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Background: Given the rising interest in complementary therapeutic strategies for autism spectrum disorder (ASD), this research aims to provide a comprehensive analysis of the impact of animal-assisted activities and therapies (AAAT) on various ASD symptoms., Methods: A meticulous search of databases, including Scopus and PubMed, was conducted to gather relevant research on AAAT for ASD. This process led to the selection of 45 studies encompassing 1,212 participants. The chosen studies were then subjected to a meta-analysis to evaluate the efficacy of AAAT in alleviating core ASD symptoms., Results: The meta-analysis revealed significant improvements in several core ASD symptoms due to AAAT. Notably, there were improvements in social communication (MD = -4.96, 95% CI [-7.49, -2.44]), irritability (MD = -2.38, 95% CI [-4.06, -0.71]), hyperactivity (MD = -4.03, 95% CI [-6.17, -1.89]), and different word usage skills (MD = 20.48, 95% CI [7.41, 33.55]). However, social awareness (MD = -1.63, 95% CI [-4.07, 0.81]), social cognition (MD = -3.60, 95% CI [-9.36, 2.17]), social mannerisms (MD = -0.73, 95% CI [-2.55, 1.09]), social motivation (MD = -1.21, 95% CI [-2.56, 0.13]), lethargy (MD = -1.12, 95% CI [-3.92, 1.68]), and stereotypical behaviors (MD = -0.23, 95% CI [-1.27, 0.80]) did not significantly improve., Conclusion: The study demonstrates the potential of AAAT in improving certain core symptoms of ASD, such as social communication, irritability, hyperactivity, and word usage skills. However, the effectiveness of AAAT in other ASD symptom domains remains uncertain. The research is limited by the absence of long-term follow-up data and a high risk of bias in existing studies. Therefore, while the findings indicate the promise of AAAT in specific areas, caution is advised in generalizing its efficacy across all ASD symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xiao, Bagayi, Yang, Huang, Zhong, Kiselev, Bolkov, Tuzankina and Chereshnev.)

Background: Inborn Errors of Immunity (IEI) are characterized by a heightened susceptibility to infections, allergies, and various other health complications. Health-Related Quality of Life (HRQOL) in patients with IEI is a critical area of research that demands attention due to the impact of IEI on patients' lives. This study utilized bibliometric methods, aiming to comprehensively explore the research content and hotspots in the field of HRQOL in patients with IEI., Methods: This bibliometric analysis utilized data from the Science Citation Index Expanded (SCIE) and Social Sciences Citation Index (SSCI) within the Web of Science core datasets up to January 1, 2024. The study focused on literature that addressed HRQOL in IEI patients, involving a total of 1,807 authors and 309 articles published across 112 journals. The analysis included publication volume and growth trends, country and institutional contributions, authorship, and journal analysis., Results: The research found that despite the importance of HRQOL in IEI, the volume of publications in this field remains consistently low, with no significant increase in trend. The USA leads in publication and citation volumes, reflecting a geographical imbalance in research contributions. Key journals in this field include the Journal of Clinical Immunology, Frontiers in Immunology, and the Journal of Allergy and Clinical Immunology. The study highlights that while treatments like hematopoietic stem cell transplants and gene therapy have improved patient IEI survival rates, they still often come with significant side effects impacting HRQOL. The analysis underlines the need for comprehensive HRQOL assessments in IEI, considering the physical and psychological impacts of treatments., Conclusions: This study represents a bibliometric analysis focusing on HRQOL in patients with. It underscores the need for more extensive and systematic research in this area, emphasizing the importance of a multidisciplinary approach. Despite advancements in medical treatments for IEI, there is a crucial need to focus on HRQOL to enhance patient satisfaction and overall well-being. The findings advocate for more personalized treatment plans and a better understanding of the psychosocial needs of patients with IEI to improve their quality of life., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xiao, Huang, Zang, Kiselev, Bolkov, Tuzankina and Chereshnev.)

