable for the diagnosis of HIV encephalopathy. In total, 14 HIV-positive patients were investigated by means of localized (1)H-NMR spectroscopy in the following locations: (1) the mid-parietal gray matter, (2) the parietal white matter (PWM), and (3) the frontal white matter. All patients had no other brain diseases, apart from the HIV encephalopathy. The clinical extent of HIV encephalopathy of each patient was investigated using the following tests: (1) an electroencephalogram, (2) a neurological examination and psychiatric assessment, and (3) a psychometrical test. The spectroscopic changes in the PWM were more pronounced than those in the cortex, and the myo-inositol/creatine (mI/Cr) signal showed a clear increase in the cortex. Overall, the mI/Cr ratio emerged as the most reliable and earliest parameter to indicate an HIV encephalopathy. [ABSTRACT FROM AUTHOR]

Background and Objective: Urinary tract infections (UTIs) are some of the most encountered infections in clinical practice, exhibiting increasing antimicrobial resistance. Bacterial species identification and antimicrobial resistance testing at point of care (POCT) could improve adequate initial antibiotic therapy and antimicrobial stewardship. In this work, the Vivalytic UTI test, which represents a qualitative PCR-based microarray test, able to detect specific uropathogenic bacteria and associated antimicrobial resistance genes was evaluated at POCT., Methods: In September 2023, we used this point-of-care testing (POCT) to analyse 126 consecutive urine samples of patients with complicated UTI. Samples processed with the Vivalytic UTI POCT were preselected for the presence of bacteriuria by screening with urine flow cytometry (cut-off ≥70 bacteria per microlitre). We performed the POCT before and after sample transport, and compared the results to standard urine culture and antibiotic sensitivity tests according to the European Committee on Antimicrobial Susceptibility Testing., Key Findings and Limitations: Nineteen different bacterial species were detected. Sixteen species reached a diagnostic accuracy of ≥90.27% with negative predictive values of ≥93.67%. The POCT was able to detect bacterial species under the estimated concentration of 10 4 -5 × 10 4  CFU/ml. The concordant (Vivalytic vs. culture) antimicrobial resistance gene detection rate reached a higher accuracy after transport (≥84.15%) compared to POC-testing before transport (≥81.71%), except for Vancomycin. Aerococcus urinae, Enterococcus hirae, Hafnia alvei, and Staphylococcus lugdunensis are not part of the POCT test panel; these were detected by urine culture only in 19% of cases., Conclusions and Clinical Implications: The Vivalytic UTI POCT displayed high sensitivity and specificity in identifying uropathogenic bacteria and antibiotic resistance markers to be further evaluated in clinical practice. However, it would be helpful to expand the resistance to include information about more commonly used antibiotics like aminopenicillins, cephalosporines and fluoroquinolones., Patient Summary: In this study, we tested 126 consecutive urine samples of urological patients with complicated urinary tract infections (UTIs) by using the Vivalytic UTI point-of-care testing before and after sample transport. We found out that the sample transport to some extent influences the pathogen and resistance detection rate of the Vivalytic UTI assay. Compared to standard-of-care diagnostics, pathogen identification was more accurate before sample transport, while the concordant antimicrobial resistance gene detection rate reached higher accuracy after transport., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Liver cancer represents a substantial global health challenge, contributing significantly to worldwide morbidity and mortality. It has long been understood that tumors are not composed solely of cancerous cells, but also include a variety of normal cells within their structure. These tumor-associated normal cells encompass vascular endothelial cells, fibroblasts, and various inflammatory cells, including neutrophils, monocytes, macrophages, mast cells, eosinophils, and lymphocytes. Additionally, tumor cells engage in complex interactions with stromal cells and elements of the extracellular matrix (ECM). Initially, the components of what is now known as the tumor microenvironment (TME) were thought to be passive bystanders in the processes of tumor proliferation and local invasion. However, recent research has significantly advanced our understanding of the TME's active role in tumor growth and metastasis. Tumor progression is now known to be driven by an intricate imbalance of positive and negative regulatory signals, primarily influenced by specific growth factors produced by both inflammatory and neoplastic cells. This review article explores the latest developments and future directions in understanding how the TME modulates liver cancer, with the aim of informing the design of novel therapies that target critical components of the TME.

