Immunocompetent Research Articles

Consumption of a Probiotic Blend with Vitamin D Improves Immunity, Redox, and Inflammatory State, Decreasing the Rate of Aging—A Pilot Study

There is evidence of the effect of probiotic intake on the immune system. However, the effect probiotics may have on the rate of aging is unknown. The aim of this study is to determine the effect of a probiotic blend on immunity, redox state, inflammation, and the rate of aging or biological age. A group of 10 men and 14 women took, daily for 2 months, a sachet with three probiotics (Bifidobacterium animalis subsp. lactis BSO1, Lactobacillus reuteri LRE02, Lactobacillus plantarum LP14) and vitamin D. Before starting the treatment and after 2 months, peripheral blood was collected. Immune functions were assessed in isolated immune cells, and cytokine concentrations were also measured both in mononuclear cell cultures and plasma. Redox state parameters were also analyzed in whole blood cells. Finally, the Immunity Clock was applied to determine the biological age. Results show that the intake of this probiotic blend in general, in both men and women, improves immunity and decreases the oxidative and inflammatory state. In addition, it rejuvenates the biological age by 10 years on average. It can be concluded that this probiotic blend could be proposed as a good strategy to slow down the aging process, and to achieve healthy aging.

An institutional protocol including socket alveoplasty and primary closure following dental extractions for patients with an elevated risk of developing medication-related osteonecrosis of the jaw.

Background The purpose of this study was to evaluate the outcomes of alveoplasty and primary closure following dental extractions in patients with an elevated medication-related osteonecrosis of the jaw (MRONJ) risk.Study design A retrospective review of 46 patients with an elevated MRONJ risk was conducted. This included a total of 124 teeth extracted, due to unrestorable caries (n = 46; 37%) and peri-apical pathology (n = 44; 35%).Results Our results showed 0% (n = 0) of patients in our cohort developed MRONJ post-operatively. Most patients were being treated with intravenous zoledronic acid for breast cancer (n = 23; 50%), with an average of 15 doses (range 1-72).Conclusions This study supports the use of alveoplasty and primary closure for patients with an elevated MRONJ risk. The authors highlight the importance of pre-operative cone beam computed tomography imaging, optimisation of immune status, post-operative prophylactic antibiotics, and the delay of bone modifying agents recommencement as influential factors in mitigating risk and favouring successful outcomes.

Immune system dysfunction in personnel of chemical hazard facilities: purpose and effectiveness of immunotherapeutic drugs

Clinical signs of the presence of immune dysfunction/insufficiency, identified by questioning workers at the landfill for the storage and destruction of industrial toxic waste, were the basis for performing a screening study of immune status. This included a clinical blood test with determination of the leukocyte formula, assessment of the phenotypic status of lymphocytes for the main subpopulations, determination of the concentration in serum immunoglobulins of various classes, assessment of the migration activity of leukocytes, assessment of the microbicidal capacity of neutrophils and their ability to phagocytosis. When the examined employees were found to have more than 20% changes in the normative range of immune status parameters and the presence of combined disorders in different parts of immunoreactivity, in particular combined disorders in the cellular part of the immune system, it was the basis for conducting an in-depth stage of immunoepidemiological examination. This included determination of functional activity cellular elements of the adaptive component of immunity, assessment of the severity of autosensitization, assessment of the severity and specificity of atopic hypersensitization, assessment of cytokine status in normal conditions and in response to mitogen. When assessing the phenotypic status of immunoreactivity cells, it turned out that the absolute number of T lymphocytes (CD3+ phenotype), helper T lymphocytes (CD3+CD4+ phenotype) and killer T lymphocytes (CD3+CD8+ phenotype) was significantly reduced in the peripheral blood of test site employees (p ≤ 0.05, compared with similar indicators in the control group). On the contrary, the content of NK cells (CD3-CD56+ phenotype) tended to increase (both the absolute number and the proportion among other lymphocyte populations). Dysfunction of the cellular component of humoral immunoreactivity (a significant decrease in the absolute number of lymphocytes with the CD3-CD20+ phenotype [B lymphocytes] in the peripheral blood), as well as a significant increase in the concentration of serum IgA-class immunoglobulin and pronounced disimmunoglobulinemia in the serum of the examined individuals (compared to individuals in the control group ) indicated a predominantly inhalation method of exposure to immunotoxic industrial toxicants from the landfill on the immune system. Pathogenetically targeted immune-oriented therapy for the personnel of the test site was carried out with drugs that have thymomimetic activity (cytovir-3, thymogen) and are a means of replacement immunocorrection with a cytokine drug (genetically engineered recombinant yeast IL-2 [roncoleukin]). The established effectiveness of the immunotherapy, in particular the reduction in the incidence rate of various nosological forms of immune-related pathology among the site employees who received immunotherapy and the presence of an immunocorrective effect in the immunoactive drugs used for therapy, indicate the advisability of carrying out preventive medical measures in persons professionally exposed to xenobiotic influences as a component of improving medical provision.

