Differential Inflammatory Responses in Adult and Pediatric COVID-19 Patients: Implications for Long-Term Consequences and Anti-Inflammatory Treatment.

BACKGROUND COVID-19 manifests with varying degrees of severity across different age groups; adults typically experience more severe symptoms than children. Matrix metalloproteinases (MMPs), known for their role in tissue remodeling and immune responses, may contribute to the pathophysiological disparities observed between these groups. We sought to delineate differences in serum MMP profiles between adult and pediatric COVID-19 patients, assess the influence of anti-inflammatory treatment on MMP levels, and examine potential implications for long-term consequences. MATERIAL AND METHODS Serum samples from adult and pediatric COVID-19 patients, alongside controls, were analyzed for MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12, MMP-13, EMMPRIN, TNF-alpha, TIMP-1, TIMP-2, TIMP-3, and TIMP-4. A subset of adult patients received treatment with glucocorticoids, tocilizumab, and convalescent plasma, and MMP levels were compared with those of untreated patients. RESULTS Elevated levels of MMP-1, MMP-7, TIMP-1, and TIMP-2 were observed in adult and pediatric patients. Adult patients displayed higher concentrations of MMP-3, MMP-8, MMP-9, TNF-alpha, and TIMP-4 than children. Post-treatment reduction in MMP-1, MMP-8, MMP-9 levels was observed, with median decreases from 21% to 70%. MMP-3 and MMP-7 remained largely unchanged, and MMP-2 concentrations increased after treatment. Notably, anti-inflammatory treatment correlated with reduced post-treatment MMP levels, suggesting potential therapeutic benefit. CONCLUSIONS Distinctive inflammatory responses in COVID-19 were evident between adults and children. While certain MMPs exhibited post-treatment reduction, the persistence of elevated levels raises concerns about potential long-term consequences, including lung fibrosis. Our findings emphasize the need for personalized treatment strategies and further investigation into the dynamics of MMP regulation in COVID-19.

Diagnostic Precision in Lyme borreliosis: Assessing VlsE and C6 Antigens in a Pediatric Cohort.

(1) Background: Lyme borreliosis (LB) is a tick-borne disease known for its diagnostic challenges. Conventional two-tiered testing (CTTT) for antibodies is time-consuming, has low sensitivity in the early stages of disease, and sometimes generates false-positive IgM immunoblots. To tackle this issue, modified two-tiered testing (MTTT) was introduced, incorporating recombinant VlsE and C6 antigens to enhance diagnostic accuracy. (2) Methods: In this prospective study, we enrolled children exhibiting symptoms indicative of LB. We collected serum samples at various intervals and subjected them to analysis using standard enzyme immunoassays. We then compared these results with the outcomes from the VlsE and C6 assays. (3) Results: In our study, all 33 patients displaying erythema migrans (EM), a characteristic symptom of LB, exhibited positive responses to the C6 antigen. This finding underscores the potential utility of the C6 antigen as a reliable diagnostic tool for LB. Additionally, we observed a significant reduction in anti-VlsE antibody levels following antibiotic treatment in EM patients. (4) Conclusions: The utilization of recombinant VlsE and C6 antigens in LB diagnostics and monitoring has yielded promising results. Nonetheless, it is imperative for clinicians to exercise caution and interpret results in conjunction with clinical findings, considering the dynamic nature of medical guidelines. Even with recombinant antigen tests, some children with EM tested negative, highlighting the importance of clinical diagnosis for treatment decisions. Furthermore, clinicians should be mindful of the possibility of persistently positive VlsE/C6 test results during LB treatment monitoring.

Clinical Presentation and Co-Detection of Respiratory Pathogens in Children Under 5 Years with Non-COVID-19 Bacterial and Viral Respiratory Tract Infections: A Prospective Study in Bialystok, Poland (2021-2022).