Single-nucleotide polymorphisms in the ELANE (Elastase, Neutrophil Expressed) gene are associated with severe congenital neutropenia, while the ELANE gene provides instructions for making a protein called neutrophil elastase. We identified disease susceptibility single-nucleotide polymorphisms (SNPs) in the ELANE gene using several computational tools. We used cutting-edge computational techniques to investigate the effects of ELANE mutations on the sequence and structure of the protein. Our study suggested that eight nsSNPs (rs28931611, rs57246956, rs137854448, rs193141883, rs201723157, rs201139487, rs137854451, and rs200384291) are the most deleterious in ELANE gene and disturb protein structure and function. The mutants F218L, R34W, G203S, R193W, and T175M have not yet been identified in patients suffering from SCN and cyclic hematopoiesis, while C71Y, P139R, C151Y, G214R, and G203C reported in our study are already associated with both of the disorders. These mutations are shown to destabilize structure and disrupt ELANE protein activation, splicing, and folding and might diminish trypsin-like serine protease efficiency. Prediction of posttranslation modifications highlighted the significance of deleterious nsSNPs because some of nsSNPs affect potential phosphorylation sites. Gene-gene interactions showed the relation of ELANE with other genes depicting its importance in numerous pathways and coexpressions. We identified the deleterious nsSNPs, constructed mutant protein structures, and evaluated the impact of mutation by employing molecular docking. This research sheds light on how ELANE failure upon mutation results in disease progression, including congenital neutropenia, and validation of these novel predicted nsSNPs is required through the wet lab., Competing Interests: The authors do not have any conflicts of interest., (Copyright © 2022 Khyber Shinwari et al.)

T Cell Immune Regulator 1, ATPase H + Transporting V0 Subunit A3 (TCIRG1 gene provides instructions for making one part, the a3 subunit, of a large protein complex known as a vacuolar H + -ATPase (V-ATPase). V-ATPases are a group of similar complexes that act as pumps to move positively charged hydrogen atoms (protons) across membranes. Single amino acid changes in highly conserved areas of the TCIRG1 protein have been linked to autosomal recessive osteopetrosis and severe congenital neutropenia. We used multiple computational approaches to classify disease-prone single nucleotide polymorphisms (SNPs) in TCIRG1. We used molecular dynamics analysis to identify the deleterious nsSNPs, build mutant protein structures, and assess the impact of mutation. Our results show that fifteen nsSNPs (rs199902030, rs200149541, rs372499913, rs267605221, rs374941368, rs375717418, rs80008675, rs149792489, rs116675104, rs121908250, rs121908251, rs121908251, rs149792489 and rs116675104) variants are likely to be highly deleterious mutations as by incorporating them into wild protein they destabilize the wild protein structure and function. They are also located in the V-ATPase I domain, which may destabilize the structure and impair TCIRG1 protein activation, as well as reduce its ATPase effectiveness. These mutants have not yet been identified in patients suffering from CN and osteopetrosis while (G405R, R444L, and D517N) reported in our study are already associated with osteopetrosis. Mutation V52L reported in our study was identified in a patient suspected for CN. Finally, these mutants can help to further understand the broad pool of illness susceptibilities associated with TCIRG1 catalytic kinase domain activation and aid in the development of an effective treatment for associated diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shinwari, Rehman, Liu, Bolkov, Tuzankina and Chereshnev.)

Inborn errors of immunity can be detected by evaluating circular DNA (cDNA) fragments of T- and B-cell receptors (TREC and KREC) resulting from the receptor gene rearrangement in T and B cells. Maturation and activation of the fetal immune system is known to proceed gradually according to the gestational age, which highlights the importance of the immune status in premature infants at different gestational ages. In this article, we evaluated TREC and KREC levels in infants of various gestational ages by real-time PCR with taking into account the newborn's weight and sex. The 95% confidence intervals for TREC and KREC levels (expressed in the number of cDNA copies per 105 cells) were established for different gestational groups. The importance of studying immune system development in newborns is informed by the discovered dependence of the level of naive markers on the gestational stage in the early neonatal period., (Copyright ® 2022 National Research University Higher School of Economics.)

Background: Immunotherapies including PD-1/PD-L1 antibodies have been approved for the treatment of Muscle-invasive Bladder Cancer (MIBC) patients. However, immunotherapies could only be beneficial for about 20% MIBC patients. Thus, identification of the immune subtype is becoming increasingly important. This study aimed to explore the immune subtype by analyzing the gene expression profiles., Methods: A total of 6 datasets including (GSE13507, GSE31684, GSE32548, GSE32894, GSE69795, and TCGA-BLCA) were downloaded. The gene expression profiles from different datasets were combined since the batch effects were removed. We performed unsupervised clustering analysis to identify the immune subtype by the combined gene expression profiles. The tumor-infiltration levels of 22 immune cells, immune scores, and tumor purity were calculated, and the survival analysis was performed to investigate the prognosis difference between immune subtypes. The enriched pathways for each immune subtype were obtained., Results: We identified four novel immune subtypes (referred to S1, S2, S3, and S4) among MIBC patients. We found that S1 was enriched in immune scores had the best prognosis. In contrast, S3 was poor in immune scores and had the worst prognosis. Subtype S1, S2, S3, and S4 were enriched in immune-related pathways, extracellular matrix-related pathways, metabolism-related pathways, and cancer-related pathways, respectively., Conclusion: The current study suggests that the immune subtypes based on gene expression profiles could contribute to select the appropriate MIBC patient for immunotherapies.