Dynamics of clinical and immunological parameters in retinal pigment epithelium transplantation in the context of combined immunosuppressive therapy in the rabbit model of retinal degeneration

Progressive damage of the retinal pigment epithelium (RPE) underlies the pathogenesis of degenerative retinal diseases such as: age-related macular degeneration (AMD), Stargardt’s disease, retinitis pigmentosa, Best’s disease and others. This group of diseases led by AMD leads to irreversible loss of visual functions, blindness and disability. The possibilities of therapy of late stages of AMD are extremely limited. The most promising approach to replace the damaged retinal pigment epithelium appears to be transplantation of RPE cells derived from induced pluripotent stem cells (iPSC-RPE) into the subretinal space (SRS). Despite immune privilege in the SRS, transplantation of xenogeneic cellular material causes severe inflammation in the posterior segment of the eye and leads to graft rejection in an in vivo experiment in the absence of immunosuppression. The solution to the problem of tissue incompatibility in this case can be the use of combined immunosuppressive therapy (CIT), aimed, on the one hand, at suppression of local inflammation (in the eye) and, on the other hand, at suppression of the systemic transplantation immune response. The aim of the study: clinical and immunological analysis of the results of transplantation of IPSC-RPE suspension on the background of CIT, including single intravitreal intraoperative administration of kenalog and further systemic application of mycophenolate mofetil (MMF), in the model of RPE atrophy in rabbits. Standard and specialized ophthalmological examination was performed at early and distant terms after the intervention in order to clinically assess the posttransplantation process. To analyze the immune status, vitreous humor (VH) and blood serum (BS) of rabbits of the experimental groups were collected. The concentrations of TGF-β1, TGF-β2, and IL-2 were determined in the biomaterial using solid-phase enzyme immunoassay. According to the results of the study, subretinal transplantation of IPSC-RPE, performed against the background of combination of single intravitreal intraoperative administration of kenalog and systemic application of MMF, is a safe method, which provides preservation of the retina and other adjacent structures of the eye and allows to prevent rejection of xenogenic material during its transplantation both in a healthy eye and with pre-formed RPE atrophy, which opens perspectives for full testing of biological effects realized by IPSC-RPE.

The paradigm of possibilities leading to the formation of autoimmune and infectious phenotypes of common variable immune deficiency

The term variable in the definition of CVID is associated with the heterogeneity of the genetic nature and clinical manifestation of this variant of PI. Deciphering of the mechanisms or identifying biomarkers of clinical heterogeneity may be important in the timely diagnosis and prognosis of the course of CVID. The purpose of the study was to identify distinctive features in the parameters of the innate and adaptive immune response of the patients with infectious and autoimmune manifestations of CVID in remission and clinical manifestation. Fifteen patients, 11 women and 4 men with an average age 39.7±11.7 years were examined, and they were divided into two subgroups depending on clinical verification: infectious phenotype (10 people) and autoimmune phenotype (5 people). In the absence of clinical signs of activation of autoimmune pathology or exacerbation of chronic infectious processes, peripheral blood monocytes became the application point of distinctive values. An increase in the number of TLR9-expressing monocytes has been shown in patients with autoimmune clinical verification of CVID. The differences in the parameters of the immune status of patients conducted during the period of clinical manifestation consisted of a decrease in the relative content and absolute number of T regulatory lymphocytes, and an increase in the number of monocytes containing TLR9, TLR2 and HLA-DR in patients with an autoimmune phenotype relative to the subgroup with infectious manifestation. The data obtained reflect the involvement of the immunoregulatory potential of the immune system in the clinical manifestation of primary immunodeficiency, even under the conditions of pathogenetic substitution therapy. The evidence of the stated position is a decrease in immunosuppression in autoimmune manifestation due to a decrease in the number of peripheral T-regulatory cells and a smaller proportion of monocyte cells belonging to the M2 suppressive category. Attention is also drawn to the increased potential of primary response to patterns of various nature in autoimmune manifestation due to an increase in the number of monocytes expressing Toll-like receptors of various specificity. The presented results can be proposed as a diagnostic and prognostic indicator of the difference in clinical phenotypes of CVID.

