Subpopulation Level Research Articles

Features of peripheral blood cellular immunity parameters in patients with lung damage up to 30 % in COVID-19

Background. The stability of human organism for different kind of infection, including SARS-CoV-2 is significantly defined by the immune system. The mechanisms of the cellular immunity to the SARS-CoV-2 are not exactly defined and are under study. The aim. To study the features of cell immunity parameters in patients with lung damage up to 30 % in COVID-19. Material and methods. 73 people were examined during the 2020–2021 pandemic. The study group consisted of 31 patients with lung damage up to 30 % with COVID-19, the comparison group consisted of 42 people not infected with SARS-CoV-2. A complete clinical blood count was carried out using a Medonic M20 hematological analyzer (Boule Medical, Sweden), the level of lymphocyte subpopulations was determined using a FACS Calibur cytometer (BD, USA) and FITC- and phycoerythrin-labeled monoclonal antibodies (Sorbent, Russia). Differences were considered statistically significant at p < 0.05. Results. Patients with COVID-19 with lung damage according to computed tomography (CT) ≤ 30 % before the treatment had a restructuring in the ratio of lymphocyte subpopulations in 67.7 % of cases. Lymphopenia (< 1.1 × 109 cells/l) was detected in 34.4 % of patients: a decrease in the absolute count of CD3+ lymphocytes by 30.8 %, CD3+CD4+ – by 35 %, CD3+CD8+ – by 6.7 % (p < 0.05), CD16+CD56+ natural killer (NK) cells – by 29.4 % (p = 0.009). The level of CD95+ lymphocytes in COVID-19 is 3.2 times higher than in healthy individuals. Elevated levels of HLA-DR+- (> 20 %) and CD3+ HLADR+ lymphocytes (> 6 %) are recorded in 60 % and 86.7 % of patients, respectively. Elevated levels of CD19+ B lymphocytes (> 17 %) in COVID-19 are 2.6 times more common than in healthy individuals. Correlation dependences of the count of NK cells with a wide range of T lymphocyte subpopulations were revealed. Conclusion. Cellular immunity indicators in COVID-19 have a number of features that can serve as predictors of the progression of the severity of the disease.

Phytocorrection of Age-Related Changes in the Composition of Blood Plasma, Lymph, and Interstitial Fluid.

We studied the effect of a new complex phytocomposition on age-related changes in the composition of biological fluids (blood, lymph, and interstitial fluid) in old (22-24-month-old) white Sprague-Dawley rats. A 3-month course of phytocomposition induced an increase in the volumes of interstitial fluid (IF) and plasma and stimulated lymph outflow and diuresis. In the blood and lymph, the clotting time increased, while the viscosity and all lipid indicators decreased. The phytocomposition increased the number of erythrocytes and leukocytes, the levels of immunoglobulins (except IgG) and lymphocyte subpopulations, which contributed to correction and improvement of the immune properties of the blood and lymph. Increased hydration of the tissues of the body and strengthening of the anti-atherogenic and immune properties of the lymph and blood led to recovery of the drainage and detoxification function of the lymphatic system. Due to the presence of bioflavonoids, microelements, and vitamins, the new complex phytocomposition produces a lymphotropic effect by changing the composition of the blood, lymph, and IF and stimulates fluid transport from IF into the vascular bed, thereby promoting natural lymph detoxification and increasing the immune properties of the blood and lymph.

Lipid profile after switching from TDF (tenofovir disoproxil)-containing to TAF (tenofovir alafenamide)-containing regimen in virologically suppressed people living with HIV

Background. Tenofovir disoproxil fumarate (TDF) or its prodrug tenofovir alafenamide fumarate (TAF) are currently being recommended in treatment of HIV infection. Distinct pharmacological properties of these two forms of a this drug make TAF treatment less nephrotoxic and lead to better impact on bone density. Nevertheless, there is a rising concern about possible metabolic adverse effects of TAF. The purpose of this study was to evaluate the effects on the lipid profile among ART (antiretroviral therapy)-experienced patients switching from TDF‑containing to TAF‑containing regimen in the first year after the switch. Methods. Demographic and clinical data of HIV‑positive ART‑experienced patients treated in infectious diseases department was retrospectively collected. Changes of lipid profile with regards to baseline BMI, age and time of ART duration were analyzed. Results. In the group of 36 patients there was a significant increase in total cholesterol levels (+18.43 mg/dl, SD = 23.86 mg/dl, p < 0.0001) and LDL levels (+13.75 mg/dl SD = 23.05 mg/dl, p = 0.001) in first 12 months after switching from TDF‑containing to TAF‑containing regimen. There were no statistically significant changes in both HDL and TG levels observed. Analysis of total cholesterol and LDL levels in certain subpopulations revealed a significant increase within first year after the switch in patients younger than 40 years old and in those whose BMI was within normal range. Conclusions. Presented data suggests that switching from TDF to TAF in ART‑experienced patients may be associated with worsening lipid parameters. Early detection and management of dyslipidemias among HIV‑positive patients are needed.