Hennekam lymphangiectasia-lymphedema syndrome has been linked to single-nucleotide polymorphisms in the CCBE1 (collagen and calcium-binding EGF domains 1) gene. Several bioinformatics methods were used to find the most dangerous nsSNPs that could affect CCBE1 structure and function. Using state-of-the-art in silico tools, this study examined the most pathogenic nonsynonymous single-nucleotide polymorphisms (nsSNPs) that disrupt the CCBE1 protein and extracellular matrix remodeling and migration. Our results indicate that seven nsSNPs, rs115982879, rs149792489, rs374941368, rs121908254, rs149531418, rs121908251, and rs372499913, are deleterious in the CCBE1 gene, four (G330E, C102S, C174R, and G107D) of which are the highly deleterious, two of them (G330E and G107D) have never been seen reported in the context of Hennekam syndrome. Twelve missense SNPs, rs199902030, rs267605221, rs37517418, rs80008675, rs116596858, rs116675104, rs121908252, rs147974432, rs147681552, rs192224843, rs139059968, and rs148498685, are found to revert into stop codons. Structural homology-based methods and sequence homology-based tools revealed that 8.8% of the nsSNPs are pathogenic. SIFT, PolyPhen2, M-CAP, CADD, FATHMM-MKL, DANN, PANTHER, Mutation Taster, LRT, and SNAP2 had a significant score for identifying deleterious nsSNPs. The importance of rs374941368 and rs200149541 in the prediction of post-translation changes was highlighted because it impacts a possible phosphorylation site. Gene-gene interactions revealed CCBE1's association with other genes, showing its role in a number of pathways and coexpressions. The top 16 deleterious nsSNPs found in this research should be investigated further in the future while researching diseases caused CCBE1 gene specifically HS. The FT web server predicted amino acid residues involved in the ligand-binding site of the CCBE1 protein, and two of the substitutions (R167W and T153N) were found to be involved. These highly deleterious nsSNPs can be used as marker pathogenic variants in the mutational diagnosis of the HS syndrome, and this research also offers potential insights that will aid in the development of precision medicines. CCBE1 proteins from Hennekam syndrome patients should be tested in animal models for this purpose., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Khyber Shinwari et al.)

Nijmegen breakage syndrome (NBS) is a DNA repair disorder characterized by combined immunodeficiency and a high predisposition to lymphoid malignancies. The majority of NBS patients are identified with a homozygous five base pair deletion in the Nibrin ( NBN) gene (c.657_661del5, p.K219fsX19) with a founder effect observed in Caucasian European populations, especially of Slavic origin. We present here an analysis of a cohort of 136 NBS patients of Eastern Slav origin across Belarus, Ukraine, Russia, and Latvia with a focus on understanding the geographic distribution, incidence of malignancy, and treatment outcomes of this cohort. Our analysis shows that Belarus had the highest prevalence of NBS (2.3 per 1,000,000), followed by Ukraine (1.3 per 1,000,000), and Russia (0.7 per 1,000,000). Of note, the highest concentration of NBS cases was observed in the western regions of Belarus and Ukraine, where NBS prevalence exceeds 20 cases per 1,000,000 people, suggesting the presence of an "Eastern Slavic NBS hot spot." The median age at diagnosis of this cohort ranged from 4 to 5 years, and delay in diagnosis was more pervasive in smaller cities and rural regions. A total of 62 (45%) patients developed malignancies, more commonly in males than females (55.2 vs. 34.2%; p =0.017). In 27 patients, NBS was diagnosed following the onset of malignancies (mean age: 8 years). Malignancies were mostly of lymphoid origin and predominantly non-Hodgkin lymphoma (NHL) ( n =42, 68%); 38% of patients had diffuse large B-cell lymphoma. The 20-year overall survival rate of patients with malignancy was 24%. However, females with cancer experienced poorer event-free survival rates than males (16.6% vs. 46.8%, p =0.036). Of 136 NBS patients, 13 underwent hematopoietic stem cell transplantation (HSCT) with an overall survival of 3.5 years following treatment (range: 1 to 14 years). Indications for HSCT included malignancy ( n =7) and immunodeficiency ( n =6). Overall, 9% of patients in this cohort reached adulthood. Adult survivors reported diminished quality of life with significant physical and cognitive impairments. Our study highlights the need to improve timely diagnosis and clinical management of NBS among Eastern Slavs. Genetic counseling and screening should be offered to individuals with a family history of NBS, especially in hot spot regions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sharapova, Pashchenko, Bondarenko, Vakhlyarskaya, Prokofjeva, Fedorova, Savchak, Mareika, Valiev, Popa, Tuzankina, Vlasova, Sakovich, Polyakova, Rumiantseva, Naumchik, Kulyova, Aleshkevich, Golovataya, Minakovskaya, Belevtsev, Latysheva, Latysheva, Beznoshchenko, Akopyan, Makukh, Kozlova, Varabyou, Ballow, Ong, Walter, Kondratenko, Kostyuchenko and Aleinikova.)

