Immune Disturbances Research Articles

Multidimensional study of the oral microbiome, metabolite, and immunologic environment in peanut allergy

The oral mucosa is the initial interface between food antigens, microbiota, and mucosal immunity, yet, little is known about oral host-environment dynamics in food allergy. Our aim was to determine oral microbial, metabolic, and immunologic profiles associated with peanut allergy. We recruited 105 subjects (56 with peanut allergy and 49 healthy subjects) for salivary microbiome profiling using 16S ribosomal RNA sequencing, short-chain fatty acid (SCFA) metabolite assays using liquid chromatography/mass spectrometry, and measurement of oral secreted cytokines using multiplex assays. Analyses within and across data types were performed. The oral microbiome of individuals with peanut allergy was characterized by reduced species in the orders Lactobacillales, Bacteroidales (Prevotella spp), and Bacillales, and increased Neisseriales spp. The distinct oral microbiome of subjects with peanut allergy was accompanied by significant reductions in oral SCFA levels, including acetate, butyrate, and propionate, and significant elevation of IL-4 secretion. Decreased abundances of oral Prevotella spp and Veillonella spp in subjects with peanut allergy were significantly correlated with reduced oral SCFA levels (false discovery rate<0.05), and increased oral Neisseria spp was correlated with lower oral SCFA levels (false discovery rate<0.05). Additionally, oral Prevotella spp abundances were correlated with decreased local secretion of TH2-stimulating epithelial factors (IL-33 and thymic stromal lymphopoietin) and TH2 cytokines (IL-4, IL-5, and IL-13), whereas oral Neisseria spp abundance was positively associated with a TH2-skewed oral immune milieu. Our novel multidimensional analysis of the oral environment revealed distinct microbial and metabolic profiles associated with mucosal immune disturbances in peanut allergy. Our findings highlight the oral environment as an anatomic site of interest to examine host-microbiome dynamics in food allergy.

COVID-19 and obesity: what is known about the features of pathogenesis and treatment?

The increasing prevalence of overweight and obesity is a public health problem worldwide. During the COVID-19 pandemic, obesity is associated with a higher risk of severe disease and adverse clinical outcome of SARS-CoV-2 infection. It may be associated with chronic systemic inflammation, impaired immune response and metabolic disturbances in obese patients. In order to establish possible pathogenetic links between obesity and COVID-19, an analysis of experimental, clinical studies, their meta-analyzes, literature reviews from the PubMed/MedLine database was carried out using the keywords «COVID-19» and «obesity». This review discusses the potential pathogenesis and treatment features of obese patients with COVID-19.

Infections in systemic autoimmune diseases

IntroductionInfections are a major cause of morbidity and mortality in patients with systemic autoimmune diseases. The aim of the present study is to describe the frequency of infections in a historical cohort of the SAD polyclinic of the Maciel Hospital, according to the type of disease and treatment received. Material and methodsAn analytical, retrospective and observational study was conducted in 339 patients with SAD attended at the outpatient clinic in the period from January 1, 2012 to February 28, 2019. Infectious complications were analysed according to treatment and disease. Results339 cases, median age 56, mostly female. Most cases presented SLE (30.1%) and RA (23.6%), followed by antiphospholipid syndrome (20.4%) and Sjögren's syndrome (12.1%). Hydroxychloroquine (66%), followed by corticosteroids (55.5%) were the most frequently used treatments. Thirteen point three percent received biological therapies: 46.9% of the cases presented some infectious complication, 95% were non-opportunistic. Respiratory infections were the most frequent (48.6%) followed by urinary infections (31.7%) and skin and soft tissue infections (17.6%). On comparing the infected and non-infected groups, significant differences were found in the following variables: methotrexate, mycophenolate, corticoids, biological therapies, combination of drugs, active disease, RA and cases with overlap. The use of hydroxychloroquine and sulfasalazine was associated with a lower risk of infection in patients with RA. ConclusionsInfections are a frequent complication in patients with RA, due to the immune disturbances of the disease itself and prescribed treatments, mainly corticoids and biologicals. The importance of screening and infection prophylaxis before starting treatment is stressed.

CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus.

Background: End-stage renal disease (ESRD) is associated with alterations in T-cell immunity, including increased CD28null and reduced regulatory T cells (Tregs). However, whether immune disturbances are due to ESRD or primary disease is not yet clear. As diabetes mellitus is the leading cause of ESRD, we evaluated its impact on the immune profile of ESRD patients. Methods: CD28null, Tregs, and natural killer cells were initially analyzed by flow cytometry in 30 predialysis ESRD patients due to diabetes (DM), 30 non-DM (NDM), and 25 healthy controls. Measurements were repeated after 6 months on hemodialysis (HD) or peritoneal dialysis (CAPD). Results: The percentage of CD4 + CD28null cells, CD8 + CD28null cells, and Tregs showed significant differences in DM, NDM, and controls; mean rank 33.71 vs. 25.68 vs. 18.88, p = 0.006, 37.79 vs. 28.82 vs. 17.08, p = 0.008, and 20.79 vs. 26.12 vs. 41.33, p = 0.001, respectively. DM vs. NDM had increased CD4 + CD28null and CD8 + CD28null cells, 11.5% (1.5%–24%) vs. 4.1% (0–42.3%), p = 0.02 and 61.3% (24%–76%) vs. 43% (5.7%–85%), p = 0.04, respectively. After 6 months on HD but not CAPD, DM showed a significant further increase in CD4 + CD28null cells, from 30 (14–100) to 52.7 (15–203), p = 0.02; and CD8 + CD28null cells, from 137 (56–275) to 266 (103–456), p = 0.01. Conclusions: Diabetes mellitus affects T-cell subtypes even at predialysis stage, though changes become more prominent after commencement on HD.

MicroRNAs in the interaction between host-bacterial pathogens: A new perspective.

Gene expression regulation plays a critical role in host-pathogen interactions, and RNAs function is essential in this process. miRNAs are small noncoding, endogenous RNA fragments that affect stability and/or translation of mRNAs, act as major posttranscriptional regulators of gene expression. miRNA is involved in regulating many biological or pathological processes through targeting specific mRNAs, including development, differentiation, apoptosis, cell cycle, cytoskeleton organization, and autophagy. Deregulated microRNA expression is associated with many types of diseases, including cancers, immune disturbances, and infection. miRNAs are a vital section of the host immune response to bacterial-made infection. Bacterial pathogens suppress host miRNA expression for their benefit, promoting survival, replication, and persistence. The role played through miRNAs in interaction with host-bacterial pathogen has been extensively studied in the past 10 years, and knowledge about these staggering molecules' function can clarify the complicated and ambiguous interactions of the host-bacterial pathogen. Here, we review how pathogens prevent the host miRNA expression. We briefly discuss emerging themes in this field, including their role as biomarkers in identifying bacterial infections, as part of the gut microbiota, on host miRNA expression.

Structural and Functional Dysbiosis of Fecal Microbiota in Chinese Patients With Alzheimer's Disease.

Increasing evidence suggests that gut dysbiosis plays vital roles in a variety of gut–brain disorders, such as Alzheimer's disease (AD). However, alterations of the gut microbiota as well as their correlations with cognitive scores and host immunity have remained unclear in well-controlled trials on Chinese AD patients. In this study, samples from 100 AD patients, and 71 age- and gender-matched, cognitively normal controls were obtained to explore the structural and functional alterations of the fecal microbiota targeting the V3–V4 region of the 16S rRNA gene by MiSeq sequencing, and to analyze their associations with clinical characteristics. Our data demonstrated a remarkably reduction in the bacterial diversity and alterations in the taxonomic composition of the fecal microbiota of the AD patients. Interestingly, the abundant butyrate-producing genera such as Faecalibacterium decreased significantly, where this was positively correlated with such clinical indicators as the MMSE, WAIS, and Barthel scores in the AD patients. On the contrary, abundant lactate-producing genera, such as Bifidobacterium, increased prominently, and were inversely correlated with these indicators. This shift in the gut dysbiosis of the microbiota, from being butyrate producers to lactate producers, contributed to immune disturbances in the host that could be used as non-invasive biomarkers to distinguish the controls from the AD patients. Moreover, several predicted functional modules, including the biosynthesis and the metabolism of fatty acids, that were altered in the microbiota of the AD patients could be utilized by the bacteria to produce immunomodulatory metabolites. Our study established the structural and functional dysbiosis of fecal microbiota in AD patients, and the results suggest the potential for use of gut bacteria for the early, non-invasive diagnosis of AD, personalized treatment, and the development of tailor-made probiotics designed for Chinese AD patients.