Multiple sclerosis (MS) is a disease of the central nervous system (CNS) characterized by inflammation and autoimmune responses. This review explores the participation of T cells, particularly certain CD3 + CD20 + T cells, in the clinical manifestations of MS and highlights their presence in diagnosed patients. These T cells show aberrant expression of CD20, normally considered a B-cell marker. In this review, relevant journal articles available in PubMed and CINAHL were identified by employing diverse search terms, such as MS, CD3 + CD20 + T cells, the incidence and significance of CD3 + CD20 + T cells in MS patients, and the impact of rituximab treatment. The search was limited to articles published in the ten-year period from 2014 to 2024. The results of this review suggest that most scholars agree on the presence of CD3 + CD20 + T cells in cerebrospinal fluid. Emerging concepts relate to the fundamental role of CD20-expressing T cells in determining the target and efficacy of MS therapeutics and the presence of T cells in the cerebrospinal fluid of MS patients. The results clearly show that CD20 + T cells indicate disease chronicity and high disease activity.

Colorectal cancer (CRC) represents a significant global healthcare burden, with a particularly concerning rising incidence among younger adults. This trend may highlight potential links between diet, gut microbiome, and CRC risk. Novel therapeutic options have been increasingly based on the understanding of molecular mechanisms and pathways. The PI3K/AKT/mTOR pathway, a crucial cell growth regulator, offers a promising target for CRC therapy. mTOR, a key component within this pathway, controls cell growth, survival, and metabolism. Understanding the specific roles of defensins, particularly human β-Defensin 1 (HBD-1), in CRC is crucial. HBD-1 exhibits potent antimicrobial activity and may influence CRC development. Deciphering defensin expression patterns in CRC holds the promise of improved understanding of tumorigenesis, which may pave the way for improved diagnostics and therapies. This article reviews recent advances in understanding regarding how HBD-1 influences CRC initiation and progression, highlighting the molecular mechanisms by which it impacts CRC. Further, we describe the interaction between defensins and mTOR pathway in CRC.

Monocytes play a critical role in the initiation and progression of multiple sclerosis (MS). Recent research indicates the importance of considering the roles of monocytes in the management of MS and the development of effective interventions. This systematic review examined published research on the roles of nonclassical monocytes in MS and how they influence disease management. Reputable databases, such as PubMed, EMBASE, Cochrane, and Google Scholar, were searched for relevant studies on the influence of monocytes on MS. The search focused on studies on humans and patients with experimental autoimmune encephalomyelitis (EAE) published between 2014 and 2024 to provide insights into the study topic. Fourteen articles that examined the role of monocytes in MS were identified; the findings reported in these articles revealed that nonclassical monocytes could act as MS biomarkers, aid in the development of therapeutic interventions, reveal disease pathology, and improve approaches for monitoring disease progression. This review provides support for the consideration of monocytes when researching effective diagnostics, therapeutic interventions, and procedures for managing MS pathophysiology. These findings may guide future research aimed at gaining further insights into the role of monocytes in MS.

Background: Multiple sclerosis (MS) is an autoimmune disorder that affects the central nervous system (CNS) through inflammation. MS symptoms become acute if the disease progresses to the relapsing phase., Aim: This review aimed to evaluate the role played by regulatory T cells (Tregs) in the pathogenesis of MS., Methods: This review used scholarly journal articles obtained from PubMed, PsycINFO, and CINAHL with different search parameters such as 'regulatory T cells', 'multiple sclerosis', and 'current knowledge'. The process of searching for articles was limited to those that had publication dates falling between 2010 and 2020., Results: Tregs play a role in the pathogenesis of MS. This conclusion is supported by animal disease models and environmental factors that can underlie Treg alterations in MS. Despite the knowledge of the role played by Tregs in MS pathogenesis, the specific subsets of Tregs involved in MS development remain incompletely understood., Discussion: This review provides an essential link between Tregs and MS activity. Targeting Tregs could be an efficient way to establish new treatment methods for MS management., Conclusion: MS is a complex condition affecting many people worldwide. Research has shown that Tregs can influence MS development and progression. More investigations are needed to understand how Tregs affect the pathogenesis of MS.