18F]F-AraG Uptake in Vertebral Bone Marrow May Predict Survival in Patients with Non-Small Cell Lung Cancer Treated with Anti-PD-(L)1 Immunotherapy.

Despite the systemic impact of both cancer and the associated immune response, immuno-PET is predominantly centered on assessment of the immune milieu within the tumor microenvironment. The aim of this study was to assess the value of [18F]F-AraG PET imaging as a noninvasive method for evaluation of system-wide immune status of patients with non-small cell lung cancer before starting immunotherapy. Methods: Eleven patients with advanced non-small cell lung cancer were imaged with [18F]F-AraG before starting immunotherapy. Diagnostic [18F]FDG PET/CT scans were analyzed to assess differences in the extent of disease among patients. SUVmax, SUVmean, and total SUV (SUVtotal) from all tumor lesions, active lymph nodes, spleen, vertebral bone marrow, liver, thyroid, heart, and bowel were extracted from the baseline [18F]F-AraG scans, and discriminant and Kaplan-Meier analyses were performed to test their ability to predict patient response and overall survival. Results: The extent of the disease was variable in the patient cohort, but none of the [18F]FDG biomarkers associated with tumor burden (SUVmax, total metabolic tumor volume, and total lesion glycolysis) was predictive of patient survival. The differences in the [18F]F-AraG and [18F]FDG distribution were observed both within and between lesions, confirming that they capture distinct aspects of the tumor microenvironment. Of the 3 SUV parameters studied, [18F]F-AraG SUVtotal provided a dynamic range suitable for stratifying tumors or patients according to their immune activity. [18F]F-AraG SUVtotal measured in the lumbar and sacral vertebrae differentiated between patients who progressed on therapy and those who did not with 90.9% and 81.8% accuracy, respectively. The Kaplan-Meier analysis revealed that patients with high [18F]F-AraG SUVtotal in the lumbar bone marrow had significantly lower probability of survival than those with a low signal (P = 0.0003). Conclusion: This study highlights the significance of assessing systemic immunity and indicates the potential of the [18F]F-AraG bone marrow signal as a predictive imaging biomarker for patient stratification and treatment guidance.

Investigation Role of IL-10 And IL-13 with Some Viral Species in Pathogenesis of Heart Diseases

Background; cardiovascular disease (CVD) is the most common cause of mortality and impairment. Atherosclerosis is the primary underpinning pathophysiology of CVD, but several variables could trigger it. The occurrence of it is linked to multiple risk factors related to metabolism, such as overweight and dyslipidemia. Objective; Detective predictive roles of IL-10 and IL-13 and positivity of viral infections in heart diseases. 60 blood samples were harvested (gel tube) from heart diseases patients who sleeping in hospital after diagnosis them by specialist physician.30 blood samples were taken from healthy individuals that labeled them as a control group. Interleukins (IL-10 and IL-13) and viral species (Parvovirus B19, SARS-CoV-2, HCV and HBV) were calculated by (ELISA). Present outcomes mentioned the most patients were males (71.7%) with age groups 51-60 (26.7%) and 61-70 (33.3%), ex-smokers (65.0%), and lean BMI (63.3%). Our investigation showed Parvovirus B19 scored highest positivity (15.0%), followed by HBV (6.7%), SARS-CoV-2 (5.0%), and then HCV (3.3%) in heart diseases patients with significant difference (p<0.05). Based on interleukins levels, present outcomes showed significant raised levels (p<0.05) of IL-10 and IL-13 in patients than control. ROC curve results showed the IL-13 scored highest sensitivity (80%) and specificity (84%) at cut off (>2.50) compared to IL-10 that showed highest sensitivity (81%) and low specificity (57%) at cut off (>9.50). Conclusions; gender, age and smoking are risk factors for heart diseases. Due to decreased immune state in patients, several viruses were discovered in those patients. IL-10 and IL-13 were raised in patients due to presence inflammation. IL-10 has paradoxical role (pro and anti-inflammatory) in pathogenesis heart diseases . IL-13 is more preferred in diagnosis heart diseases than IL-10 due to has (IL-13) highest sensitivity and specificity. Finally, there is no strong correlation between IL-10 and IL-13 in pathophysiology of heart diseases.