BACKGROUND Respiratory tract infections (RTIs) in children often involve a complex interplay between viruses and bacteria. This study aimed to evaluate clinical presentation in children under 5 years old diagnosed with non-COVID-19 bacterial and viral respiratory tract co-infections between October 2021 and May 2022 in Bialystok, Poland. MATERIAL AND METHODS We recruited 100 children under 5 years with RTIs who tested negative for SARS-CoV-2. Nasopharyngeal swabs were screened for 19 viruses and 7 bacterial strains using molecular assays. RESULTS Viral pathogens were detected in 71% of patients and bacterial pathogens were detected in 59%. The most common pathogens were Haemophilus influenzae (n=48), rhinoviruses (n=32), and Streptococcus pneumoniae (n=30). Single pathogens were detected in 36%, dual in 37%, triple in 15%, and quadruple in 2%. Bacterial pathogens were co-detected with viruses in 40 cases, mostly with rhinoviruses (n=15). Two different viruses were found in 14 children and the most common co-detection was adenovirus with rhinovirus (n=5); dyspnea (63% vs 11%) and wheezing (75% vs 22%) were more common in children with human bocavirus. Fever was a common symptom in children with human adenovirus (88% vs 58%). Detection of bacteria and multiple detections were more common in day-care attendees, but were not associated with clinical picture of RTI. CONCLUSIONS Consistent with previous studies, we found a high prevalence of rhinoviruses, despite ongoing implementation of non-pharmaceutical interventions to contain the COVID-19 pandemic. Co-detection of 2 different respiratory pathogens was frequent, but we found no evidence that this was associated with the severity of infections.

The Role of Adipokines in the Pathologies of the Central Nervous System.

Adipokines are protein hormones secreted by adipose tissue in response to disruptions in physiological homeostasis within the body's systems. The regulatory functions of adipokines within the central nervous system (CNS) are multifaceted and intricate, and they have been identified in a number of pathologies. Therefore, specific adipokines have the potential to be used as biomarkers for screening purposes in neurological dysfunctions. The systematic review presented herein focuses on the analysis of the functions of various adipokines in the pathogenesis of CNS diseases. Thirteen proteins were selected for analysis through scientific databases. It was found that these proteins can be identified within the cerebrospinal fluid either by their ability to modify their molecular complex and cross the blood-brain barrier or by being endogenously produced within the CNS itself. As a result, this can correlate with their measurability during pathological processes, including Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, depression, or brain tumors.

Knowledge, Attitudes, and Behaviors Regarding Lyme Borreliosis Prevention in the Endemic Area of Northeastern Poland.

(1) Background: The incidence of Lyme borreliosis (LB) is increasing in Europe. The new LB vaccine is still in clinical development, thus the dissemination of knowledge about the disease is essential. We assessed the knowledge, attitudes and preventive practices (KAP) against tick-borne diseases (TBDs) of people living in the endemic area in northeastern Poland. (2) Methods: We surveyed 406 adults using a 37-item anonymous paper survey. The data were analyzed with regression models. (3) Results: The two most popular knowledge sources were the Internet and doctors, selected by 77.8% and 53.4%, respectively. Respondents felt moderately knowledgeable about TBDs and tick bite prophylaxis (median scores 5/10, and 6/10, respectively), considered TBDs to be a significant health threat (median 8/10), attributed high risk to tick mouthparts remaining in the skin after tick removal (median 10/10), and shared multiple misconceptions regarding LB transmission, symptoms, and management. General knowledge scores (GKS) about TBDs and tick protection practices scores (TPS) were moderate (65.0%; IQR, 55.8−71.7%, 63.6%; 54.5−72.7%, respectively). Only 48.0% had a positive attitude towards TBE vaccination. A recent tick-bite was associated with higher GKS (OR, 2.55; 95% CI, 1.27−5.10; p = 0.008), higher TPS (OR 4.76, 95% CI, 2.0−11.1; p < 0.001), and a positive attitude towards TBE vaccine (OR 2.10, 1.07−4.10, p = 0.030). A positive vaccine attitude was also associated with obtaining TBD knowledge from doctors and other verified sources (OR, 2.654, 1.66−4.23; p < 0.001). Age, place of residence, and frequent exposure to ticks in green areas were not associated with GKS, TPS, nor vaccine attitude. (4) Conclusions: Increased risk perceptions are associated with adoption of behaviors preventing TBDs. Medical professionals play an important role in communicating knowledge about TBDs. There is a need to revise current communication strategies with respect to tick bites and prevention of LB and other TBDs.

Rotavirus gastroenteritis in children hospitalized in northeastern Poland in 2006-2020: Severity, seasonal trends, and impact of immunization.