Although various viruses are considered to be the clinical cause for acute orchitis, it is completely unclear to what extent and which viruses are etiologically involved in acute orchitis and what the clinic and course of these patients are like. Therefore, a prospective study was set up to decipher acute isolated orchitis. Between July 2007 and February 2023, a total of 26 patients with isolated orchitis were recruited and compared with 530 patients with acute epididymitis. We were able to show for isolated orchitis, that (1) orchitis is usually of viral origin (20/26, 77%) and enteroviruses with coxsackievirus B strains (16/26, 62%) are predominant, (2) virus isolates could be received from semen indicating the presence of replication-competent virus particles, (3) a polymerase chain reaction (PCR) for enteroviruses should be conducted using semen provided at the onset of disease, because the virus is not detectable in serum/urine, (4) there is a circannual occurrence with the maximum in summer, (5) orchitis is associated with a characteristic inflammatory cytokine panel in the semen and systemic inflammation, (6) orchitis is usually rapidly self-limiting, and (7) about 30% of patients (6/20) suffer ongoing oligozoospermia. These seven emerging aspects are likely to fundamentally change thinking and clinical practice regarding acute isolated orchitis., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system; the cause of this condition remains unknown. Researchers have analyzed different biomarkers related to MS. Here, experimental laboratory biomarkers for MS are identified and analyzed., Methods: The current study examined articles investigating biomarkers for MS. Records were obtained from the PubMed, LILACS, and EBSCO databases using an identical search strategy and terms that included "multiple sclerosis," "MS," and "biomarkers." In the current review, we also focus on lesser known biomarkers that have not yet been established for use in clinical practice., Results: Previous studies have explored molecular substances that may help diagnose MS and manage its adverse effects. Commonly studied factors include neurofilaments, sCD163, CXCL13, NEO, NF‑L, OPN, B cells, T cells, and integrin-binding proteins., Conclusions: Interactions between environmental and genetic factors have been implicated in the development of MS. Previous investigations have identified a wide range of biomarkers that can be used for diagnosis and disease management. These molecules and their associated studies provide vital insight and data to help primary physicians improve clinical and health outcomes for MS patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, ein Teil von Springer Nature.)

Background : The positive implications of using free light chains in diagnosing multiple sclerosis have increasingly gained considerable interest in medical research and the scientific community. It is often presumed that free light chains, particularly kappa and lambda free light chains, are of practical use and are associated with a higher probability of obtaining positive results compared to oligoclonal bands. The primary purpose of the current paper was to conduct a systematic review to assess the up-to-date methods for diagnosing multiple sclerosis using kappa and lambda free light chains. Method : An organized literature search was performed across four electronic sources, including Google Scholar, Web of Science, Embase, and MEDLINE. The sources analyzed in this systematic review and meta-analysis comprise randomized clinical trials, prospective cohort studies, retrospective studies, controlled clinical trials, and systematic reviews. Results : The review contains 116 reports that includes 1204 participants. The final selection includes a vast array of preexisting literature concerning the study topic: 35 randomized clinical trials, 21 prospective cohort studies, 19 retrospective studies, 22 controlled clinical trials, and 13 systematic reviews. Discussion : The incorporated literature sources provided integral insights into the benefits of free light chain diagnostics for multiple sclerosis. It was also evident that the use of free light chains in the diagnosis of clinically isolated syndrome (CIS) and multiple sclerosis is relatively fast and inexpensive in comparison to other conventional state-of-the-art diagnostic methods, e.g., using oligoclonal bands (OCBs).

Introduction: The aims of this study were to evaluate urine flow cytometry (UFC) as a tool to screen urine samples of urological patients for bacteriuria and to compare UFC and dipstick analysis with urine culture in a patient cohort at a urological department of a university hospital., Methods and Material: We screened 662 urine samples from urological patients (75.2% male; 80.7% inpatients; mean age 58 years). UFC results were compared to microbiological urine culture., Results: The accuracy in using the UFC-based parameters for detecting cultural bacteriuria was 91.99% and 88.97% for ≥105 colony-forming units (CFU)/mL and ≥104 CFU/mL, respectively. UFC and leukocyte dipstick analysis measured leukocyturia similarly (Pearson correlation coefficient 0.87, p value <0.01%), but dipstick analysis scored less accurately on bacteriuria (accuracy 59.37% and 62.69%). UFC remained effective in subgroup analysis of patients of both sexes and with different urological conditions with its overall use only slightly impaired when assessing gross hematuria (NPV 84.62% for ≥104 CFU/mL). UFC also reliably removed those urine samples below cutoffs with negative predictive values of 99.28% for ≥105 CFU/mL and 95.86% for ≥104 CFU/mL., Conclusion: Counting bacteria with UFC is an accurate and rapid method to determine significant bacteriuria in urological patients and is superior to dipstick analysis or indirect surrogate parameters such as leukocyturia. When UFC is available, we recommend it to be used for the diagnosis of bacteriuria over findings obtained by dipstick analysis., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Nucleotides and platelets have been associated with a wide range of activities that affect the host inflammatory response. The main goal of this study is to examine the roles of nucleotide signaling and platelets in inflammation. The study analysis entailed conducting a systematic search to identify relevant articles in PsycINFO, PubMed, Web of Science, and CINAHL. The evidence gathered from the identified articles shows the roles of nucleotides and platelets in inflammation. In the extracellular environment, nucleotides act as signaling molecules that can activate nucleotide receptors to promote inflammation. Inflammation is an essential process through which the innate immune system responds to pathogens, microbes, and damage-associated molecular patterns. Moreover, research evidence shows that the mechanisms through which platelets affect inflammatory responses and regulate hemostasis are the same. The roles of nucleotides and platelets in inflammation have been explored in several studies worldwide. Although platelets and nucleotides have unique structures, both of them influence the host response to pathogens and tumors. Analysis of platelets and nucleotides will offer valuable insight for the development of new treatments for infectious and inflammatory diseases.