Prediction of outcome using CD14++CD16-, CD14++CD16+ and CD14+CD16++ monocyte subpopulations in patients with complicated intra-abdominal infections.

There is still no study investigating the prognostic performance of CD14++CD16-, CD14++CD16+ and CD14+CD16++ monocyte subpopulations in complicated intra-abdominal infections (cIAIs); therefore, we aimed to evaluate the association between monocyte subtypes and outcome in such patients. A single-center prospective study was conducted at a University Hospital Stara Zagora between November 2018 and August 2021. Preoperatively and on the 3rd postoperative day (POD), we measured the levels of CD14++CD16-, CD14++CD16+ and CD14+CD16++ monocytes in peripheral blood using flow cytometry in 62 patients with cIAIs and 31 healthy controls. Nine of the 62 patients died during hospitalization. Survivors had higher pre-surgery percentages of CD14++CD16- classical monocytes and higher percentage of these cells predicted favorable outcome in ROC analysis (AUROC = 0.781, p = 0.008). The CD14++CD16+ intermediate monocyte percentages were higher in non-survivors both pre- and postoperatively but only the higher preoperative values predicted a lethal outcome (AUROC = 0.722, p = 0.035). For CD14+CD16++ non-classical monocytes, non-survivors had lower percentages on day 3 post-surgery and low percentage was predictive of lethal outcome (AUROC = 0.752, p = 0.046). Perioperative levels of monocyte subpopulations in peripheral blood show a great potential for prognostication of outcome in patients with cIAIs.

Analyzing the Interplay between COVID-19 Viral Load, Inflammatory Markers, and Lymphocyte Subpopulations on the Development of Long COVID.

The global impact of the SARS-CoV-2 infection has been substantial, affecting millions of people. Long COVID, characterized by persistent or recurrent symptoms after acute infection, has been reported in over 40% of patients. Risk factors include age and female gender, and various mechanisms, including chronic inflammation and viral persistence, have been implicated in long COVID's pathogenesis. However, there are scarce studies in which multiple inflammatory markers and viral load are analyzed simultaneously in acute infection to determine how they predict for long COVID at long-term follow-up. This study explores the association between long COVID and inflammatory markers, viral load, and lymphocyte subpopulation during acute infection in hospitalized patients to better understand the risk factors of this disease. This longitudinal retrospective study was conducted in patients hospitalized with COVID-19 in northern Mexico. Inflammatory parameters, viral load, and lymphocyte subpopulation during the acute infection phase were analyzed, and long COVID symptoms were followed up depending on severity and persistence (weekly or monthly) and assessed 1.5 years after the acute infection. This study analyzed 79 patients, among them, 41.8% presented long COVID symptoms, with fatigue being the most common (45.5%). Patients with long COVID had higher lymphocyte levels during hospitalization, and NK cell subpopulation levels were also associated with long COVID. ICU admission during acute COVID-19 was also linked to the development of long COVID symptoms.

Morphological and Trophic Features of the Invasive Babka gymnotrachelus (Gobiidae) in the Plain and Mountainous Ecosystems of the Dniester Basin: Spatiotemporal Expansion and Possible Threats to Native Fishes