Monitoring Immune Dysfunction in Critically Ill Patients with Carbapenem-Resistant Acinetobacter baumannii Sepsis Treated with Regimens Including Cefiderocol: A Pilot Study to Identify Accessible Biomarkers to Stratify Patients’ Prognosis

Background: Multidrug-resistant Acinetobacter baumannii (CRAB) infections are a serious problem in critical care. This study aims to develop an early prognostic score for immune paralysis, using practical and cost-effective parameters, to predict ICU mortality in patients with CRAB infections being treated with Cefiderocol. Methods: We carried out an observational pilot study on consecutive patients hospitalized in the ICU with ensuing septic Acinetobacter baumannii infections treated with Cefiderocol monotherapy or Cefiderocol including combinations. We investigated the predictive power of lymphocyte counts, lymphocyte subpopulations, serum cholinesterase levels, and reactivation of herpes viruses. Results: Overall, 36 of 39 patients entered in our analysis: 20 survivors and 16 deceased. A total of 12 patients developed bacteremia, 19 patients had HAP/VAP, and 5 patients had a soft tissue infection. Univariate analyses of factors associated with unfavorable outcome revealed a significant association for age (OR: 1.5, CI: 1.11–2.02), SAPS II (OR: 1.05, CI: 1.01–1.1), SOFA score (OR: 1.37, CI: 1.06–1.76), lymphocytopenia (OR: 32.5, CI: 3.45–306.4), viral reactivation (OR: 9.75, CI: 1.72–55.4), and cholinesterase drop <1600 U/L (OR: 39.7, CI: 5.8–271.6). At variance, monotherapy or associations with Cefiderocol were not associated. In the final multivariable model, the only independent predictors of death were age (OR: 1.42, CI: 0.98–2.05), lymphocytopenia (OR: 18.2, CI: 0.87–371), and cholinesterase drop to below 1600 U/L (OR: 9.7, CI: 0.77–123.7). Conclusions: Age, lymphocytopenia, and serum cholinesterase drops, which were nearly significantly associated with an unfavorable outcome, may help pinpoint patients with acute immune paralysis during sepsis. Knowledge of such an immune state may in turn directly influence patients’ care.

Physiological and biochemical assessment of a new three-breed carp cross

The article presents data about the physiological and biochemical assessment of a new three-breed carp cross. The basis for the creation of the cross was the theory of heterosis and the high combinational ability of both parent forms. The effect of heterosis was noted for a number of zootechnical indicators: body weight, head index, number of stamens on the anterior gill arch. The results of a comparative analysis of biochemical parameters such as alanine aminotransferase activity, glucose and total protein content are presented, which allowed us to conclude about the physiological state of the new three-breed cross, about the balance of its carbohydrate metabolism and high rates of protein metabolism, low level of hepatocyte destruction, high immune status and cellular immunity. The new cross is characterized by intensive metabolism of a greater proportion of mature neutrophils and a high level of cellular immunity according to the cytochemical coefficient of lysosomal cationic protein. When obtaining a new three-breed cross, the method of reciprocal hybridization of different carp breeds was used and the choice of an acceptable option with a pronounced effect of heterosis in terms of productivity and vitality was used. The article presents the results of immunological, hematological and biochemical blood tests of the new cross. Also, the article demonstrates the results of studies of the phagocytic activity of neutrophils and determines the content of non-enzymatic cationic protein in them. According to the results of the biochemical assessment, the new three-breed cross showed a high combination of its parent forms with the expected level of the heterosis effect.