Allergy & Immunology Involvement on Multidisciplinary Treatment Team During COVID-19 Pandemic

As clinical immunologists, we are experts in immune dysregulation as we regularly treat patients with combined immune deficiency and autoimmunity. This places us in a unique position to understand the nuances of COVID-19 immune disturbances, including cytokine release syndrome, and make recommendations regarding treatment. At our institution, Allergy and Immunology faculty and fellows participated on a multidisciplinary COVID-19 treatment team whose role was to develop and revise a treatment algorithm for admitted patients and review patient charts under a stewardship module in the EMR. Outcome data for patients admitted with SARS-CoV-2 infection from March 10 to 31, 2020 was analyzed. Severe disease was defined as requiring at least 3L of oxygen to maintain SpO2 >93%. A treatment algorithm with recommendation for tocilizumab for patients requiring 3L/min of oxygen or greater to maintain SpO2 >93% was developed. The treatment algorithm included consideration of Allergy and Immunology consultation if there was need for repeat or alternative biologic agents. A total of 239 patients with PCR-confirmed SARS-CoV-2 infection were included. 153 of 239 patients received tocilizumab. Of all patients, 25 of 239 died, for an overall mortality rate of 10.5%. Among tocilizumab-treated patients requiring mechanical ventilation, survival was 75% (95% CI, 64-89). The presence of a multidisciplinary treatment team, treatment algorithm, and stewardship module involving Allergy and Immunology was associated with favorable mortality outcomes for patients affected by COVID-19. Involvement of Allergy fellows on the multidisciplinary team supported learning opportunities for fellows via collaboration with other specialists.

Role of Anxiety and Depression in Altering Immune System Associated with Breast Cancer. Systematic Review

Background: Focusing on basic and clinical research, psycho-neuroimmunology researchers are looking at how the factors that cause anxiety and depression and their negative emotions can affect physiological and health conditions. Clinical studies have shown that the central nervous system is associated with endocrine and immune systems. Objectives: To investigate the impact of depression and anxiety on developing breast cancer through immune disturbance pathway Methodology: The present study is a descriptive review of systematic review studies conducted in accordance with the guidelines for preferred cases for reporting systematic and meta-analysis review articles (prisma). Electronic databases including ISI Web of Knowledge, PubMed, and Scopus, were searched from 2012 to 2020. The search strategy psychological, immune response, anxiety disorder, depression, and psychoneuroimmunology. Additionally, we searched the references of retrieved articles to find additional included a combination of the following Medical Subjects Headings (MeSH) terms: breast cancer, potentially related studies. We have considered herbal therapies, which were applied orally, or topically. The content of all articles was evaluated qualitatively after extracting from the desired databases with PRISMA checklist. Results: the impact of psychological problems on people’s illness is very large, when people have a lot of psychological pressure, the incidence will be higher than ordinary people. Health Psychology considers human health to be a complex entity and believes that disease is not caused by a single factor but is the product of biological, psychological, and social factors. Recent research has previously confirmed the effect of psychosocial factors such as stress and how it reacts to the onset and course of the disease. Most of the patients with malignant tumor had negative emotional problems such as anxiety and depression. Depression in cancer is markedly different from depression in healthy individuals, and involves a unique symptomatology and a strong biological etiology. Conclusions: A better understanding of the bidirectional communication between the neuroendocrine and immune systems could contribute to new clinical and treatment strategies.

