The prevalence of bloodborne infections (hepatitis B and C, human immunodeficiency virus) among pediatric patients with oncological and hematological diseases and immunodeficiencies

Patients with oncological and hematological diseases are at high risk of acquiring bloodborne infections due to multiple blood transfusions and frequent parenteral exposure. In order to evaluate the prevalence of bloodborne infections (i. e., hepatitis B, hepatitis C, and human immunodeficiency virus (HIV)), we analyzed data on the seroprevalence of these viruses in patients admitted to the D. Rogachev NMRCPHOI from 2014 to 2020. We also performed a comparative analysis between these data and the prevalence of these infections in the total child population in Russia. The study was approved by the Independent Ethics Committee and the Scientific Council of the D. Rogachev NMRCPHOI. Among patients admitted to the D. Rogachev NMRCPHOI, the mean seroprevalence was 1.7% for hepatitis C, 0.2% for hepatitis B, and 0.1% for HIV. The seroprevalence of hepatitis B and C among our patients was 6 and 50 times higher than the prevalence among Russian children and adolescents, respectively. The prevalence of HIV among patients treated at the D. Rogachev NMRCPHOI was 3 times higher than that among the child and adolescent population in Russia. In patients with oncological and immunological diseases, the detection of HBV DNA, HCV RNA, and Anti-HBc is considered clinically useful and plays an important role in the diagnosis of occult hepatitis infections which cannot be identified with routine diagnostic tests. Our study with pediatric patients with oncological, hematological, and immunological diseases highlights the problem of nosocomial transmission of bloodborne pathogens. HCV transmission in medical facilities is the most pressing issue that requires the implementation of healthcare programs aimed at preventing parenteral transmission and at ensuring the safety of donated blood.

Human Neutrophils Respond to Complement Activation and Inhibition in Microfluidic Devices

Complement activation is key to anti-microbial defenses by directly acting on microbes and indirectly by triggering cellular immune responses. Complement activation may also contribute to the pathogenesis of numerous inflammatory and immunological diseases. Consequently, intense research focuses on developing therapeutics that block pathology-causing complement activation while preserving anti-microbial complement activities. However, the pace of research is slowed down significantly by the limitations of current tools for evaluating complement-targeting therapeutics. Moreover, the effects of potential therapeutic agents on innate immune cells, like neutrophils, are not fully understood. Here, we employ microfluidic assays and measure chemotaxis, phagocytosis, and swarming changes in human neutrophils ex vivo in response to various complement-targeting agents. We show that whereas complement factor 5 (C5) cleavage inhibitor eculizumab blocks all neutrophil anti-microbial functions, newer compounds like the C5 cleavage inhibitor RA101295 and C5a receptor antagonist avacopan inhibit chemotaxis and swarming while preserving neutrophil phagocytosis. These results highlight the utility of microfluidic neutrophil assays in evaluating potential complement-targeting therapeutics.

Missense variants reveal functional insights into the human ARID family of gene regulators

Missense variants are alterations to protein coding sequences that result in amino acid substitutions. They can be deleterious if the amino acid is required for maintaining structure or/and function, but are likely to be tolerated at other sites. Consequently, missense variation within a healthy population can mirror the effects of negative selection on protein structure and function, such that functional sites on proteins are often depleted of missense variants. Advances in high-throughput sequencing have dramatically increased the sample size of available human variation data, allowing for population-wide analysis of selective pressures. In this study, we developed a convenient set of tools, called 1D-to-3D, for visualizing the positions of missense variants on protein sequences and structures. We used these tools to characterize human homologues of the ARID family of gene regulators. ARID family members are implicated in multiple cancer types, developmental disorders, and immunological diseases but current understanding of their mechanistic roles is incomplete. Combined with phylogenetic and structural analyses, our approach allowed us to characterise sites important for protein-protein interactions, histone modification recognition, and DNA binding by the ARID proteins. We find that comparing missense depletion patterns among paralogs can reveal sub-functionalization at the level of domains. We propose that visualizing missense variants and their depletion on structures can serve as a valuable tool for complementing evolutionary and experimental findings.