Over the last few years, the racer goby B. gymnotrachelus quickly expanded in the mountainous rivers of the Dniester basin at aheight of 300 m a.s.l. and above. The occurrence frequency of the racer goby in fish communities in the mountainous rivers of the Carpathian ecoregion remains low (up to 20%), as compared with the plain rivers, where the species occurs in 70–100% of cases. The major prey groups in its diet in both plain and mountainous were Chironomidae, Diptera, and Crustacea. Chironomidae formed the maximal portion (35% at an occurrence frequency of 72.5%), and Trichoptera formed 18%at an occurrence frequency of 41%, whereas fish larvae were absent in their diet in mountainous rivers. The peculiar environmental conditions of mountainous rivers caused the adaptive modifications of the morphological features of the racer goby at the subpopulation level, which compriseda decrease inthe specimens’ size in rivers with a flow velocity of above 1.5 m/s and rivers with pebble contentsof above 50%in the bottom sediments.The modifications showed an increase inbody streamlining as an adaptation to flow velocity and turbulence and the stony substrate of the river’s bottom. Thus, the morphological adaptation of B. gymnotrachelus to the conditions of the mountainous rivers is in progress, and the formationof astable population in these rivers can be expected. In contrast, the native fish species’ resilience in the face of newcomers is still high, and this is because their alevins are not food for invaders.

A comprehensive study of oxidative stress-related effects on the prognosis and drug therapy of cervical cancer.

Cervical cancer (CC) is a serious global disease with poor prognoses and a significant recurrence rate in patients with advanced disease. Oxidative stress (OS) greatly influences many types of human cancers, making it crucial to understand the functional mechanisms of OS-related genes in CC. The transcriptome and clinical data of three normal samples and 306 patients with CC were obtained from The Cancer Genome Atlas dataset. The GSE44001 dataset was acquired from the Gene Expression Omnibus database. OS-related subtypes in the cohort with CC were identified using unsupervised hierarchical clustering, univariate Cox analysis, gene set enrichment analysis (GSEA), and least absolute shrinkage and selection operator regression analysis. Additionally, molecular pathways that differ across subtypes were determined and OS-related genes linked to the prognosis of patients of CC were determined. Finally, a clinical prognostic gene signature was developed and validated. The relative infiltration level of immune cell subpopulations in different risk groups and subtypes was evaluated using the cell-type identification by estimating relative subsets of RNA transcripts (CIBERPORT) algorithm and single-sample GSEA (ssGSEA) techniques. The present study established two distinct OS subtypes (OS clusters A and B). Analysis using ssGSEA and CIBERSPORT revealed that OS cluster B exhibited a significant level of immune infiltration. A clinical prognostic gene signature was established using OS-related characteristic genes identified by examining the differentially expressed genes across both subtypes. Furthermore, patients with CC were grouped into high- and low-risk groups, with the low-risk group showing higher survival rates. Additionally, these individuals exhibited significant advantages in terms of survival and immunotherapy. Receiver operating characteristic curve analysis demonstrated the higher predictive value of the clinical prognostic gene signature. The outcomes of the validation group depicted congruence with those recorded in the training group. A new model was constructed based on eight OS-related characteristic genes to aid the prediction of the survival rates of individuals with CC. The present study contributes to the existing literature on the mechanisms of OS genes in CC and offers a fresh perspective for future advancements in immunotherapy for such individuals.

Telomerase-independent survival leads to a mosaic of complex subtelomere rearrangements in Chlamydomonas reinhardtii.

Telomeres and subtelomeres, the genomic regions located at chromosome extremities, are essential for genome stability in eukaryotes. In the absence of the canonical maintenance mechanism provided by telomerase, telomere shortening induces genome instability. The landscape of the ensuing genome rearrangements is not accessible by short-read sequencing. Here, we leverage Oxford Nanopore Technologies long-read sequencing to survey the extensive repertoire of genome rearrangements in telomerase mutants of the model green microalga Chlamydomonas reinhardtii In telomerase-mutant strains grown for hundreds of generations, most chromosome extremities were capped by short telomere sequences that were either recruited de novo from other loci or maintained in a telomerase-independent manner. Other extremities did not end with telomeres but only with repeated subtelomeric sequences. The subtelomeric elements, including rDNA, were massively rearranged and involved in breakage-fusion-bridge cycles, translocations, recombinations, and chromosome circularization. These events were established progressively over time and displayed heterogeneity at the subpopulation level. New telomere-capped extremities composed of sequences originating from more internal genomic regions were associated with high DNA methylation, suggesting that de novo heterochromatin formation contributes to the restoration of chromosome end stability in C. reinhardtii The diversity of alternative strategies present in the same organism to maintain chromosome integrity and the variety of rearrangements found in telomerase mutants are remarkable, and illustrate genome plasticity at short timescales.

TLR2 is non-redundant in the population and subpopulation responses to Mycobacterium tuberculosis in macrophages and in vivo.