Three-dimensional isotropic imaging of live suspension cells enabled by droplet microvortices

Fast, nondestructive three-dimensional (3D) imaging of live suspension cells remains challenging without substrate treatment or fixation, precluding scalable single-cell morphometry with minimal alterations. While optical sectioning techniques achieve 3D live cell imaging, lateral versus depth resolution differences further complicate analysis. We present a scalable microfluidic method capable of 3D fluorescent isotropic imaging of live, nonadherent cells suspended inside picoliter droplets with high-speed single-cell volumetric readout (800 to 1,200 slices in 5 to 8 s) and near-diffraction limit resolution (~216 nm). The platform features a droplet trap array that leverages flow-induced droplet interfacial shear to generate intradroplet microvortices, which rotate single cells on their axis to enable optical projection tomography (OPT)-based imaging. This allows gentle (~1 mPa shear stress) observation of cells encapsulated inside nontoxic isotonic buffer droplets, facilitating scalable OPT acquisition by simultaneous spinning of hundreds of cells. We demonstrate 3D imaging of live myeloid and lymphoid cells in suspension, including K562 cells, as well as naive and activated T cells-small cells prone to movement in their suspended phenotype. Our fully suspended, orientation-independent cell morphometry, driven by isotropic imaging and spherical harmonic analysis, enabled the study of primary T cells across various immunological activation states. This approach unveiled six distinct nuclear content distributions, contrasting with conventional 2D images that typically portray spheroid and bean-like nuclear shapes associated with lymphocytes. Our arrayed-droplet OPT technology is capable of isotropic, single live-cell 3D imaging, with the potential to perform large-scale morphometry of immune cell effector function states while providing compatibility with microfluidic droplet operations.

Integrated transcriptomic analysis reveals dysregulated immune infiltration and pro-inflammatory cytokines in the secretory endometrium of recurrent implantation failure patients

Abstract Recurrent implantation failure (RIF) is a leading impediment to assisted reproductive technology, yet the underlying pathogenesis of RIF remains elusive. Recent studies have sought to uncover novel biomarkers and etiological factors of RIF by profiling transcriptomes of endometrial samples. Nonetheless, the inherent heterogeneity among published studies and a scarcity of experimental validations hinder the identification of robust markers of RIF. Hence, we integrated six publicly accessible datasets with 209 samples, including microarray profiles of endometrial samples in the secretory phase. After removing batch effects, we identified 175 differentially expressed genes. Gene set enrichment analysis identified dysregulation of immunological pathways in RIF. We also observed altered immune infiltration and pro-inflammatory cytokines in RIF. Protein–protein interaction network analysis identified ten hub genes, representing two co-expression modules significantly related to RIF. Knockdown of ENTPD3, one of the hub genes, promoted the epithelial-mesenchymal transition (EMT) process and resulted in elevated levels of pro-inflammatory cytokines. Collectively, our study reveals abnormal gene expressions involving the regulation of EMT and immune status in RIF, providing valuable insights into its pathogenesis.

Identification of a pyroptosis-related long noncoding RNA signature for determining the prognosis and immune status of hepatocellular carcinoma patients.

Despite improvements in cancer screening and diagnosis, hepatocellular carcinoma (HCC) is still diagnosed at an advanced stage, and the prognosis is worse than that of early HCC patients. Therefore, better molecular markers and therapeutic targets in HCC are required. We investigated the predictive value of pyroptosis-related long noncoding RNAs (lncRNAs) in HCC and the effects of these lncRNAs on the immune microenvironment of HCC. RNA sequencing data of HCC patients were extracted from The Cancer Genome Atlas (TCGA) database to identify differentially expressed pyroptosis-related lncRNAs related to overall survival (OS). A model was established to verify the character of pyroptosis-associated lncRNAs in the tumor microenvironment, and their prognostic value was evaluated. A total of 721 PR lncRNAs were identified based on the analysis of the TCGA database. Univariate Cox analysis revealed 37 survival-related PRlncRNAs with prognostic values. As a result of least absolute shrinkage and selection operator (LASSO) regression analysis, 'ELFN-AS1', AC099850.3, AC073389.3, 'HPN-AS1', AC009283.1, and AL139289.1 showed prognostic value. Kaplan-Meier analysis indicated that the OS of the high-risk set was worse than those of the low-risk set in both the training and testing cohorts. Univariate and multivariate analyses revealed that the risk score was a better independent prognostic factor than the stage. The precision of the lncRNA signature was confirmed using receiver operating characteristic curve (ROC) analysis. Immuneand metabolism-related pathways were enriched in both the lowand high-risk groups. Gene set enrichment analysis suggested that the identified lncRNAs regulate HCC tumorigenesis and prognosis by modulating metabolism. Various algorithms were used to confirm the significant differences in immune cells between these 2 groups. These findings could contribute to the development and validation of favorable biomarkers, improve the prognosis and survival of HCC, and help in developed individualized treatment plans for HCC.