Multiple Sclerosis (MS) is a neurological disease that affects the central nervous system (CNS). The diagnosis of the disease is quite challenging due to its variation among patients. As a result, the need to enhance diagnostic procedures, evaluate objective prognostic markers and promote effective monitoring of patients' responses to treatment has prompted the identification of many biomarkers. To present up-to-date knowledge on potential biomarkers for MS used to assess disease activity, progression, and therapeutic responses. The search for articles was conducted in various databases, namely, PubMed, Cochrane Library, and CINAHL, using an identical search strategy and terms that included "Multiple Sclerosis," "MS," "biomarkers," "potential," "magnetic resonance spectroscopy," "progress," "marker," "predict," "disability," "indicator," and "mass spectrometry." Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed when scrutinizing the articles for inclusion in the study. The search process identified 75 articles that were used in this systematic review. MS biomarkers consisted of laboratory biomarkers, imaging biomarkers, and genetic and immunogenetic biomarkers. The efficacy, which leads to their potential classification, relies on numerous factors, such as sensitivity, specificity, clinical rationale, predictability, practicality, biological rationale, reproducibility, and correlations with prognosis and disability. Oligoclonal bands (OCBs) and magnetic resonance imaging (MRI) features are the most established biomarkers so far, although kappa free light chains (kFLCs), the measles-rubella-zoster (MRZ) reaction, and neurofilament light chains (NfLs) might show potential in the near future after more studies are conducted., (Copyright © 2021 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Multiple sclerosis (MS) is a complex autoimmune disorder characterized by neurologic dysfunction. The symptoms worsen as the disease progresses to the relapsing stage., Aim: This study aimed to examine the role of T cells in MS pathogenesis., Materials and Methods: The review was performed based on articles obtained from PsycINFO, PubMed, Web of Science, and CINAHL. Search terms and phrases, such as "multiple sclerosis," "MS," "T cells," "development," "Dysregulated T cells," and "Effector T cells", were used to identify articles that could help explore the research topic., Results: The pathogenesis of MS is linked to the regulatory, inflammatory, suppressive, and effector roles of T cells. However, the actual roles of specific T cell subsets in MS development are not well understood., Discussion: The study revealed a significant link between MS and T cell activity. Targeting T cells is a potential strategy for the development of new therapies to manage MS., Conclusion: MS is a complex demyelinating condition that affects several million people around the world. Research has revealed that various classes of T cells, including effector T cells and regulatory T cells, influence the development and progression of MS. Further investigations are required to elucidate the underlying mechanisms through which specific T cell populations influence MS pathogenesis., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Significant advances have been observed in the field of cell biology, with numerous studies exploring the molecular genetic pathways that have contributed to species evolution and disease development. The current study adds to the existing body of research evidence by reviewing information related to the role of leftover viruses and/or viral remnants in human physiology. To explore leftover viruses, their incorporation, and their roles in human physiology. The study entailed conducting a systematic search in the PsycINFO, PubMed, Web of Science, and CINAHL databases to locate articles related to the topic of investigation. The search terms included "leftovers," "viruses," "genome sequences," "transposable elements," "immune response," and "evolution." Additional articles were selected from the references of the studies identified in the electronic databases. Evidence showed that both retroviruses and nonretroviruses can be integrated into the human germline via various mechanisms. The role of leftover viruses in human physiology has been explored by studying the activation of human retroviral genes in the human placenta, RNA transfer between neurons through virus-like particles, and RNA transfer through extracellular vesicles. Research evidence suggested that leftover viruses play key roles in human physiology. A more complete understanding of the underlying pathways may provide an avenue for studying human evolution and allow researchers to determine the pathogenesis of some viral infections. Evidence obtained in this review shows that leftover viruses may be incorporated into the human genome. Retroviral genes are critical for the development of different parts of the body, such as the placenta in mammals.