Tuberculosis (TB), caused by the pathogenic bacterium Mycobacterium tuberculosis (Mtb), is a global health threat. Targeting host pathways that modulate protective or harmful components of inflammation has been proposed as a therapeutic strategy that could aid sterilization or mitigate TB-associated permanent tissue damage. In purified form, many Mtb components can activate innate immune pathways. However, knowledge of the pathways that contribute most to the observed response to live Mtb is incomplete, limiting the possibility of precise intervention. We took a systematic, unbiased approach to define the pathways that drive the earliest immune response to Mtb. Using a macrophage model of infection, we compared the bulk transcriptional response to infection with the response to a panel of Mtb-derived putative innate immune ligands. We identified two axes of response: an NF-kB-dependent response similarly elicited by all Mtb pathogen-associated molecular patterns (PAMPs) and a type I interferon axis unique to cells infected with live Mtb. Consistent with growing literature data pointing to TLR2 as a dominant Mtb-associated PAMP, the TLR2 ligand PIM6 most closely approximated the NF-kB-dependent response to the intact bacterium. Quantitatively, the macrophage response to Mtb was slower and weaker than the response to purified PIM6. On a subpopulation level, the TLR2-dependent response was heterogeneously induced, with only a subset of infected cells expressing key inflammatory genes known to contribute to the control of infection. Despite potential redundancies in Mtb ligand/innate immune receptor interactions during in vivo infection, loss of the TLR2/PIM6 interaction impacted the cellular composition of both the innate and adaptive compartments. IMPORTANCE Tuberculosis (TB) is a leading cause of death globally. Drug resistance is outpacing new antibiotic discovery, and even after successful treatment, individuals are often left with permanent lung damage from the negative consequences of inflammation. Targeting host inflammatory pathways has been proposed as an approach that could either improve sterilization or improve post-treatment lung health. However, our understanding of the inflammatory pathways triggered by Mycobacterium tuberculosis (Mtb) in infected cells and lungs is incomplete, in part because of the complex array of potential molecular interactions between bacterium and host. Here, we take an unbiased approach to identify the pathways most central to the host response to Mtb. We examine how individual pathways are triggered differently by purified Mtb products or infection with the live bacterium and consider how these pathways inform the emergence of subpopulation responses in cell culture and in infected mice. Understanding how individual interactions and immune pathways contribute to inflammation in TB opens the door to the possibility of developing precise therapeutic interventions.

Correlation analysis of parameters of cardiointervalography and immune status in patients with ischemic stroke depending on the affected area (P1-4.007)

<h3>Objective:</h3> To conduct a correlation analysis of cardiointervalography and immunogram parameters in patients with ischemic stroke depending on the location of the ischemia <h3>Background:</h3> The rates of the immunogram and level of autonomic regulation can be used as an additional criterion for autoimmune disorders, assessing the severity of the condition and predicting infectious and inflammatory complications <h3>Design/Methods:</h3> 52 patients with ischemic stroke divided into 3 groups. The I group stroke in the left middle cerebral artery, II–right middle cerebral artery, III-vertebrobasilary basin. Subpopulations of CD3+, CD4+, CD8+, CD16+, CD19+, as well as Interleukin-1β, Interleukin-4, Interleukin-8, Tumor necrosis factor-α were detected in venous blood serum. The functional state of the autonomic nervous system was assessed by R.M. Baevsky’s method of mathematical analysis of heart rate variability. The observation period is 1 and 10 days from the onset of stroke. <h3>Results:</h3> The subpopulation level of lymphocytes depends on the potential of the sympathetic spectrum of vegetal regulation; the indicators of humoral immunity have reciprocal dependencies with neurohumoral activity and parasympathetic regulation. In patients with ischemia in the left hemisphere in the acute period, 21% parameters of cardiointervalography and immunograms show significant correlations; in the acute period, the number of dependencies increased with an increase in sympathetic activity. In patients with stroke in the right hemisphere and in the vertebrobasilar basin in the most acute period, the number of significant correlations was 42%, which is 2 times more than in the first subgroup. In the acute period, with the growth of parasympathetic impact, the relations of the studied parameters reciprocally weaken and decrease. <h3>Conclusions:</h3> An unfavorable prognostic sign in patients with stroke living in low-mountain area is low values of CD3+, CD8+ cells and IL4, high CD16+, CD19+ cells, as well as a low level of neurohumoral and sympathetic regulation <b>Disclosure:</b> Nargiza Chekeeva has nothing to disclose.