Single-cell transcriptomics uncovers phenotypic alterations in the monocytes in a Chinese population with chronic cadmium exposure

BackgroundCadmium is the most prevalent form of heavy metal contaminant globally and its exposure rises serious health concern. Chronic exposure to cadmium causes immune disturbances. However, few studies have addressed how it affects circulating immune cells, one of the most essential elements for the host defense system, at both population and molecular level. Therefore, this is the first single-cell transcriptomic analysis of the response of the human circulating immune system to plasma cadmium level. MethodsWe conducted a cross-sectional study in Hunan province, which has the highest level of cadmium land contamination in China. A total of 3283 individuals were eligible for analyzing the association between plasma cadmium levels and the monocyte counts and its subgroups. Another 780 individuals were assigned for validation. Thirty propensity-matched individuals without chronic disease from the lowest- and highest-quartile groups according to serum cadmium levels were selected for single-cell RNA sequencing (scRNA-seq) and flow cytometry analyses. Moreover, the monocyte phenotypic alterations in the heavy metal-exposed population were validated with a cecal ligation and puncture sepsis mouse model. ResultsFrom August 2016 to July 2017, we conducted a cross-sectional study to identify phenotypic alterations in peripheral immune cells in cadmium polluted areas in China. Monocyte percentages were negatively associated with plasma cadmium levels in multivariable linear regression analysis. Peripheral blood mononuclear cell scRNA-seq revealed that the CD14+ monocyte subset was dramatically reduced in the highest-quartile cadmium-exposed group. Moreover, we assessed different hallmarks of immune cell dysfunction—such as host defense capability, apoptotic signaling, cellular diversity and malignant gene expression in monocytes. Importantly, cadmium induced phenotypic alterations in the immune system were validated in the cecal ligation and puncture sepsis mouse model, in which chronic exposure to cadmium not only increased the death rate but also decreased monocyte numbers and the ability to clear bacterial infections. ConclusionThis transcriptomic analysis provides molecular information about how the most important hallmarks of immune cell dysfunction are affected by plasma cadmium level. The significant phenotypic alterations in monocytes serving as early indicators of increased susceptibility to infectious and malignant diseases.

Corrective effects of original bioflavonoid complex in the cyclophosphamide-induced immunity disorders

Our aim was to evaluate immunomodulatory properties of an original bioflavonoid complex in experimental immune disturbances induced by cyclophosphamide (Cy). We have studied morphometric indexes of thymus and spleen, as well as blood leukocyte counts, cell proliferative activity in lymphoid organs, delayed hypersensitivity responses to T cell-dependent antigen, along with differentiation activity of bone marrow stem cells in experimental animals during Cy-induced immune suppression after a course of bioflavonoid treatment. Suspension of the bioflafonoid complex was introduced to the male mice (СВАхC57Bl/6)F1 aged 12- 14 weeks at a daily dose of 2 mg/animal (80 mg/kg), per os, using gastric catheter, over 14 days. Cytostatic immunosuppression was produced by a single intraperitoneal Cy injection. Proliferative activity of spleen and thymic cells was determined by standard method with Н3 -thymidine incorporation in the 72-h cell culture. Cellular immune response was assayed by the degree of delayed-type hypersensitivity development in response to sheep erythrocytes. The number of hematopoietic progenitors was evaluated by culturing bone marrow cells in methylcellulose-based medium. The experiments have shown mitigation of immunosuppressive effects induced by Cy, in the course of bioflavonoid complex treatment, with respect to absolute and relative mass of lymphoid organs and leukocyte numbers in peripheral blood. Moreover, we have demonstrated decreased effects of Cy treatment upon the spontaneous activity of spleen cells, mitogen-induced thymocyte and splenocyte proliferation, intensivity of delayed-type hypersensitivity response that reached the values of intact animals. Following the course of bioflavonoids, we have revealed an increase in early hematopoietic progenitors. Alleviation of Cy-induced suppressive effects upon cellular immune response, proliferation rates of immune cells, as well as stimulation of hematopoietic stem cell functions suggest a sufficient capacity of the original bioflavonoid complex for modulation of immunity and hematopoiesis, thus presenting experimental proofs for its potential usage as an adjuvant treatment of the patients with malignant diseases.

