Search Results (5,779)

Background and Objectives: Accurately diagnosing acute appendicitis (AA) in children remains clinically challenging due to overlapping symptoms with other pediatric conditions and limitations in conventional diagnostic tools. The systemic immune-inflammation index (SII) has emerged as a promising biomarker in adult populations; however, its utility in pediatrics is still unclear. This study aimed to evaluate the diagnostic accuracy of SII in distinguishing pediatric acute appendicitis from elective non-inflammatory surgical procedures and to assess its predictive value in identifying complicated cases. Materials and Methods: This retrospective, single-center study included 397 pediatric patients (5–15 years), comprising 297 histopathologically confirmed appendicitis cases and 100 controls. Demographic and laboratory data were recorded at admission. Inflammatory indices including SII, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were calculated. ROC curve analysis was performed to evaluate diagnostic performance. Results: SII values were significantly higher in the appendicitis group (median: 2218.4 vs. 356.3; p < 0.001). SII demonstrated excellent diagnostic accuracy for AA (AUROC = 0.95, 95% CI: 0.92–0.97), with 91% sensitivity and 88% specificity at a cut-off > 624. In predicting complicated appendicitis, SII showed moderate discriminative ability (AUROC = 0.66, 95% CI: 0.60–0.73), with 83% sensitivity but limited specificity (43%). Conclusions: SII is a reliable and easily obtainable biomarker for diagnosing pediatric acute appendicitis and may aid in early detection of complicated cases. Its integration into clinical workflows may enhance diagnostic precision, particularly in resource-limited settings. Age-specific validation studies are warranted to confirm its broader applicability. Full article

The gut microbiota of macaques, highly homologous to humans in biological characteristics and metabolic functions, serves as an ideal model for studying the mechanisms of human intestinal diseases and therapeutic approaches. A comprehensive characterization of the macaque gut microbiota provides unique insights into human health and disease. This study employs metagenomic sequencing to assess the gut microbiota of wild M. mulatta brevicaudus across various ages, sexes, and physiological states. The results revealed that the dominant bacterial species in various age groups included Segatella copri and Bifidobacterium adolescentis. The predominant bacterial species in various sexes included Alistipes senegalensis and Parabacteroides (specifically Parabacteroides merdae, Parabacteroides johnsonii, and Parabacteroides sp. CT06). The dominant species during lactation and non-lactation periods were identified as Alistipes indistinctus and Capnocytophaga haemolytica. Functional analysis revealed significant enrichment in pathways such as global and overview maps, carbohydrate metabolism and amino acid metabolism. This study enhances our understanding of how age, sex, and physiological states shape the gut microbiota in M. mulatta brevicaudus, offering a foundation for future research on (1) host–microbiome interactions in primate evolution, and (2) translational applications in human health, such as microbiome-based therapies for metabolic or immune-related disorders. Full article

Platelet-rich plasma (PRP) is widely applied in veterinary regenerative medicine due to its rich composition of growth factors that promote tissue repair. However, the direct pro-angiogenic function of canine PRP (cPRP) has not been thoroughly validated through controlled in vitro and in vivo experimentation. Human umbilical vein endothelial cells (HUVECs) were used to assess cell proliferation, migration, and tube formation after exposure to cPRP. In addition, a rabbit corneal micropocket assay was employed to evaluate in vivo angiogenic responses. Treatment with 20% cPRP significantly enhanced HUVEC proliferation and migration and induced robust tube formation. In the in vivo model, we observed dose-dependent neovascularization, with the earliest vascular sprouting seen on day 1 in the 40% group. Both models consistently demonstrated that cPRP stimulates vascular development in a concentration-dependent manner. This study provides novel evidence of cPRP’s capacity to induce neovascularization, supporting its therapeutic value for treating nonhealing wounds in dogs, especially in cases involving chronic inflammation, aging, or immune dysregulation. These findings offer a scientific foundation for the broader clinical application of cPRP in veterinary regenerative practice. Full article