Estimating the impact of ship strikes on the Mediterranean fin whale subpopulation

The Mediterranean fin whale (Balaenoptera physalus) subpopulation is under threat from collisions with ships. Given the international dimension of the issue, the French, Italian, Monegasque and Spanish governments have proposed a Particularly Sensitive Sea Area (PSSA), i.e., a management zone of the International Maritime Organization (IMO), in which mandatory and voluntary protective measures can be implemented. Defining the risk and its impact at the subpopulation level is required to improve the chances of an IMO acceptance for such a proposal. While previous research partially succeeded in defining the collision risk, its impact on the subpopulation has not been thoroughly evaluated, especially at the spatial scale of the envisioned PSSA. Our study uses the carcass recovery approach to estimate the number of deadly collisions within the proposed PSSA. We then assess the probability that this number exceeds three management rules: Potential Biological Removal (PBR), Alert Reference Point (ARP) and Critical Reference Point (CRP). These management rules describe thresholds beyond which (a) the incidental mortality may prevent the recovery of the population within 100 years (PBR), (b) there is a cause for concern about incidental mortality (ARP), and (c) there is a critical need to lower the incidental mortality (CRP). We conclude that mortality from collisions alone is in excess of PBR. Taking into account confirmed and suspected collisions in strandings in calculations, the collision mortality exceeds ARP; this threshold being considered unacceptable by some international organisations. Additionally, there is almost a 35% chance that the mortality due to ship strikes exceeds the CRP, likely resulting in a population decline. The probability of anthropogenic mortality exceeding CRP is 60% if we include the fishery-related mortality in stranding (i.e., taking into account the total incidental mortality from bycatch and ship strikes). The PSSA proposal could use our approach to estimate the impact of collisions and assess the effectiveness of implemented protective measures. However, it is important to highlight that the IMO process for establishing a PSSA is lengthy, and our findings show that immediate action is required, as there is a high probability that the ship strike and fishery mortality is beyond the critical threshold fixed by the Agreement on the Conservation of Cetaceans of the Black Sea, Mediterranean Sea and contiguous Atlantic area (ACCOBAMS).

Leveraging Electronic Health Record Data for Timely Chronic Disease Surveillance: The Multi-State EHR-Based Network for Disease Surveillance.

Electronic health record (EHR) data can potentially make chronic disease surveillance more timely, actionable, and sustainable. Although use of EHR data can address numerous limitations of traditional surveillance methods, timely surveillance data with broad population coverage require scalable systems. This report describes implementation, challenges, and lessons learned from the Multi-State EHR-Based Network for Disease Surveillance (MENDS) to help inform how others work with EHR data to develop distributed networks for surveillance. Funded by the Centers for Disease Control and Prevention (CDC), MENDS is a data modernization demonstration project that aims to develop a timely national chronic disease sentinel surveillance system using EHR data. It facilitates partnerships between data contributors (health information exchanges, other data aggregators) and data users (state and local health departments). MENDS uses query and visualization software to track local emerging trends. The program also uses statistical and geospatial methods to generate prevalence estimates of chronic disease risk measures at the national and local levels. Resulting data products are designed to inform public health practice and improve the health of the population. MENDS includes 5 partner sites that leverage EHR data from 91 health system and clinic partners and represents approximately 10 million patients across the United States. Key areas of implementation include governance, partnerships, technical infrastructure and support, chronic disease algorithms and validation, weighting and modeling, and workforce education for public health data users. MENDS presents a scalable distributed network model for implementing national chronic disease surveillance that leverages EHR data. Priorities as MENDS matures include producing prevalence estimates at various geographic and subpopulation levels, developing enhanced data sharing and interoperability capacity using international data standards, scaling the network to improve coverage nationally and among underrepresented geographic areas and subpopulations, and expanding surveillance of additional chronic disease measures and social determinants of health.

Identifying populations at ultra-high risk of suicide using a novel machine learning method

BackgroundTargeted interventions for suicide prevention rely on adequate identification of groups at elevated risk. Several risk factors for suicide are known, but little is known about the interactions between risk factors. Interactions between risk factors may aid in detecting more specific sub-populations at higher risk. MethodsHere, we use a novel machine learning heuristic to detect sub-populations at ultra high-risk for suicide based on interacting risk factors. The data-driven and hypothesis-free model is applied to investigate data covering the entire population of the Netherlands. FindingsWe found three sub-populations with extremely high suicide rates (i.e. >50 suicides per 100,000 person years, compared to 12/100,000 in the general population), namely: (1) people on unfit for work benefits that were never married, (2) males on unfit for work benefits, and (3) those aged 55–69 who live alone, were never married and have a relatively low household income. Additionally, we found two sub-populations where the rate was higher than expected based on individual risk factors alone: widowed males, and people aged 25–39 with a low level of education. InterpretationOur model is effective at finding ultra-high risk groups which can be targeted using sub-population level interventions. Additionally, it is effective at identifying high-risk groups that would not be considered risk groups based on conventional risk factor analysis.