Kawasaki Disease and Allergic Diseases.

Background: Kawasaki disease (KD) is an inflammatory disorder with an unknown etiology. It is the leading cause of acquired heart disease, which leads to coronary vasculitis among children. Studies of frequent manifestation of allergic diseases in children with KD have been the subject of mounting clinical interest. However, evidence supporting the association between KD and allergies has yet to be systematically reviewed.Methods: In this article, we reviewed current literature regarding the association between KD and allergic diseases. References for this review were identified through searches of PubMed, Cochrane, and Embase through the end of August 2020.Results: The results of the analyses of immune repertoire, clinical, and epidemiological studies have indicated some of the characteristics of infectious disease for KD. Although some allergic disorders, such as asthma, may be exacerbated by viral infections, allergies are typically caused by an allergen that triggers an immune response, with the potential involvement of type 2 inflammation and immune disturbances leading to tissue remodeling in genetically susceptible hosts. The effect of intravenous immunoglobulin is multi-faceted and results in a decrease in activating Fc gamma receptor IIA and an increase in anti-inflammatory eosinophils. The findings from this review demonstrate that children who have suffered from KD are more likely to have allergic rhinitis than the general population and their siblings, a condition that lasts until the age of 17. When followed up as teenagers and adults, children with KD are more likely to develop urticaria.Conclusions: This review supports that allergic diseases, such as allergic rhinitis, have been demonstrated to increase following KD. Therefore, the importance of allergic diseases in patients with KD should be emphasized in long-term care. Interventions that include strategies for managing allergies in children with KD would be beneficial.

Prognosis of amnestic mild cognitive impairment: clinical and immunological correlations

To determine the long-term (three-year) prognosis of the cognitive deficits progression in elderly people with amnestic mild cognitive impairment (aMCI) based on the analysis of the initial clinical and immunological parameters. This study is based on a clinical and follow-up study of 252 outpatients with aMCI, who were observed in the Federal State Budgetary Scientific Institution «Mental Health Research Center» from 2018 to 2020. The psychometric assessment complex included the following scales and tests: MMSE, MoCA, The 10 words test, BNT, David Wechsler's Scale, subtest 6, CDT, Memory test of 5 geometric shapes, BVRT Test, DRS - Mattis Dementia Rating Scale: Verbal fluency, DRS - Mattis Dementia Rating Scale, The Munsterberg Test. As part of the study, the level of cytokines (TNF-a, IL-1, IL-6, IL-8, IL-10) in the blood serum was determined in all patients by enzyme immunoassay (ELISA), using diagnostic kits manufactured by Cytokine LLC. In patients with a progression of aMCI syndrome, an increase in proinflammatory cytokines IL-1, IL-6, IL-8, TNF-α is initially detected, which may reflect the level of systemic inflammation or functional insufficiency of anti-inflammatory mechanisms. In turn, the group with a subsequent improvement in cognitive functioning, on the contrary, is distinguished by an initially increased level of the anti-inflammatory interleukin system (IL-10). We provide new data on the presence of systemic inflammation and immune disturbances and their association with clinical course of disease in the majority of elderly patients with aMCI. Signs of a chronic low-level systemic inflammatory response in patients with aMCI is the unfavorable prognosis criterion: in such patients, cognitive deficit significantly progresses or dementia due to Alzheimer disease develops within three years.