Phytocompounds and their molecular targets in immunomodulation: a review

Immune cells are important for the healthy function of every organ. The homeostasis of the immune system is selfregulated by T-cells, B-cells, and natural killer cells. The immunomodulation process of immune cells is part of the immunotherapy. According to therapeutic methods of immune responses are categorized as inducing (immunostimulant), amplification (immune booster), attenuation (immunomodulation), and prevention (immunosuppressive) actions. The prevalence of chronic immunological diseases like viral infections, allergies, and cancer is mainly due to the over-activation of the immune system. Further, immunomodulators are reported to manage the severity of chronic immunological disorders. Moreover, these immunomodulator-acting proteins are identified as potential molecular targets for the regulation of the immune system. Moreover, natural compound like phytocompounds are known to bind these targets and modulates the immune system. The specialized phytocompounds like curcumin, quercetin, stilbenes, flavonoids, and lignans are shown the immunomodulatory actions and ameliorate the immunological disorders. The present scenario of a COVID-19 pandemic situation has taught us the need to focus on strengthening the immune system and the development of the most promising immunotherapeutics. This review is focused on an overview of various phytocompounds and their molecular targets for the management of immunological disorders via immunosuppressants and immunostimulants actions.

Unexpected cause of dyspnoea in a patient with allergic rhinitis

A defect in one part of the immune system may affect the whole system. As a result, there may be a myriad of immunological diseases, which are often masked with the one disease that has the most prominent symptoms. This case report presents a patient with long-lasting allergic rhinitis who recently developed dyspnoea in exertion with suspected asthma development. After extensive diagnostic processing, asthma was dismissed, and diagnosis of selective IgA deficiency and coeliac disease with consequential iron deficiency anaemia was established. The patient was treated with parenteral iron and a gluten-free diet, which corrected her anaemia and led to the disappearance of dyspnoea. This paper aims to show the interplay between different immunological disorders and the possible causal connection between them.

A Review on Biosensors and Nanosensors Application in Agroecosystems

Previous decades have witnessed a lot of challenges that have provoked a dire need of ensuring global food security. The process of augmenting food production has made the agricultural ecosystems to face a lot of challenges like the persistence of residual particles of different pesticides, accretion of heavy metals, and contamination with toxic elemental particles which have negatively influenced the agricultural environment. The entry of such toxic elements into the human body via agricultural products engenders numerous health effects such as nerve and bone marrow disorders, metabolic disorders, infertility, disruption of biological functions at the cellular level, and respiratory and immunological diseases. The exigency for monitoring the agroecosystems can be appreciated by contemplating the reported 220,000 annual deaths due to toxic effects of residual pesticidal particles. The present practices employed for monitoring agroecosystems rely on techniques like gas chromatography, high-performance liquid chromatography, mass spectroscopy, etc. which have multiple constraints, being expensive, tedious with cumbersome protocol, demanding sophisticated appliances along with skilled personnel. The past couple of decades have witnessed a great expansion of the science of nanotechnology and this development has largely facilitated the development of modest, quick, and economically viable bio and nanosensors for detecting different entities contaminating the natural agroecosystems with an advantage of being innocuous to human health. The growth of nanotechnology has offered rapid development of bio and nanosensors for the detection of several composites which range from several metal ions, proteins, pesticides, to the detection of complete microorganisms. Therefore, the present review focuses on different bio and nanosensors employed for monitoring agricultural ecosystems and also trying to highlight the factor affecting their implementation from proof-of-concept to the commercialization stage.

SYSTEMIC IMMUNOLOGICAL DISEASES WITH ORAL &MUCOCUTANEOUS MANIFESTATIONS – A FOCUS ON PEMPHIGUS -- AN INSTITUITIONAL STUDY (Preprint)

BACKGROUND Oral mucosal lesions manifest as a first sign of immune mediated disorders. Lichen planus, pemphigus &pemphigoid are the most frequent immunologically mediated mucocutaneous diseases with oral involvement OBJECTIVE A dental surgeon is the first person to come across these lesions that have similar clinical characteristics, therefore their identification based solely on oral lesions is a challenging issue for dentists, leading to a delay in the establishment of a correct diagnosis and suitable management of the patient. METHODS Clinical information was retrieved from records and histopathologic features were reviewed from archives dated 1997 – 2018. ( n = 6300 ). RESULTS Out of 6300 specimens, these immunologically mediated diseases accounted for 105 (1.66%) cases, of which 86 (1.36%) were lichen planus, 4 (0.06%) were pemphigus and 15 (0.23%) were pemphigoid. CONCLUSIONS From the results of this study, it can be inferred that immune-mediated diseases with oral manifestations are comparatively scarce among oral lesions. The present study comprises the retrospective assessment of oral immunologically mediated diseases, in which data regarding the 3 diseases were extracted and analyzed altogether