Immunotherapy, especially anti-PD-1, is becoming a pillar of modern muscle-invasive bladder cancer (MIBC) treatment. However, the objective response rates (ORR) are relatively low due to the lack of precise biomarkers to select patients. Herein, the molecular subtype, tumor mutation burden (TMB), and CD8+ T cells were calculated by the gene expression and mutation profiles of MIBC patients. MIBC immunotypes were constructed using clustering analysis based on tumor mutation burden, CD8+ T cells, and molecular subtypes. Mutated genes, enriched functional KEGG pathways and GO terms, and co-expressed network-specific hub genes have been identified. We demonstrated that ORR of immunotype A patients identified by molecular subtype, CD8+ T cells, and TMB is about 36% predictable. PIK3CA, RB1, FGFR3, KMT2C, MACF1, RYR2, and EP300 are differentially mutated among three immunotypes. Pathways such as ECM-receptor interaction, PI3K-Akt signaling pathway, and TGF-beta signaling pathway are top-ranked in enrichment analysis. Low expression of ACTA2 was associated with the MIBC survival benefit. The current study constructs a model that could identify suitable MIBC patients for immunotherapy, and it is an important step forward to the personalized treatment of bladder cancers.

Introduction: Newborn screening (NBS) by quantifying T cell receptor excision circles (TRECs) and Kappa receptor excision circles in neonatal dried blood spots (DBS) enables early diagnosis of different types of primary immune deficiencies. Global newborn screening for PID, using an assay to detect T-cell receptor excision circles (TREC) in dried blood spots (DBS), is now being performed in all states in the United States. In this review, we discuss the development and outcomes of TREC, TREC/KREC combines screening, and continued challenges to implementation., Objective: To review the diagnostic performance of published articles for TREC and TREC/ KREC based NBS for PID and its different types., Methods: Different research resources were used to get an approach for the published data of TREС and KREC based NBS for PID like PubMed, Scopus, Google Scholar, Research gate EMBASE. We extracted TREC and KREC screening Publisher with years of publication, content and cut-off values, and a number of retests, repeat DBS, and referrals from the different published pilot, pilot cohort, Case series, and cohort studies., Results: We included the results of TREC, combined TREC/KREC system based NBS screening from different research articles, and divided these results between the Pilot studies, case series, and cohort. For each of these studies, different parameter data are excluded from different articles. Thirteen studies were included, re-confirming 89 known SCID cases in case series and reporting 53 new SCID cases in 3.15 million newborns. Individual TREC contents in all SCID patients were <25 TRECs/μl (except in those evaluated with the New York State assay)., Conclusion: TREC and KREC sensitivity for typical SCID and other types of PID was 100 %. It shows its importance and anticipating the significance of implementation in different undeveloped and developed countries in the NBS program in upcoming years. Data adapting the screening algorithm for pre-term/ill infants reduce the amount of false-positive test results., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Primary immunodeficiencies (PID) are a group of rare genetic disorders with a multitude of clinical symptoms. Characterization of epidemiological and clinical data via national registries has proven to be a valuable tool of studying these diseases. Materials and Methods: The Russian PID registry was set up in 2017, by the National Association of Experts in PID (NAEPID). It is a secure, internet-based database that includes detailed clinical, laboratory, and therapeutic data on PID patients of all ages. Results: The registry contained information on 2,728 patients (60% males, 40% females), from all Federal Districts of the Russian Federation. 1,851/2,728 (68%) were alive, 1,426/1,851 (77%) were children and 425/1,851 (23%) were adults. PID was diagnosed before the age of 18 in 2,192 patients (88%). Antibody defects (699; 26%) and syndromic PID (591; 22%) were the most common groups of PID. The minimum overall PID prevalence in the Russian population was 1.3:100,000 people; the estimated PID birth rate is 5.7 per 100,000 live births. The number of newly diagnosed patients per year increased dramatically, reaching the maximum of 331 patients in 2018. The overall mortality rate was 9.8%. Genetic testing has been performed in 1,740 patients and genetic defects were identified in 1,344 of them (77.2%). The median diagnostic delay was 2 years; this varied from 4 months to 11 years, depending on the PID category. The shortest time to diagnosis was noted in the combined PIDs-in WAS, DGS, and CGD. The longest delay was observed in AT, NBS, and in the most prevalent adult PID: HAE and CVID. Of the patients, 