Machine learning identification of NK cell immune characteristics in hepatocellular carcinoma based on single-cell sequencing and bulk RNA sequencing.

Hepatocellular carcinoma (HCC) is a highly malignant tumor; however, its immune microenvironment and mechanisms remain elusive. Single-cell sequencing allows for the exploration of immune characteristics within tumor at the cellular level. However, current knowledge regarding the roles of different immune cell populations in liver cancer progression is limited. The main objective of this study is to identify molecular markers with NK cell immune characteristics in hepatocellular carcinoma using various machine learning methods based on Single-Cell Sequencing and Bulk RNA Sequencing. We collected samples from eight normal liver tissues and eight HCC tumor tissues and performed single-cell RNA sequencing for immune cell clustering and expression profile analysis. Using various bioinformatic approaches, we investigated the immune phenotype associated with natural killer (NK) cells expressing high CD7 level. In addition, we verified the role of CD7 in the growth of HCC after NK cell and HCC cells cocultured by RT-qPCR, MTS and Flow cytometer experiments. Finally, we constructed a machine learning model to develop a prognostic prediction system for HCC based on NK cell-related genes. Through single-cell typing, we found that the proportions of hepatocytes and NK cells were significantly elevated in the tumor samples. Moreover, we found that the expression of CD7 was high in HCC and correlated with prognosis. More importantly, Overexpression of CD7 in NK cells significantly inhibited the activity of MHCC97 cells and increased the number of apoptosis of HCC cells (p < 0.05). Furthermore, we observed that NK cells with high CD7 expression were associated with an activated immune phenotype. Our study found that CD7 is an important biomarker for assessing immune status and predicting survival of HCC patients; hence, it is a potential target for immune therapy against HCC.

Characteristics Associated With Measles, Mumps, and Rubella Coverage and Exemptions After a School Immunization Law Change in Washington, 2019-2020.

We aimed to better understand the impact of statewide legislation removing personal belief exemptions (PBEs) for the measles, mumps, and rubella (MMR) school immunization requirement and factors associated with resulting health-seeking behaviors. We used chi-squared tests and logistic regression models to determine individual- and school-level characteristics associated with holding a MMR PBE and with post-law MMR immunization status among students linked to the Washington State Immunization Information System. Of students with a MMR PBE pre-law change, 43.0% completed the MMR vaccine series and 40.4% sought another exemption type. Religious exemptions made up most new MMR exemptions signed (71.8%), followed by medical exemptions (18.5%), and religious membership exemptions (9.7%). Students were more likely to complete the vaccine series post-law change if they attended a school with a low school-level MMR exemption rate, a public school, or held a lower number of school-required immunization exemptions. This study confirms previous concerns that parents might replace their PBE with another exemption type; however, nearly half the students in the cohort completed the MMR vaccine series. Our findings suggest that targeted immunization policies can increase MMR coverage 1-year post-law change but must account for a replacement effect when exemption categories are eliminated.

MANEJO DO HERPES-VÍRUS FELINO: MEDICINA DE ABRIGO

Infection by feline herpesvirus type 1 (FHV-1) is one of the main respiratory diseases in cats, often associated with other pathogens. The virus, which has double-stranded DNA and is sensitive to disinfectants and adverse conditions, proliferates in high-density environments, such as shelters, where stress compromises the immunity of the felines. Transmission mainly occurs through contact with secretions from infected cats, leading to inflammation and cellular necrosis. Clinical symptoms vary depending on the viral load, route of exposure, and the cat's immune status. After an incubation period of 2 to 6 days, symptoms such as depression, sneezing, fever, and loss of appetite appear, followed by nasal and ocular discharge, which may progress to secondary bacterial infection. In severe cases, especially in young or debilitated cats, viral pneumonia may occur. Diagnosis of the feline respiratory complex (FRC) involves clinical and laboratory tests, such as PCR and X-rays, and screening of new cats is fundamental for controlling the infection. Clinical management focuses on stress reduction, hydration, nebulization, and nutritional support. Treatment includes antivirals to reduce viral replication, as well as antibiotics for secondary infections. Vaccination with live attenuated virus, starting at nine weeks of age, is crucial, although it does not provide full protection. Measures such as quarantine, isolation, and disinfection are essential to control the spread of FHV-1. Collaboration between shelters, veterinarians, and animal protection organizations is vital for implementing effective measures and ensuring the welfare of cats, recognizing the importance of early detection and proper management.