The relationship of morphometric changes of the brain with IL-6 levels, systemic inflammation and immune disturbances in the patients with schizophrenia

Schizophrenia is a chronic disease characterized by psychosis, behavioral, cognitive and social impairments. It is accompanied by structural and functional changes in the brain. To confirm the significance of morphometric changes, it is important to establish relationships between structural changes in the brain, clinical symptoms, and the level of biomarkers reflecting the pathogenesis of the disease, including immunological markers. The aim of this work was to assess the relationship of interleukin-6 (IL-6) levels with systemic inflammation, immune activation and with the results of neuroimaging in schizophrenia. The study included 60 patients with schizophrenia, 25 healthy volunteers. MRI scanning and the assessment of key immunological parameters was performed. It was found that the patients had significant negative correlations between IL-6 levels and a number of structural MRI indicators. Patients with a marked increase in IL-6 levels (>15 pg / ml) had a reduced mean curvature in the left lingual gyrus and a reduced gyrification index in the left fusiform gyrus compared with the control group. The level of IL-6 was associated with signs of systemic inflammation and immune activation in the patients. Thus, in this work, an immunological profile in schizophrenia associated with an increase in IL-6 and with morphometric changes of the brain was characterized for the first time. In further studies, we plan to evaluate morphometric changes in patients with various immunological phenotypes of schizophrenia, clinical course of the disease, and factors of genetic predisposition.

High-Fat Diet-Induced Fatty Liver Is Associated with Immunosuppressive Response during Sepsis in Mice.

High-fat diet-induced fatty liver is an indolent and chronic disease accompanied by immune dysfunction and metabolic disturbances involving numerous biological pathways. This study investigated how this abnormal metabolic disorder influences sepsis in mice. Mice were fed with normal chow (NC) or high-fat diet (HFD), and palmitic acid (PA) was used to treat hepatocytes to mimic fat accumulation in vitro. Lipopolysaccharide (LPS) was used to induce sepsis and related immune responses. Mice fed on a high-fat diet displayed higher mortality and more severe liver damage but compromised immunoreaction. The supernatant from PA-treated primary hepatocytes markedly diminished the inflammatory cytokine expression of macrophages after LPS stimulation, which showed a state of immunosuppression. Metabolomics analysis indicated the level of many key metabolites with possible roles in immunoreaction was altered in the HFD and PA groups compared with corresponding controls; specifically, β-hydroxybutyric acid (BHB) showed an immunosuppressive effect on Raw264.7 cells during the LPS stimulation. Transcriptomic analysis suggested that several differential signaling pathways may be associated with the alteration of immune function between the NC and HFD groups, as well as in the in vitro model. Our study suggests that the consumption of HFD may alter the hepatic metabolic profile, and that certain metabolites may remold the immune system to immunosuppressive state in the context of sepsis.

Role of Anxiety and Depression in Altering Immune System Associated with Breast Cancer. Systematic Review

Background: Focusing on basic and clinical research, psycho-neuroimmunology researchers are looking at how the factors that cause anxiety and depression and their negative emotions can affect physiological and health conditions. Clinical studies have shown that the central nervous system is associated with endocrine and immune systems. Objectives: To investigate the impact of depression and anxiety on developing breast cancer through immune disturbance pathway Methodology: The present study is a descriptive review of systematic review studies conducted in accordance with the guidelines for preferred cases for reporting systematic and metaanalysis review articles (prisma). Electronic databases including ISI Web of Knowledge, PubMed, and Scopus, were searched from 2012 to 2020. The search strategy psychological, immune response, anxiety disorder, depression, and psychoneuroimmunology. Additionally, we searched the references of retrieved articles to find additional included a combination of the following Medical Subjects Headings (MeSH) terms: breast cancer, potentially related studies. We have considered herbal therapies, which were applied orally, or topically.The content of all articles was evaluated qualitatively after extracting from the desired databases with PRISMA checklist. Results: the impact of psychological problems on people's illness is very large, when people have a lot of psychological pressure, the incidence will be higher than ordinary people.Health Psychology considers human health to be a complex entity and believes that disease is not caused by a single factor but is the product of biological, psychological, and social factors. Recent research has previously confirmed the effect of psychosocial factors such as stress and how it reacts to the onset and course of the disease. .Most of the patients with malignant tumor had negative emotional problems such as anxiety and depression .Depression in cancer is markedly different from depression in healthy individuals, and involves a unique symptomatology and a strong biological etiology. Conclusions: A better understanding of the bidirectional communication between the neuroendocrine and immune systems could contribute to new clinical and treatment strategies.