Various autoimmune diseases are associated with defects in protein degradation and NETosis. This review aims to examine defects in ubiquitination and NETosis and their associations with human disease. This study involved a systematic search of electronic databases, including PubMed, EBSCO, and LILACS, to locate articles on the relationship between human disease and defects in protein degradation and NETosis. Ubiquitination and NETosis can trigger a cascade of events that affect immune system function and impact the body's ability to fight disease. Ubiquitination is implicated in various disorders, such as Liddle's syndrome, Alzheimer's disease, and other neurodegenerative disorders, whereas NETosis has been linked to antineutrophil cytoplasmic antibody associated vasculitis, accelerated atherosclerosis, thrombosis, rheumatoid arthritis, antiphospholipid antibody syndrome, type 1 diabetes mellitus, and renal inflammatory complications. Researchers have attempted for years to identify the link between neurodegenerative disease and ubiquitination. Previous studies analysed the relationships between different autoimmune disorders and NETosis and identified various ubiquitin conjugates and NET remnants that trigger disease development and progression. Ubiquitination and NETosis play key roles in the emergence and progression of neurodegenerative and autoimmune disorders. Further investigation is needed to elucidate the mechanisms underlying the relationships between these disorders and biological processes., (Copyright © 2021 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Bariatric surgery has emerged as an effective treatment option in morbidly obese patients with non-alcoholic fatty liver disease (NAFLD). However, worsening or new onset of non-alcoholic steatohepatitis (NASH) and fibrosis have been observed. Caspase-cleaved keratin 18 (ccK18) has been established as a marker of hepatocyte apoptosis, a key event in NASH development. Thus, ccK18 measurements might be feasible to monitor bariatric surgery patients. Clinical data and laboratory parameters were collected from 39 patients undergoing laparoscopic Roux-en-Y gastric bypass at six timepoints, prior to surgery until one year after the procedure. ccK18 levels were measured and a high-throughput analysis of serum adipokines and cytokines was carried out. Half of the cohort's patients (20/39) presented with ccK18 levels indicative of progressed liver disease. 21% had a NAFLD-fibrosis score greater than 0.676, suggesting significant fibrosis. One year after surgery, a mean weight loss of 36.87% was achieved. Six and twelve months after surgery, ccK18 fragments were significantly reduced compared to preoperative levels ( p < 0.001). Yet nine patients did not show a decline in ccK18 levels ≥ 10% within one year postoperatively, which was considered a response to treatment. While no significant differences in laboratory parameters or ccK18 could be observed, they presented with a greater expression of leptin and fibrinogen before surgery. Consecutive ccK18 measurements monitored the resolution of NAFLD and identified non-responders to bariatric surgery with ongoing liver injury. Further studies are needed to elicit the pathological mechanisms in non-responders and study the potential of adipokines as prognostic markers.

Background: Closure or amputation of the left atrial appendage (LAA) is a common therapy for atrial fibrillation (AF). As the LAA is a hormone-producing organ, however, amputation is still somewhat controversial. We examined patients after surgical AF therapy with or without LAA amputation to determine the influence of LAA amputation on pro-atrial natriuretic peptide (proANP) and B-type natriuretic peptide (BNP) plasma levels and on clinical severity of heart failure., Methods: Twenty-one consecutive patients were prospectively randomized to either undergo LAA amputation ( n  = 10) or no LAA amputation ( n  = 11) between 05/2015 and 10/2015. All patients underwent coronary and/or valve surgery and concomitant AF surgery with either cryoablation ( n  = 3) or radio frequency ablation ( n  = 17). ProANP and BNP levels were measured preoperatively and until 800 days postoperatively., Results: Baseline proANP values were comparable between the groups (without LAA amputation: 4.2 ± 2.1 nmol/L, with LAA amputation: 5.6 ± 3.6 nmol/L). Postoperatively, proANP levels rose markedly in both groups. Even after LAA amputation, proANP levels remained elevated for 7 days postoperatively but fell to baseline levels at day 31 and remained on baseline level at 800 days postoperatively. ProANP levels in the LAA amputation group (5.8-9.7 nmol/L) were not significantly lower than in the group without LAA amputation (9.2-14.1 nmol/L; p  = 0.357). BNP levels also rose after surgery in both groups until day 7. At 800 days after surgery, BNP levels were back at baseline levels in both groups. Clinical follow-up at 2 years postoperatively showed no difference in heart failure symptoms or need for heart failure medication between the groups., Conclusion: In contrast to commonly held beliefs about the endocrine and reservoir functions of the LAA, there seems to be no clinically relevant detrimental effect of LAA amputation on natriuretic peptide levels and severity of heart failure until up to 2 years postoperatively., Competing Interests: The authors declare that there are no conflicting financial or nonfinancial interests with relevance to this manuscript., (Thieme. All rights reserved.)