1,622 had symptomatic treatment information: 843 (52%) received IG treatment, mainly IVIG (96%), and 414 (25%) patients were treated with biological drugs. HSCT has been performed in 342/2,728 (16%) patients, of whom 67% are currently alive, 17% deceased, and 16% lost to follow-up. Three patients underwent gene therapy for WAS; all are currently alive. Conclusions: Here, we describe our first analysis of the epidemiological features of PID in Russia, allowing us to highlight the main challenges around PID diagnosis and treatment., (Copyright © 2020 Mukhina, Kuzmenko, Rodina, Kondratenko, Bologov, Latysheva, Prodeus, Pampura, Balashov, Ilyina, Latysheva, Deordieva, Shvets, Deripapa, Abramova, Pashenko, Vahlyarskaya, Zinovyeva, Zimin, Skorobogatova, Machneva, Fomina, Ipatova, Barycheva, Khachirova, Tuzankina, Bolkov, Shakhova, Kamaltynova, Sibgatullina, Guseva, Kuznetsova, Milichkina, Totolian, Kalinina, Goltsman, Sulima, Kutlyanceva, Moiseeva, Khoreva, Nesterenko, Tymofeeva, Ermakova, Proligina, Kalmetieva, Davletbaieva, Mirsayapova, Richkova, Kuzmicheva, Grakhova, Yudina, Orlova, Selezneva, Piskunova, Samofalova, Bukina, Pechkurova, Migacheva, Zhestkov, Barmina, Parfenova, Isakova, Averina, Sazonova, Starikova, Shilova, Asekretova, Suprun, Kleshchenko, Lebedev, Demikhova, Demikhov, Kalinkina, Gorenkova, Duryagina, Pavlova, Shinkareva, Smoleva, Aleksandrova, Bambaeva, Philippova, Gracheva, Tcyvkina, Efremenkov, Mashkovskaya, Yarovaya, Alekseenko, Fisyun, Molokova, Troitskya, Piatkina, Vlasova, Ukhanova, Chernishova, Vasilieva, Laba, Volodina, Safonova, Voronin, Gurkina, Rumyantsev, Novichkova and Shcherbina.)

Background: Urothelial bladder cancer (BLCA) is one of the most common internal malignancies worldwide with poor prognosis. This study aims to explore effective prognostic biomarkers and construct a prognostic risk score model for patients with BLCA., Methods: Weighted gene co-expression network analysis (WGCNA) was used for identifying the co-expression module related to the pathological stage of BLCA based on the RNA-Seq data retrieved from The Cancer Genome Atlas database. Prognostic biomarkers screened by Cox proportional hazard regression model and random forest were used to construct a risk score model that can predict the prognosis of patients with BLCA. The GSE13507 dataset was used as the independent testing dataset to test the performance of the risk score model in predicting the prognosis of patients with BLCA., Results: WGCNA identified seven co-expression modules, in which the brown module consisted of 77 genes was most significantly correlated with the pathological stage of BLCA. Cox proportional hazard regression model and random forest identified TPST1 and P3H4 as prognostic biomarkers. Elevated TPST1 and P3H4 expressions were associated with the high pathological stage and worse survival. The risk score model based on the expression level of TPST1 and P3H4 outperformed pathological stage indicators and previously proposed prognostic models., Conclusion: The gene co-expression network-based study could provide additional insight into the tumorigenesis and progression of BLCA, and our proposed risk score model may aid physicians in the assessment of the prognosis of patients with BLCA., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Basal and luminal subtypes of muscle-invasive bladder cancer (MIBC) have distinct molecular profiles and heterogeneous clinical behaviors. The interactions between mRNAs and lncRNAs, which might be regulated by miRNAs, have crucial roles in many cancers. However, the miRNA-dependent crosstalk between lncRNA and mRNA in specific MIBC subtypes still remains unclear. In this study, we first classified MIBC into two conservative subtypes using miRNA, mRNA and lncRNA expression data derived from The Cancer Genome Atlas. Then we investigated subtype-related biological pathways and evaluated the subtype classification performance using Decision Trees, Random Forest and eXtreme Gradient Boosting (XGBoost). At last, we explored potential miRNA-mediated lncRNA-mRNA crosstalks based on co-expression analysis. Our results show that: (1) the luminal subtype is primarily characterized by upregulation of metabolism-related pathways while the basal subtype is predominantly characterized by upregulation of epithelial-mesenchymal transition, metastasis, and immune system process-related pathways; (2) the XGBoost prediction model is consistently robust for classification of the molecular subtypes of MIBC across four datasets (The area under the ROC curve > 0.9); (3) the expression levels of the molecules in the miR-200c and miR141-mediated lncRNA-mRNA crosstalks differ considerably between the two subtypes and have close relationships with the prognosis of MIBC. The miR-200c and miR-141-dependent mRNA-lncRNA crosstalks might be of great significance in tumorigenesis and tumor progression and may serve as the novel prognostic predictors and classification markers of MIBC subtypes.

Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame.

Aim: Search of association of polymorphisms in DEFB1, IL-10, TNF-α and TLR2 genes with development of chronic generalized periodontitis in representatives of Ural region (Caucasian race)., Materials and Methods: 142 patients, that were split into 3 groups, took part in the study: a group of patients with periodontitis, a group with frequent inflammatory disease of upper respiratory tract and a comparison group--healthy donors. A study of polymorphic markers was carried out: DEFB1 (-44G/C), DEFB1 (-20A/G), IL-10 (-1082.A/G), TNF-α (-308 G/A), Arg753Gln and Arg677Trp using PCR in real time mode., Results: Association of infectious pathology ofupper respiratory tract and development of periodontitis diseases with markers in DEFB1 (-44G/C) and Arg753Gln and Arg677Trp genes was determined. Significant differences in distribution of genotypes and alleles of genes IL-10 and TNF-α in the group of patients with periodontitis and comparison group were not detected., Conclusion: DEFB1 (-44G/C) polymorphism can be examined as a marker of periodontitis development risk.

Acute respiratory infections (ARI) still represent a big challenge for paediatricians, especially in those children defined as "ailed" as they are more susceptible to such kinds of disease. In this paediatric population, the immune system is still under-developed with an evident alteration in cytokine levels. A clinical study was carried out in 5 sites in Russia with the intention to enroll children particularly susceptible to contract respiratory infections (defined as "ailing"), assigning them to a treatment group with pidotimod in comparison with a control group, treating them for 30 days and observing the reduction in the number of ARI episodes throughout the follow-up period (6 months). Moreover, changes in serum immunological markers were evaluated at baseline and 30 days after treatment discontinuation. One hundred and fifty-seven ailing children were enrolled and assigned to two arms: a main pidotimod treatment group or a control group. The percentage of incidence of ARIs in the observation period at three different time points was statistically significant (p < 0.05). At the end of the follow-up period (after 6 months), ARIs had developed in 72 children (92.3%) in the main group and in 79 patients (100%) in the control group. Concerning changes of the immunological markers, the treatment group showed a better profile of normalization compared to the control group. The 30-day pidotimod therapy course led to improvement/reduction in the rate of acute respiratory infection recurrence in ailing children within a 3-month period, with a quick elimination of symptoms and signs of infection and, as a result, a faster recovery. The normalisation of the content of the pro-inflammatory cytokine interleukin-8 confirmed the immune-modulatory effect of the investigational drug, underlying its prophylactic effect.

Dissemination of infectious inflammation was studied in experimental influenza and acute and chronic herpesvirus infections. The possibility of articular involvement into the infectious process was evaluated. Pathomorphological signs of changes in the articular tissue confirmed the effects of these viruses on the locomotor pathology. Results of virus infection simulation in experimental animals suggest this model for studies of the pathogenesis of diseases of viral etiology (including those with articular involvement) in humans.

The concentrations of allergen-specific IgE were measured in 146 children with respiratory, skin, and mixed forms of allergic diseases. The spectrum of the allergens was determined and specific features for each of the studied patient populations defined.