Multilevel assessment of chlorothalonil sediment toxicity to Latin American estuarine biota: Effects on biomarkers, reproduction and survival in different benthic organisms

Chlorothalonil is an organochlorine compound that has long been used in agriculture. In recent years, this compound has been used as an antifouling booster biocide and its presence has been reported in marine coastal environments, especially in navigational areas. Although sediment can be a sink for chlorothalonil due to high affinity to fine particulate matter, toxicity studies with non-target marine and/or estuarine organisms is focused on waterborne exposure only. This study aimed to determine sediment-borne ecotoxicological effects of chlorothalonil on different benthic organisms of the Latin American biota using a integrative multilevel approach. Marine/estuarine organisms were exposed to sediments spiked with chlorothalonil (from 0 to 10.0 μg g−1) and effects at sub-individual (biochemical biomarkers in Anomalocardia flexuosa), individual (lethal effects to Tiburonella viscana and Artemia salina) and subpopulation levels (Nitokra sp. reproduction) were assessed. Increasing chlorothalonil concentrations in sediment caused increasing ecotoxicological effects in different levels of biological organisation, from biochemical to subpopulation levels. The highest exposure concentrations showed increased biomarkers of effects (lipid peroxidation and DNA damage in gills and/or digestive gland of A. flexuosa), lower fecundity and lower survival of the test organisms. GPx activity associated with LPO levels in the digestive gland suggested a response to the oxidant challenge provided by the biocide. At the lowest concentration (0.001 μg g−1), chlorothalonil detoxification mechanisms and defense against its oxidising action, involving GSH and glutathione-dependent enzymes (GST and GPx) were induced. At intermediate concentrations, there was a tendency of decreasing GSH levels, probably due to conjugation with chlorothalonil, which also affected the activities of the glutathione-dependent enzymes. At the highest tested concentration (10.0 μg g−1), chlorothalonil may have restimulated GSH synthesis in the gills of A. flexuosa, although the prooxidant activity has induced effects. This study contributes to assessing the environmental risk of chlorothalonil in sediment for non-target marine and estuarine organisms.

Platelet, Neutrophil and Lymphocyte Quantitative Abnormalities in Patients with Heart Failure: A Retrospective Study.

Heart failure pathophysiology and its clinical symptoms are characterized by inflammation. Elevated levels of leukocyte subpopulations are a well-known indicator of inflammation and play a predictive role in determining the prognosis of patients with cardiovascular diseases. Besides, platelets are essential mediators of inflammation, especially when they interact with leukocytes. Platelet synthesis, activation, and function are all impacted by heart failure. Thus, the study was aimed at determining the magnitude of platelet, neutrophil, and lymphocyte abnormalities in patients with heart failure. A retrospective cross-sectional study was conducted from June to July 2022 at the University of Gondar comprehensive specialized hospital. A total of 245 medical records of heart failure patients were included. Data regarding socio-demographic, clinical, and some hematological and biochemical parameters were collected from medical records. Data was entered into Epi-Data 4.6.0.2 and then exported to Stata 11.0 statistical software for analysis. A binary logistic regression analysis with its odds ratio was calculated to identify factors associated with the outcome variables. P-value <0.05 was considered statistically significant. The most frequent leukocyte abnormality among adults with heart failure was neutrophilia, which was detected in 17.55% (95% CI: 13.26-22.87). Besides, lymphocytosis was observed in 10.20% (95% CI: 6.97-14.70) of patients. The magnitude of thrombocytopenia and thrombocytosis among patients with heart failure was 12.24% (95% CI: 8.67-17.01%) and 2.86% (95% CI: 1.36-5.90%), respectively. Only being female was significantly associated with neutrophilia in patients with heart failure (AOR = 2.33; 95% CI: 1.05-5.16). However, none of the variables were significantly associated with platelet and lymphocyte abnormalities. Neutrophilia, lymphocytosis, and thrombocytopenia are the common leukocyte and platelet abnormalities in heart failure patients. Therefore, early detection and management of the underlying causes of those abnormalities may be important to improve patients' outcomes and prevent further complications.