Background: Neutrophil extracellular traps (NETs) have been implicated in host immune responses. Attempts have been made to examine how NETs affect the pathogenesis of complications such as autoimmune and vascular disorders. Aim: This study aimed to explore the relationship between NETs and vasculitis. Material and Methods: The current study entailed the searching of PsycINFO, PubMed, Web of Science, and CINAHL for articles related to the research topic. The search terms and phrases included "vasculitis," "NETs," "neutrophil extracellular traps," "NETosis," and "pathogenesis." The search was limited to articles published between 2009 and 2019. Results: Researchers have shown that NETs contribute to the pathogenesis of vasculitis through different mechanisms and processes, including renal failure and vascular damage. The protective effects of NETs have also been highlighted. Discussion: Overall, some scholars have shown the effectiveness of using DNase I and the PAD4 inhibitor Cl-amidine to treat vasculitis by restricting NET formation. However, observations have been noted in only animal experimental models. Conclusion: Neutrophil hyperactivity and its role in vasculitis are not yet fully understood. More studies aiming to determine the accurate function of NETs in vasculitis pathogenesis, particularly in humans, should be undertaken. Intensive research on NETs and vasculitis can increase the knowledge of medical practitioners and contribute to the development of new treatment methods to enhance patient outcomes in the future., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The innate immune system acts rapidly in an identical and nonspecific way every time the body is exposed to pathogens. As such, it cannot build and maintain immunological memory to help prevent reinfection. Researchers contend that trained immunity is influenced by intracellular metabolic pathways and epigenetic remodeling. The purpose of this review was to explore the topic of trained innate immunity based on the results of relevant previous studies. This systematic review entailed identifying articles related to trained innate immunity. The sources were obtained from PubMed using different search terms that included "trained innate immunity," "trained immunity," "trained," "innate," "immunity," and "immune system." Boolean operators were used to combine terms and phrases. A review of previous study results revealed that little is currently known about the molecular and cellular processes that mediate or induce a trained immune response in animals. However, it is believed that alterations in the phenotypes of cell populations and the numbers of specific cells may play a critical role in mediating the trained immune response. Increasing evidence shows that the protective processes and actions that occur during a secondary infection are not entirely linked to the adaptive immune system. Instead, these events also involve heightened activation of innate immune cells. While trained innate immune cells may have a shorter memory, they assist in the fight against pathogens and provide cross-protection. Identification of the mechanisms and molecules that underlie trained innate immunity has highlighted important features of the human immune response. Such advances continue to open doors for future research on how the body responds to disease-causing pathogens.

The mechanism underlying the pathogenesis of diabetes is complex and poorly understood. Recent investigations have revealed that insulin gene mutations can lead to the development of specific subtypes of diabetes. This systematic review aimed to explore the associations of insulin gene mutations and insulin translocation defects with diabetes. This review was generated using articles from PsycINFO, PubMed, Web of Science, and CINAHL. Search terms and phrases such as "diabetes," "mutations," "insulin," "preproinsulin," "INS gene," "role," "VNTR polymorphisms," and "INS promotor" were used to identify articles relevant to the research topic. The gathered data showed the significant role of insulin gene mutations and insulin translocation defects during diabetes development and progression. Genetic changes can adversely affect the development of various types of diabetes, such as neonatal diabetes mellitus and MIDY. Genetic alterations can affect insulin production, thus compromising the regulation of glucose utilization by tissues. Targeting insulin gene mutations is a potential new avenue for diagnosing and managing diabetes. There are specific subcategories of diabetes, such as MIDY and neonatal diabetes mellitus, caused by insulin gene mutations and defects in posttranslational modification. Further investigations are needed to examine the diagnostic and therapeutic potential of mutation-based biomarkers.

Background: Prediction, early diagnosis, and therapy of cardiac surgery-associated acute kidney injury (CSA-AKI) are challenging. We prospectively tested a staged approach to identify patients at high risk for CSA-AKI combining clinical risk stratification and early postoperative quantification of urinary biomarkers for AKI., Methods: All patients, excluding those on chronic hemodialysis, undergoing scheduled surgery with cardiopulmonary bypass between August 2015 and July 2016 were included. First, patients were stratified by calculating the Cleveland clinic score (CCS) and the Leicester score (LS). In high-risk patients (defined as LS > 25 or CCS > 6), urinary concentrations of biomarkers for AKI ([TIMP-2]*[IGFBP-7]) were evaluated 4 hours postoperatively. CSA-AKI was observed until postoperative day 6 and classified using the Kidney Disease: Improving Global Outcomes criteria., Results: AKI occurred in 352 of613 patients (54%). In high-risk patients, AKI occurred more frequently than in low-risk patients (66 vs. 49%; p  = 0.001). In-hospital mortality after AKI stage 2 (15%) or AKI stage 3 (49%) compared with patients without AKI (1.8%; p  = 0.001) was increased. LS was predictive for all stages of AKI (area under the curve [AUC] 0.601; p  < 0.001) with a poor or fair accuracy, while CCS was only predictive for stage 2 or 3 AKI (AUC 0.669; p  < 0.001) with fair accuracy. In 133 high-risk patients, urinary [TIMP-2]*[IGFBP-7] was significantly predictive for all-stage AKI within 24 hours postoperatively (AUC 0.63; p  = 0.017). However, for the majority of AKI (55%), which occurred beyond 24 hours postoperatively, urinary [TIMP-2]*[IGFBP-7] was not significantly predictive. Sensitivity for all-stage AKI within 24 hours was 0.38 and specificity was 0.81 using a cutoff value of 0.3., Conclusion: CSA-AKI is a relevant and frequent complication after cardiac surgery. Patients at high risk for CSA-AKI can be identified using clinical prediction scores, however, with only poor to fair accuracy. Due to its weak test performance, urinary [TIMP-2]*[IGFBP-7] quantification 4 hours postoperatively does not add to the predictive value of clinical scores., Competing Interests: The authors declare that there are no conflicting financial or nonfinancial interests with relevance to this article., (Georg Thieme Verlag KG Stuttgart · New York.)