Enhanced tumoricidal activity of PD-1 antibody-secreting c-Met CAR-T cells against pancreatic cancer cells

To construct c-Met CAR-T cells secreting PD-1 antibodies to reduce immune inhibitory effect of tumor cells and enhance the efficacy of CAR-T cell therapy against pancreatic cancer. Kaplan-Meier Plotter, GEPIA, and Timer 2.0 bioinformatics databases were used to analyze c-Met expression in pancreatic cancer and its correlation with survival and immune infiltration status. In clinical samples of pancreatic cancer and pancreatic cancer Aspc-1 cells, c-Met and PD-L1 expressions were detected using immunohistochemistry or flow cytometry. Using gene editing technology, PD-1 secretory antibodies and HIS tags were linked to second-generation c-Met CAR molecules to construct PD-1/c-Met CAR plasmids, which were then packaged into lentiviruses for infection of activated T cells. The positive rate and cell subset distribution of CAR-T cells were analyzed with flow cytometry, and secretory PD-1 antibodies in cell supernatants were detected using Western blotting. The target cell killing efficiency and proliferative activity of the modified CAR-T cells were evaluated after activation, and cytokine secretion was analyzed using ELISA. The expression of c-Met was significantly higher in pancreatic cancer than in normal tissues, and its expression level was negatively correlated with the patients' survival and positively correlated with immune cell infiltration. The clinical samples of pancreatic cancer tissues expressed significantly higher levels of c-Met and PD-L1 than the adjacent tissues, and 90.7% and 57.7% of Aspc-1 cells were positive for c-Met and PD-L1, respectively. The constructed PD-1/c-Met CAR-T cells were capable of secreting PD-1 antibodies and showed a significantly higher killing efficiency against tumor cells than c-Met CAR-T cells at an effector-to-target ratio of 20: 1, with also a higher proliferative activity after target cell stimulation and higher levels of IL-2 and TNF-α secretin. PD-1/c-Met CAR-T cells have higher killing efficiency against pancreatic cancer cells with also higher proliferative activity than c-Met CAR-T cells.

Is vaccination against viral hepatitis B safe and immunogenic in patients with rheumatic diseases?

Impressive successes have been achieved in the fight against viral hepatitis B (HBV), but victory over this infection has not yet been achieved. According to various estimates, there are 6–12.5 times more patients with resolved HBV who are carriers of the virus than carriers of the "Australian" surface antigen HBsAg. The basis for the prevention of HBV is passive and active immunization of the population, but the data on the safety and immunogenicity of this vaccine in patients with rheumatic diseases are contradictory. This review examines the safety and immunogenicity of vaccination against hepatitis B virus (HBV) in patients with immune-inflammatory rheumatic diseases. Vaccination against HBV is indicated for patients at risk of infection and should be carried out before starting antirheumatic therapy, as immunogenicity and efficacy are significantly higher in this case. The necessity of a detailed, targeted medical history collection to clarify the risk of HBV infection before prescribing antirheumatic therapy and clarification of the immune status (presence of HBsAg, antibodies against HBc and HBs) before vaccination is emphasized.

Respiratory syncytial virus (RSV) vaccine effectiveness against RSV-associated hospitalisations and emergency department encounters among adults aged 60 years and older in the USA, October, 2023, to March, 2024: a test-negative design analysis