Salmonella-mediated oral delivery of multiple-target vaccine constructs with conserved and variable regions of SARS-CoV-2 protect against the Delta and Omicron variants in hamster

Since the emergence of the pandemic COVID19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the development of vaccines has been the prime strategy to control the disease transmission. Most of the developed vaccines target the spike protein, however, the emerging variants have alterations, particularly at the same region which may pose resistance to neutralizing antibodies. In this study, we explored the variable and conserved regions of SARS-CoV-2 as a potential inclusion in a multiple-target vaccine with the exploitation of Salmonella-based vector for oral mRNA vaccine against Delta and Omicron variants. Increased IgG and IgA levels imply the induction of humoral response and the CD4+, CD8+ and IFN-γ+ sub-population level exhibits cell-mediated immune responses. The degree of CD44+ cells indicates the induction of memory cells corresponding to long-term immune responses. Furthermore, we assessed the protective efficacy of the vaccines against the Delta and Omicron variants in the hamster model. The vaccine constructs induced neutralizing antibodies and protected the viral-challenged hamsters with significant decrease in lung viral load and reduced histopathological lesions. These results reinforce the use of the conserved and variable regions as potential antigen targets of SARS-CoV-2 as well as the exploitation of bacteria-mediated delivery for oral mRNA vaccine development.

Association of Non-Suicidal Self-Harm with Anxiety, Depression and Aggressive Behavior in Young Men of Military Age

Background: suicidal behavior, intentional self-harm and non-suicidal self-harm are important precursors of suicide in children and adolescents. The objective: to determine the prevalence and structure of non-suicidal self-harm, as well as the relationship of non-suicidal self-harming behavior with aggression, anxiety and depression in a non-clinical group of young men of military age. Participants and methods: the object of the study was 507 young men (from 18 to 27 years old). The average age of the examined was 19.32 years (± 2.35). Assessment of non-suicidal self-harm was carried out using a clinical interview and the scale of self-harming behavior (Polskaya N.A., 2014). The analysis of patterns of aggressive behavior was carried out with the Buss-Perry Aggression Questionnaire (BPAQ) to identify the propensity to aggression, the assessment of anxiety and depression level was assessed on Beck Anxiety and Depression Scales (BAI; BDI). Results: the study showed a high prevalence of non-suicidal selfharm in the non-clinical population of young people (33.9%). Instrumental self-harm was committed at least once in a lifetime by 14.7% of the surveyed, somatic — 19.2%. The most common acts of instrumental self-harm are blows with a fist, foot, head or body body on hard surfaces and cuts with cutting objects. From somatic — biting nails and lips, biting cheeks and tongue, combing the skin and creating obstacles to wound healing were the most frequent. As a result of the correlation analysis of the links of acts of self-harm with the domains of the scale of propensity to aggression from instrumental self-harm, a significant positive correlation was found in relation to self-burns. Punching your body and pulling out your hair turned out to be associated with all domains of the aggression scale. Self-harming was accompanied by depressive symptoms. Symptoms of anxiety correlate with somatic self-harm — punching your body, scratching your skin and biting your cheeks or tongue. Conclusion: non-suicidal self-harm showed positive correlations with manifestations of aggression, anxiety and depression. Effective and evidence-based prevention programs can be implemented at the population, subpopulation and individual levels to timely identify self-harming behavior. At the stage of psychiatric examination of young people, it is advisable to include in the complex of psychodiagnostic methods scales aimed at identifying self-harm, anxiety, depression and aggressive behavior.

Acute exercise mobilizes CD8+ cytotoxic T cells and NK cells in lymphoma patients.