OBJECTIVES: The introduction of the rotavirus vaccine in 2006 significantly reduced childhood incidence of acute gastroenteritis (AGE) worldwide. The rotavirus vaccine was included in Poland's national immunization program in 2021. Our study aimed to summarize the epidemiology of AGE in northeastern Poland prior to 2021 and to evaluate the effectiveness of voluntary, out-of-pocket rotavirus childhood vaccination on the incidence of rotavirus AGE. METHODS: A review of patients aged 0-17 years with gastroenteritis hospitalized between 2006 and 2020 in northeastern Poland in the context of rotavirus vaccine coverage in the region. RESULTS: Rotavirus was the most common agent of gastroenteritis in hospitalized patients. The seasonality of rotavirus gastroenteritis peaked between February and May in each year of study, except for 2020, when the COVID-19 pandemic skewed any viable comparison of seasonality. Rotavirus vaccine coverage in northeastern Poland did not exceed 25% during the study period and had no impact on hospitalization numbers. CONCLUSIONS: Rotavirus was the primary causative agent of AGE in children hospitalized in northeastern Poland during the study period. Voluntary vaccinations did not affect the number of hospitalizations due to rotavirus AGE. Our data suggest that universal immunization is key to achieving a significant reduction of rotavirus-associated diarrhea.

SBA-15 Mesoporous Silica Modified with Gallic Acid and Evaluation of Its Cytotoxic Activity.

Gallic acid has been covalently conjugated to SBA-15 mesoporous silica surface through different linkers. Cytotoxic activity of the hybrid organic-inorganic systems against HeLa and KB cell lines has been analyzed. Up to 67% of HeLa or KB tumor cells growth inhibition has been achieved at low silica concentration used (10 µg mL(-1)).

Immobilization of Zidovudine Derivatives on the SBA-15 Mesoporous Silica and Evaluation of Their Cytotoxic Activity.

Novel zidovudine derivatives, able to be covalently conjugated to silica surface, have been obtained and grafted to SBA-15 mesoporous silica. Cytotoxic activity of the hybrid organic-inorganic (zidovudine derivatives-silica) systems against HeLa and KB cell lines has been analyzed. Addition of folic acid had a positive influence on the cytotoxicity. Up to 69% of HeLa and 65% of KB tumor cells growth inhibition has been achieved at low silica concentration used (10 µg/mL).

Arsenic trioxide preferentially induces nonapoptotic cell deaths as well as actin cytoskeleton rearrangement in the CHO AA8 cell line.

INTRODUCTION: The therapeutic effect of arsenic trioxide (ATO, As2O3) has been investigated for many years. However, the precise molecular mechanisms underlying the antitumor activity of ATO are still not fully understood, but seem to depend on cell types, dosage, and duration of exposure. The purpose of this study was to assess the actin cytoskeleton rearrangement during the cell death process induced by arsenic trioxide in the CHO AA8 cells. A better understanding the mechanisms of ATO-action is likely to lead to more rational use of this drug either as monotherapies or in combination with other anticancer agents. MATERIAL AND METHODS: The effect of ATO on actin cytoskeleton was studied in Chinese Hamster Ovary AA8 cell line. Actin was visualized by fluorescence microscopy and phalloidin conjugated to Alexa Fluor® 488. Morphological and ultrastructural alterations in the CHO AA8 cells were evaluated by using light and electron microscope, respectively. For quantitative measurement of cell death, Annexin V-Alexa Fluor® 488 and Propidium Iodide assay was performed. The vital staining of CHO AA8 cells with acridine orange was applied to detect the development of acidic vesicular organelles (AVOs). RESULTS: The performed experiments revealed a dose-dependent decrease in the cell survival. The morphological and ultrastructural features acquired by the cells after ATO-treatment were considered as typical for autophagy and mitotic cell death. As was shown by acridine orange staining, arsenic trioxide treatment increased red fluorescence signals in dose-dependent manner, indicating the development of AVOs, a hallmark of autophagy. Low level of apoptosis was induced in the ATO-treated CHO AA8 cells. Furthermore, the rearrangement of actin filaments associated with cell death process was also detected. CONCLUSIONS: The obtained results suggest that arsenic trioxide preferentially induces nonapoptotic cell deaths, autophagy and mitotic cell death, in p53-deficient CHO AA8 cells. Furthermore, the distinctive patterns of F-actin remodeling after As2O3 treatment were associated with different modes of cell death, confirming that cytoskeleton is a dynamic structure actively involved in the cell death process.

Double barrier as an effective method for slower delivery rate of ibuprofen.

Ibuprofen (IBU) was chosen as a model drug to investigate the drug delivery rate. Mesoporous MCM-41 has been charged with ibuprofen (MCM-41_IBU). Calcium alginate was applied to encapsulate free drug and the mesoporous material. The system with double barrier demonstrated a slower release of IBU than free ibuprofen-loaded alginate beads and MCM-41_IBU. The IBU release from alginate matrix can be controlled by adjusting the free IBU/MCM-41_IBU ratio.