Endometriosis is a chronic inflammatory condition affecting approximately 10% of women of reproductive age, characterized by pelvic pain, dysmenorrhea, and infertility. Emerging evidence suggests a potential link between gut microbiota dysbiosis and endometriosis pathogenesis, mediated through hormonal regulation, immune modulation, and systemic inflammation. Dienogest (DNG) is widely used for endometriosis management, but its effects on gut microbiota remain underexplored. This study investigates the impact of DNG on gut microbial composition in endometriosis patients, aiming to elucidate its therapeutic mechanisms beyond hormonal modulation. DNG therapy led to a significant reduction in the Bacillota/Bacteroidota ratio (p = 0.0421), driven by decreased Staphylococcus spp. (p = 0.0244) and increased commensal bacteria such as Lactobacillus spp. and Collinsella aerofaciens (p = 0.049). Species richness and alpha diversity indices showed a non-significant upward trend. Notably, C. aerofaciens, a butyrate producer linked to gut barrier integrity, was detected twice as frequently during therapy. The study also observed reductions in facultative anaerobes like Enterococcus spp. and a trend toward higher titers of beneficial Bacteroidota. This study provides the first evidence that DNG therapy modulates gut microbiota in endometriosis patients, favoring a composition associated with anti-inflammatory and barrier-protective effects. The observed shifts—reduced opportunistic pathogens and increased symbionts—suggest a novel mechanism for DNG’s efficacy, potentially involving the microbial regulation of estrogen metabolism and immune responses. Full article

Background: Colorectal cancer (CRC) is strongly influenced by miRNAs as well as the circadian system. Methods: High-throughput sequencing of miRNAs expressed in the rat colon during 24 h light (L)/dark (D) cycle was performed to identify rhythmically expressed miRNAs. The role of miR-150-5p in CRC progression was analyzed in DLD1 cell line and human CRC tissues. Results: Nearly 10% of mature miRNAs showed a daily rhythm in expression. A peak of miRNAs’ levels was in most cases observed during the first half of the D phase of the LD cycle. The highest amplitude was detected in expression of miR-150-5p and miR-142-3p. In the L phase of the LD cycle, the maximum in miR-30d-5p expression was detected. Gene ontology enrichment analysis revealed that genes interfering with miRNAs with peak expression during the D phase influence apoptosis, angiogenesis, the immune system, and EGF and TGF-beta signaling. Rhythm in miR-150-5p, miR-142-3p, and miR-30d-5p expression was confirmed by real-time PCR. Oncogenes bcl2 and myb and clock gene cry1 were identified as miR-150-5p targets. miR-150-5p administration promoted camptothecin-induced apoptosis. Expression of myb showed a rhythmic profile in DLD1 cells with inverted acrophase with respect to miR-150-5p. miR-150-5p was decreased in cancer compared to adjacent tissue in CRC patients. Decrease in miR-150-5p was age dependent. Older patients with lower expression of miR-150-5p and higher expression of cry1 showed worse survival in comparison with younger patients. Conclusions: miRNA signaling differs between the L and D phases of the LD cycle. miR-150-5p, targeting myb, bcl2, and cry1, can influence CRC progression in a phase-dependent manner. Full article

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infections (ALRIs) in young children, especially bronchiolitis, with significant global health and economic impact. Increasing evidence links early-life RSV infection to long-term respiratory complications, notably recurrent wheezing and asthma. This narrative review examines these associations, emphasizing predictive factors and emerging biomarkers for risk stratification. Early RSV infection can trigger persistent airway inflammation and immune dysregulation, increasing the likelihood of chronic respiratory outcomes. Risk factors include severity of the initial infection, age at exposure, genetic susceptibility, prematurity, air pollution, and tobacco smoke. Biomarkers such as cytokines and chemokines are showing promise in identifying children at higher risk, potentially guiding early interventions. RSV-related bronchiolitis may also induce airway remodeling and promote Th2/Th17-skewed immune responses, mechanisms closely linked to asthma development. Advances in molecular profiling are shedding light on these pathways, suggesting novel targets for early therapeutic strategies. Furthermore, passive immunization and maternal vaccination offer promising approaches to reducing both acute and long-term RSV-related morbidity. A deeper understanding of RSV’s prolonged impact is essential to develop targeted prevention, enhance risk prediction, and improve long-term respiratory health in children. Future studies should aim to validate biomarkers and refine immunoprophylactic strategies. Full article