Background: Studies have shown that acute exercise can mobilize several leukocyte subpopulations in healthy individuals. Our aim was to investigate whether a 10-min acute exercise has an effect on immune cell proportions in lymphoma patients. Methods: This study included seven lymphoma patients referred to curative oncologic therapy. Three had Hodgkin and four non-Hodgkin lymphoma, one was female, and their mean age was 51. Patients underwent a 10-min acute exercise on a bicycle ergometer at moderate exercise intensity. Whole blood samples were taken at rest, immediately after exercise, and 30min after exercise. Leukocyte subpopulation levels were determined using flow cytometry. Results: Proportions of total NK cells and CD56+CD16+ NK cells of total leukocytes increased immediately after exercise and decreased back to baseline at 30min post-exercise. Proportion of CD8+ T cells of total T cells increased and proportion of CD4+ T cells of total T cells decreased immediately after exercise, and both returned to baseline at 30min post-exercise. There was no change in the proportions of B cells, granulocytes, or monocytes. Exercising diastolic blood pressure correlated positively with changes in total NK cell and CD56+CD16+ NK cell proportions, and exercising mean arterial pressure correlated positively with change in CD56+CD16+ NK cell proportion. Conclusion: Our findings indicate that a single acute exercise bout of only 10min can cause leukocytosis in lymphoma patients, particularly on cytotoxic T cells and NK cells, which are the most important immune cells fighting against cancer.

Novel insights on the genetic population structure of human-infecting Cyclospora spp. and evidence for rapid subtype selection among isolates from the USA

Human-infecting Cyclospora was recently characterized as three species, two of which (C. cayetanensis and C. ashfordi) are currently responsible for all known human infections in the USA, yet much remains unknown about the genetic structure within these two species. Here, we investigate Cyclospora genotyping data from 2018 through 2022 to ascertain if there are temporal patterns in the genetic structure of Cyclospora parasites that cause infections in US residents from year to year. First, we investigate three levels of genetic characterization: species, subpopulation, and strain, to elucidate annual trends in Cyclospora infections. Next, we determine if shifts in genetic diversity can be linked to any of the eight loci used in our Cyclospora genotyping approach. We observed fluctuations in the abundance of Cyclospora types at the species and subpopulation levels, but no significant temporal trends were identified; however, we found recurrent and sporadic strains within both C. ashfordi and C. cayetanensis. We also uncovered major shifts in the mitochondrial genotypes in both species, where there was a universal increase in abundance of a specific mitochondrial genotype that was relatively abundant in 2018 but reached near fixation (was observed in over 96% of isolates) in C. ashfordi by 2022. Similarly, this allele jumped from 29% to 82% relative abundance of isolates belonging to C. cayetanensis. Overall, our analysis uncovers previously unknown temporal-genetic patterns in US Cyclospora types from 2018 through 2022 and is an important step to presenting a clearer picture of the factors influencing cyclosporiasis outbreaks in the USA.

Comparative Analysis of Tumor-Associated microRNAs and Tetraspanines from Exosomes of Plasma and Ascitic Fluids of Ovarian Cancer Patients.

Ovarian cancer (OC) is one of the most common and fatal types of gynecological cancer. In the early phase of OC detection, the current treatment and diagnostic methods are not efficient and sensitive enough. Therefore, it is crucial to explore the mechanisms of OC metastasis and discover valuable factors for early diagnosis of female cancers and novel therapeutic strategies for metastasis. Exosomes are known to be involved in the development, migration, and invasion of cancer cells, and their cargo could be useful for the non-invasive biopsy development. CD151- and Tspan8-positive exosomes are known to support the degradation of the extracellular matrix, and are involved in stroma remodeling, angiogenesis and cell motility, as well as the association of miR-24 and miR-101 with these processes. The objective of this study was to explore the relationship of these components of exosomal cargo, in patients with OC, to clarify the clinical significance of these markers in liquid biopsies. The levels of tetraspanins Tspan8+ and CD151+ exosomes were significantly higher in plasma exosomes of OC patients compared with healthy females (HFs). The relative levels of miR-24 and miR-101 in plasma exosomes of HFs were significantly higher than in plasma exosomes of OC patients, while the levels of these microRNAs in exosomes from plasma and ascites of ill females showed no difference. Our study revealed a strong direct correlation between the change in the ascites exosomes CD151+Tspan8+ subpopulation level and the expression levels of the ascites (R = 0.81, p < 0.05) and plasma exosomal miR-24 (R = 0.74, p < 0.05) in OC patients, which confirms the assumption that exosomal cargo act synergistically to increase cellular motility, affecting cellular processes and signaling. Bioinformatics analysis confirmed the involvement of CD151 and Tspan8 tetraspanins and genes controlled by miR-24-3p and miR-101 in signaling pathways, which are crucial for carcinogenesis, demonstrating that these tetraspanins and microRNAs are potential biomarkers for OC screening, and predictors of poor clinicopathological behavior in tumors.