Candidal meningitis in disseminated candidiasis by Candida tropicalis - A rare case report from India

Introduction: Candida spp. are the normal flora of human body and do not cause CNS disease unless there is some immune disturbance. The prevalence of non albicans species differed significantly in various geographic areas. Candida tropicalis is a species that is now recognized as an important pathogen of debilitated individuals. Case Report: A 70 year old female complaining of altered sensorium since 7 days with neck stiffness. The patient was also had white plaques in the oral cavity and pharynx. MRI scan showed bilateral cerebral infarcts in pre and post central gyral regions and left thalamus. Thick curvilinear leptomeningeal enhancement along the bilateral parietal regions. Gram stain of centrifused CSF, throat swab showed presence of gram positive, yeast budding cells. Growth was curdy white on Saboraud’s dextrose agar and was negative for germ tube test. Blue colored colonies were obtained on Candida chrome agar and considered as Candida tropicalis. HIV status was negative. The patient was administered intravenous liposomal amphotericin B along with regular insulin, levitiracetam lobazam, pheytoin and potassium supplementation along with I.V. fluids. She was discharged from hospital with fluconazole maintenance dose. Conclusion: Candida tropicalis is now recognized as an important pathogen of debilitated individuals. Subclinical candidal colonization can make the individual more prone to develop systemic infection and disease. Candida tropicalis infects meningeal layers, brain parenchyma and also involves vasculature of brain. Even though Systemic infections with Candida tropicalis may occur as terminal complications, timely evaluation, accurate diagnosis, administration of specific and supportive treatment gives good prognosis. Keywords: Candida tropicalis, Disseminated, Meningoencephalitis, Amphotericin B.

The Relationship Between Serum Cytokine Levels and the Degree of Psychosis and Cognitive Impairment in Patients With Methamphetamine-Associated Psychosis in Chinese Patients.

Background: Cytokine levels can be changed in methamphetamine (METH) use disorders (MUDs) and primary psychosis. The present study assessed serum levels of some kinds of interleukins (ILs) in METH-associated psychosis (MAP) and their relationships with psychotic symptoms and cognitive dysfunction.Methods: Serum IL-2R, IL-6, IL-8, and IL-10 levels were examined by chemiluminescence assays in MAP patients (n = 119) and healthy controls (n = 108). The Positive and Negative Syndrome Scale (PANSS) and Montreal Cognitive Assessment (MOCA) were administered.Results: Serum levels of IL-6 and IL-8 were significantly increased in MAP patients (all p < 0.05). There was a negative relationship between IL-2R levels and PANSS positive (P) subscale scores (r = −0.193, p = 0.035). IL-6, IL-8 and IL-10 levels were all negatively correlated with the naming, delayed recall and orientation subscores on the MOCA (r = −0.209, p = 0.022; r = −0.245, p = 0.007; r = −0.505, p < 0.001, respectively).Conclusions: Our results indicate that immune disturbances are related to MAP and that IL-2R, IL-6, IL-8, and IL-10 are associated with the severity of psychotic symptoms and cognitive function impairment.

The combined action of monocytic myeloid-derived suppressor cells and mucosal-associated invariant T cells promotes the progression of cervical cancer.

One of the most common promoters of the initiation and growth of the tumor is an immune disturbance. Numerous immune cells and inflammatory factors play a role in the tumor-immune microenvironment. However, few studies have investigated the correlation between these immunological events and clinical consequences in cervical cancer. We measured the levels of numerous inflammatory mediators and frequencies of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs) and mucosal-associated invariant T (MAIT) cells in peripheral blood (PB) of cervical cancer patients. Cervical cancer patients showed elevated production of interleukin (IL)-18 and plasma C-C chemokine ligand (CCL) 3/5. Meanwhile, an accumulation of C-C chemokine receptor 5 (CCR5) monocytic (Mo)-MDSCs and Tregs was observed. The cervical cancer group displayed increased frequencies of CD8+ , CD4+ and highly activated CD38+ CD8+ MAIT cells, and reduction of double-negative (DN) and PD1(CD279+ ) DN MAIT cells. Importantly, it was demonstrated that MAIT cells were positively related to Mo-MDSCs. Furthermore, an elevated concentration of PD1(CD279+ ) DN MAIT cells was significantly related to increased progression-free survival of patients with cervical cancer. In conclusion, our study suggests that the combined action of Mo-MDSCs and MAIT cells might be associated with the progression of cervical cancer, and the frequency of DN MAIT cells in the peripheral blood mononuclear cells was associated with the survival benefit of patients.