Mycosis is caused by, among other factors, filamentous fungi, ubiquitous molds belonging to Aspergillus spp. which are often opportunistic pathogens. Over 100 species of Aspergillus have been described. The most common species responsible for diseases in humans and animals are Aspergillus fumigatus and Aspergillus niger, with Aspergillus flavus and Aspergillus clavatus being somewhat rarer. Aspergillus causes a range of diseases, from localized colonization and hypersensitivity reactions, through chronic necrotizing infections, to rapidly progressing angioinvasion and dissemination, leading to death. Testicular mycosis is extremely rarely described in both humans and animals. No studies in the literature report a simultaneous occurrence of testicular tumors and fungal infection of the organ, so the aim of this paper was to describe, for the first time, a case of two independent testicular tumors coexisting with testicular mycosis. A histopathological examination was performed on the left testicle of a male dog, specifically a mixed-breed dog resembling a husky weighing 22 kg and with an age of 8 years. Bilateral orchidectomy was performed for medical reasons due to the altered outline of the left testicle, leading to scrotal deformation. The dog did not show any clinical signs of illness, and the testicles were not painful. The right testicle, according to the operating veterinarian, showed no macroscopic changes, so histopathological verification was not performed. Microscopic imaging of the changes clearly indicated the coexistence of a tumor process involving Leydig cells (Leydigoma, interstitial cell tumor, ICT), Sertoli cells (Sertolioma), and fungal infection of the testis. The case suggests the possibility of the coexistence of tumor processes, which may have impaired local immune response of the tissue, with an infectious, in this case fungal, inflammatory process. Based on the literature, this paper is the first report on the occurrence of two independent histotype testicular tumors and their associated mycosis. Full article

Background: The 2022 conflict in Ukraine triggered mass migration, leading to a significant influx of Ukrainian refugee children into Poland. This situation raises concerns about hepatitis B virus immunity, as Ukraine’s hepatitis B vaccination coverage has been inconsistent compared to Poland’s high vaccination rates. Objective: To evaluate hepatitis B immunity and infection prevalence among Ukrainian refugee children residing in Southern Poland and to assess implications for vaccination strategies in the host country. Methods: A prospective cross-sectional study was conducted on 1322 Ukrainian refugee children (0–18 years) presenting to a pediatric infectious diseases department in Southern Poland between February 2022 and March 2024. Data on vaccination history, demographic characteristics, and selected laboratory parameters, including hepatitis B surface antigen and anti-HBs antibody levels, were collected. Protective immunity was defined as anti-HBs antibody levels ≥10 IU/L. Results: Among the participants (mean age 9.9 years; 50.2% female), 83.2% were reported as vaccinated according to national immunization programs, but only 64.9% demonstrated protective anti-HBs antibody levels. Protective antibody prevalence declined significantly with age, with less than half of adolescents aged 15–18 years showing immunity. Five children (0.4%) were diagnosed with chronic hepatitis B, four of whom were unvaccinated. Conclusions: This study identifies a significant gap in hepatitis B immunity among Ukrainian adolescent refugees residing in Southern Poland, with less than half possessing protective anti-HBs antibody levels. This immunity gap and the high risk of sexual transmission of the hepatitis B virus in adolescents highlight the urgent need for comprehensive surveillance, screening, and catch-up vaccination programs. Full article