Multiple sclerosis (MS) is a common, severe neurological disease that affects millions of people worldwide. Nevertheless, the actual cause of MS remains unknown. Smoking has been studied with respect to MS development and progression. The objectives of this review were to examine the relationship between smoking and MS and to understand the possible molecular mechanisms underlying the association. PubMed was searched for articles related to the study topic published between 2012 and 2020 using the search terms "multiple sclerosis," "smoking," "risk factors," "cigarettes," and "molecular mechanisms." Studies show a significant relationship between smoking and the risk of MS. Furthermore, smoking has been linked to the progression of MS at the patient and population levels. However, the underlying mechanism remains to be explored in further studies; researchers still disagree on how the relationship between smoking and MS arises in different populations. Evidence from randomized controlled trials, systematic reviews, and epidemiological studies shows that smokers have a higher risk of developing MS and experiencing related adverse symptoms and complications., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background : Incompatibilities between the mother and unborn baby can cause complications that must be identified early to initiate the appropriate treatment. For example, neonatal alloimmune thrombocytopenia (NAIT), neonatal alloimmune neutropenia (NAIN), and morbus hemolyticus neonatorum affect children worldwide. Aim : This literature review aims to depict the similarities and differences between these three disorders from a clinical and mechanistic point of view. Material and Methods : The current literature review entailed conducting a systematic search to locate articles on the three conditions. Different electronic databases, including PsycINFO, PubMed, Web of Science, and CINAHL, were searched using the search terms "neonatal alloimmune thrombocytopenia", "neonatal alloimmune neutropenia", "morbus hemolyticus neonatorum", "NAIT", "FNAIT", "fetal", "NAIN", and "hemolytic disease of the newborn". Results : This review shows that these three diseases are caused by incompatibilities between the maternal and fetal immune systems. Furthermore, these conditions can lead to severe complications that hinder fetal development and cause death if not well managed. Discussion: The current literature review shows that NAIT, NAIN, and morbus hemolyticus neonatorum are rare conditions that occur when the mother produces antibodies against the fetal immune system. Thus, there is a need for the early detection of these conditions to initiate appropriate treatment before the child experiences adverse effects. Conclusion : The development of NAIT, NAIN, and morbus hemolyticus neonatorum is linked to the production of antibodies against the fetal immune system and fetal antigens. Further studies are required to determine potential interventions to reduce the risk of developing these three conditions.