Case Series of Chronic Inflammatory Rheumatic Disease Patients Infected by Coronavirus Disease 2019 (COVID-19)

Coronavirus disease 2019 (COVID-19) is a viral infection that appeared in December 2019. The risk of infection seems to be increased in chronic inflammatory rheumatic diseases due to both immune disturbances related to the disease and treatment. In this case report, we describe the clinical features of 5 rheumatic immune disease patients with the concomitant presence of COVID-19. Among these patients, 3 had rheumatoid arthritis and 2 had systemic lupus erythematosus. Patients' age ranged between 38 and 63 years. Only one patient (SLE) had a severe subtype of COVID-19. All the patients were cured of COVID-19 and were subsequently discharged.

Treatment with methotrexate carried in lipid core nanoparticles prevents the development of diastolic dysfunction in septic rats

Abstract Introduction In the development of sepsis, besides the dysregulation of the immune system and disturbances of several vital organs, life-threatening cardiac dysfunction often occurs. Previously, we showed that non-protein nanoparticles that resemble the lipid structure of low-density lipoprotein, termed LDE, concentrate in inflammatory sites. When incorporated in LDE, the cellular uptake of MTX increases several-fold compared to the uptake of commercial MTX. The novel LDE-MTX formulation was shown to have the ability to modulate the immune response in in rabbits with atherosclerosis and in rats with myocardial infarction. LDE-MTX reduced the inflammation and improved the post-infarction cardiac function by increasing the release of angiogenesis, thereby improving hypoxia. The aim of the current study was to test the hypothesis whether LDE-MTX could also improve the cardiac status in septic rats. Methods Septicemia was induced in Wistar rats by two I.P. injections of lipopolysaccharide (LPS, 10mg/kg) administered with a 24h interval. Rats were allocated to control group (CT, without sepsis; n=5) and 3 groups with sepsis: LDE (n=7), treated with LDE only; MTX (n=6), with commercial MTX (1mg/kg); and LDE-MTX (n=7), with LDE-MTX (1mg/kg). Echocardiography was performed 72h after sepsis induction. Animals were euthanised and LV tissues were collected for protein expression analysis of inflammatory, apoptotic, angiogenesis, hypoxia and adenosine bioavailability markers. Results Septic rats treated with LDE developed diastolic dysfunction and presented decreased diastolic volume and diameter of the LV. Treatment with LDE-MTX totally prevented the appearance of diastolic dysfunction and the alterations in LV diastolic dilation. Also, LDE-MTX treatment elicited cardiac hypertrophy through the increase of the thickness of septum and of the LV posterior wall. LDE-MTX increased LV mass and the relative heart weight, as compared to the other 3 groups. There were no differences in the protein expression of inflammatory (lymphocytes, tumor necrosis factor, interleukins) and apoptotic (caspases and B-cell lymphoma family) markers among the four groups. However, LDE-MTX showed higher expression of CD68 (macrophage marker). Angiogenesis was higher, while cellular hypoxia was lower in LDE-MTX, respectively represented by vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 alpha, in comparison to the other 3 groups. The intracellular adenosine bioavailability was increased in LDE-MTX-treated animals, as promoted by the higher expression of the A1 receptor, as compared to CT. Conclusion The treatment with LDE-MTX was successful in precluding the appearance of the cardiac dysfunction associated to sepsis. This outcome was conceivably attained by different effects of the treatment observed here, such as those on angiogenesis, macrophage recruitment and adenosine bioavailability in the LV. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)