Respiratory syncytial virus vaccines first recommended for use during 2023 were efficacious against lower respiratory tract disease in clinical trials. Limited real-world data regarding respiratory syncytial virus vaccine effectiveness are available. To inform vaccine policy and address gaps in evidence from the clinical trials, we aimed to assess the effectiveness against respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years. We conducted a test-negative design analysis in an electronic health records-based network in eight states in the USA, including hospitalisations and emergency department encounters with respiratory syncytial virus-like illness among adults aged at least 60 years who underwent respiratory syncytial virus testing from Oct 1, 2023, to March 31, 2024. Respiratory syncytial virus vaccination status at the time of the encounter was derived from electronic health record documentation, state and city immunisation registries, and, for some sites, medical claims. Vaccine effectiveness was estimated by immunocompromise status, comparing the odds of vaccination among respiratory syncytial virus-positive case patients and respiratory syncytial virus-negative control patients, and adjusting for age, race and ethnicity, sex, calendar day, social vulnerability index, number of underlying non-respiratory medical conditions, presence of respiratory underlying medical conditions, and geographical region. Among 28 271 hospitalisations for respiratory syncytial virus-like illness among adults aged at least 60 years without immunocompromising conditions, vaccine effectiveness was 80% (95% CI 71-85) against respiratory syncytial virus-associated hospitalisations, and vaccine effectiveness was 81% (52-92) against respiratory syncytial virus-associated critical illness (ICU admission or death, or both). Among 8435 hospitalisations for respiratory syncytial virus-like illness among adults with immunocompromising conditions, vaccine effectiveness was 73% (48-85) against associated hospitalisation. Among 36 521 emergency department encounters for respiratory syncytial virus-like illness among adults aged at least 60 years without an immunocompromising condition, vaccine effectiveness was 77% (70-83) against respiratory syncytial virus-associated emergency department encounters. Vaccine effectiveness estimates were similar by age group and product type. Respiratory syncytial virus vaccination was effective in preventing respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years in the USA during the 2023-24 respiratory syncytial virus season, which was the first season after respiratory syncytial virus vaccine was approved. The Centers for Disease Control and Prevention.

The influence of professional oral hygiene on the indicators of local immunity

Professional oral hygiene is an important part of measures aimed at preventing and maintaining the patient’s health. Local immune response is the first barrier of immune protection capable of preventing infection diseases. The aim of the study - the influence of professional hygiene on the indicators of local immunity has been studied. The study involved two groups of patients: the first group included 19 individuals with chronic caries of varying depths (class I), and the second group comprised 15 individuals with moderate periodontal disease. To evaluate nonspecific oral protection, the index of natural colonization of the buccal epithelium and the activity of microbial adsorption by oral mucosal cells were assessed. Specific immunity was evaluated by measuring the concentration of immunoglobulins in unstimulated saliva. All indicators were recorded both before and after professional oral hygiene procedures. When studying the index of natural colonization of the buccal epithelium, it was found that professional cleaning in both groups led to normalization of the spectrum of bacteria adhered to the epithelium: there was a decrease in the amount of gram-negative microflora, atypical for this biotope, while maintaining a high adhesion index of gram-positive cocci. In persons with caries, before sanation, “unsatisfactory” resistance of oral mucosa was revealed in a third of the examined, after sanation, the number of such patients decreased by 3 times, with “satisfactory” resistance increased by 2 times. In the group with periodontal disease, all patients exhibited “unsatisfactory” mucosal resistance before the hygiene procedures. After sanitation, 20 % “unsatisfactory” resistance persisted. In the majority of patients (80 %), the resistance of the oral mucosa improved to “satisfactory”. The concentration of all classes of immunoglobulins in both groups before sanitation was significantly below the norm, after the measures taken, the indicators increased significantly and reached the level typical for healthy individuals. Carrying out professional cleaning of the teeth leads to the normalization of local immune status even without additional medical immunocorrection.

Access to justice for atrocities in the comparison of land-mark cases on state immunity in Brazil and Italy

ABSTRACT This article investigates differences and similarities in the approach of Italian and Brazilian domestic courts to the topic of access to justice for atrocities and the role of state immunity, taking particular note of the limited and select dialogue between the two judiciaries and reflecting on the potential for further developments of the customary international law rule on state immunity. To do so, the article first outlines the rule on state immunity and offers an overview of the articulated Italian case law on why state immunity cannot bar access to justice for atrocities, considering the judicial developments occurred after 2004. The paper moves on to describe the recent 2021 decision of the Brazilian Supremo Tribunal Federal, in which the Brazil judiciary seemingly joined the Italian trend against state immunity when atrocities are committed. The two different judicial trends are then compared and analysed, with a discussion on the limited explicit reference to Italian decisions by the Supremo Tribunal Federal. The article concludes the research by describing the likely impact of these judicial trends on future developments on the relationship between access to justice for atrocities and state immunity.