Background: Inflammation increases diabetes mellitus type 2 (T2DM) progression and severity. T2DM patients are at high risk of the rapid development of chronic periodontitis (CP). Topical presence, high numbers, and bactericidal effects of immune cells are challenged by augmented antigen-induced inflammation, which promotes both diseases., Objectives: To investigate gingival cellular inflammatory responses in individuals with previously undiagnosed T2DM with CP or CP alone and in systemically and periodontally healthy controls (H) in vivo and to establish an ex vivo technique permitting quantitative and qualitative assessments of gingival crevicular immune cells., Materials and Methods: T2DM + CP, CP, and H individuals (n = 10, each) received a 2-week oral hygiene regimen (OHR). Afterwards, a noninvasive sampling technique was performed to evaluate gingival inflammation induced under standardized conditions in vivo, that is, in the absence of severe periodontal destruction and inflammation at clinically healthy sites. Stimuli (casein/test or phosphate-buffered saline w/o. Ca 2+ or Mg 2+ , PBS (-/-) /control) were randomly applied contralaterally in the gingival sulci of participants' upper dentes canini. One day after completion of the OHR, gingival crevicular fluid (GCF) was kinetically assayed between the time of the baseline (BL) measurement and 55 minutes. Polymorphonuclear leukocyte (PMN) content (PMN GCF ) was quantitated at an optimum time of 35 minutes. PMN GCF counts reflect local inflammation. Ex vivo samples were fluorimetrically labeled, gated according to the donor's peripheral blood polymorphonuclear neutrophils (PMN PB ), and then counted, employing flow cytometry., Results: PMN GCF counts in unstimulated gingival crevices (at BL) in the T2DM + CP group were higher than those in the CP and H groups. PMN GCF counts were elevated in casein vs PBS (-/-) -stimulated gingival crevices in all groups. Patients with T2DM + CP showed increased PMN GCF counts compared to those with CP (P = .035) according to scatter plots. CD45 + counts in the stimulated sites in T2DM + CP patients were higher than those in CP and H patients (P = .041). Under stimulation conditions, the CD45 + counts differed from those under placebo conditions (P = .019), indicating augmented, inducible inflammatory leukocyte infiltrate in T2DM + CP patients., Conclusions: This noninvasive technique permits quantitative assessment of (experimental) gingival inflammation in vivo, revealing an influence of T2DM + CP on the number of primary immune cells in the gingival crevice. Patients who are challenged with (local) leukocytosis are likely at risk of collateral damage to the gingival crevice neighboring tissues, favoring the severity and progression of CP and consequently T2DM (www.clinicaltrials.gov NCT01848379)., (© 2020 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Background and Objectives: The tumor microenvironment has been widely implicated in tumorigenesis because it harbors tumor cells that interact with surrounding cells through the circulatory and lymphatic systems to influence the development and progression of cancer. In addition, nonmalignant cells in the tumor microenvironment play critical roles in all the stages of carcinogenesis by stimulating and facilitating uncontrolled cell proliferation., Aim: This study aims to explore the concept of the tumor microenvironment by conducting a critical review of previous studies on the topic. Materials and Methods: This review relies on evidence presented in previous studies related to the topic. The articles included in this review were obtained from different medical and health databases., Results and Discussion: The tumor microenvironment has received significant attention in the cancer literature, with a particular focus on its role in tumor development and progression. Previous studies have identified various components of the tumor microenvironment that influence malignant behavior and progression. In addition to malignant cells, adipocytes, fibroblasts, tumor vasculature, lymphocytes, dendritic cells, and cancer-associated fibroblasts are present in the tumor microenvironment. Each of these cell types has unique immunological capabilities that determine whether the tumor will survive and affect neighboring cells., Conclusion: The tumor microenvironment harbors cancer stem cells and other molecules that contribute to tumor development and progression. Consequently, targeting and manipulating the cells and factors in the tumor microenvironment during cancer treatment can help control malignancies and achieve positive health outcomes., Competing Interests: The author declares no conflict of interest.

We determined the prevalence of autoantibodies against an extended number of established and novel neural antigens in children and adolescents with suspected autoimmune encephalitis, epilepsy, single seizures, or marked epileptiform activity in electroencephalography (EEG). Prospectively, 103 patients were recruited aged between 0 and 18 years and 104 controls. A panel of 35 autoantibodies against neural cell-surface and intracellular antigens was screened. Sixteen of 103 patients (15.5%) showed a positive result for 1 or more autoantibodies, compared to 6 of 104 controls (5.8%, P = .02). Neurochondrin was identified as a possible new target of autoantibodies in 3 patients within this cohort, but none in controls. The patients showed severe behavioral disturbances, memory and cognitive impairment, episodes of reduced responsiveness, but no seizures, and normal MRI. Clinical findings, course, and treatment response of these 3 patients are presented.

Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by the production of autoantibodies specific for components of the cell nucleus and that causes damage to body tissues and organs. The pathogenesis of SLE remains unclear, with numerous studies pointing to a combination of genetic and environmental factors. A critical stage in SLE development is cell necrosis, in which undegraded chromatin and nucleoproteins are released into the blood, resulting in circulating cell-free DNA and serum nucleoproteins that trigger anti-dsDNA autoantibody production. This systematic literature review aimed to examine whether SLE stems from a DNA degradation and elimination defect. Materials and Methods: An advanced literature search was conducted in PubMed using the following keywords: [("SLE" OR "Systemic Lupus Erythematosus" OR "Lupus")] AND [("DNA" OR "DNA Degradation")] AND [("Defect Elimination")]. More articles were obtained from the references of the identified articles and basic Google searches. Twenty-five peer-reviewed articles published within the past 10 years (2007-2018) were included for review. Results: The findings of each study are summarized in Tables 1 , 2 . Discussion and Conclusion: The etiopathogenesis of SLE remains controversial, which limits therapeutic inventions for this disease. However, SLE is a DNA degradation and elimination disorder caused by uncleared histones and nuclear material that leak into the extracellular space and form cell-free DNA, triggering an immune response that destroys tissues and organs. Under normal conditions, apoptosis allows DNA and other nuclear material to be efficiently cleared through degradation and additional complex mechanisms such that this material does not trigger the immune system to produce nuclear autoantibodies.