Background: Despite decades of high childhood vaccination coverage, pertussis has re-emerged in the Autonomous Province of Vojvodina (AP Vojvodina), Serbia. We aimed to describe the temporal, seasonal, and age-specific patterns of pertussis in AP Vojvodina and to analyze trends by vaccination status in order to highlight changes in epidemiology and potential gaps in vaccine-induced protection. Methods: We retrospectively analyzed 2796 pertussis cases reported between January 1997 and December 2024, examining temporal, seasonal, and age-specific trends, stratifying by vaccination status across four consecutive periods (1997–2003, 2004–2010, 2011–2017, and 2018–2024). Results: Throughout the 28-year period, after low and sporadic cases in the pre-2012 period, a dramatic rise was observed in 2014, 2017, and 2018, culminating in the highest annual number of reported cases in 2024 (1011 cases). Throughout this period, primary vaccination coverage with the DTwP/DTaP three-dose series ranged between 91% and 98%, while first booster coverage gradually declined from 98% in the early 2000s to 83% in 2024. Regarding seasonality, a sharp increase in cases began in 2012, peaking in November 2023 (>350 cases) and early 2024 (312 in January, 268 in February), with a seasonal shift from summer peaks in the 2011–2017 period to higher incidence rates during colder months more recently. Adolescents aged 10–14 years had the highest cumulative incidence (1149.4/100,000), followed by infants under 12 months (978.5/100,000), despite the latter representing fewer absolute cases. The proportion of pertussis in fully vaccinated individuals rose from 6.3% (1997–2003) to 49.7% (2018–2024). Conclusions: These findings suggest that booster immunization in adolescence and routine maternal vaccination during pregnancy could reduce transmission, particularly to infants. Enhanced surveillance and updated immunization policies are critical to mitigating future pertussis outbreaks. Full article

This story began half a century ago with the discovery of an unusually high presence of tryptophan (Trp, W) in transthyretin (TTR), one of the three carrier proteins of thyroid hormones. With the Trp-rich retinol-binding protein (RBP), TTR forms a plasma complex implicated in the delivery of retinoid compounds to body tissues. W has the lowest concentration among all AAs involved in the sequencing of human body proteins. The present review proposes molecular maps focusing on the ratio of W/AA residues found in the sequence of proteins involved in immune events, allowing us to ascribe the guidance of inflammatory processes as fully under the influence of W. Under the control of cytokine stimulation, plasma biomarkers of protein nutritional status work in concert with major acute-phase reactants (APRs) and with carrier proteins to release, in a free and active form, their W and hormonal ligands, interacting to generate hot spots affecting the course of acute stress disorders. The prognostic inflammatory and nutritional index (PINI) scoring formula contributes to identifying the respective roles played by each of the components prevailing during the progression of the disease. Glucagon demonstrates ambivalent properties, remaining passive under steady-state conditions while displaying stronger effects after cytokine activation. In developing countries, inappropriate weaning periods lead to toddlers eating W-deficient cereals as a staple, causing a dramatic reduction in the levels of W-rich biomarkers in plasma, constituting a novel nutritional deficiency at the global scale. Appropriate counseling should be set up using W implementations to cover the weaning period and extended until school age. In adult and elderly subjects, the helpful immune protections provided by W may be hindered by the surge in harmful catabolites with the occurrence of chronic complications, which can have a significant public health impact but lack the uncontrolled surges in PINI observed in young infants and teenagers. Biomarkers of neurodegenerative and neoplastic disorders measured in elderly patients indicate the slow-moving elevation of APRs due to rampant degradation processes. Full article

Background/Objectives: The aim of this study was to systematically assess Adverse Events Following Immunization (AEFI) among children following administration of the human papillomavirus (HPV) vaccine (Cervarix^®) included in the Dutch National Immunization Program (NIP) and to characterize the pattern and recurrence risk of AEFI after HPV revaccination. Methods: A longitudinal cohort event monitoring study, using patient-reported outcomes was used among recipients of the HPV vaccine at 10 years of age. Data were available for 3063 children following the first HPV vaccination and for 2209 children following the second HPV vaccination. Results: The most commonly reported AEFI following HPV vaccination were injection site reactions—reported by 46.5% of participants after the first dose and 31.9% after the second dose—followed by headache (8.2% and 3.9%, respectively) and joint pain (4.5% and 3.7%, respectively). Participants who received both HPV vaccine doses reported more AEFI after the first dose than after the second. Among girls, 61.2% reported at least one AEFI following the first dose, compared to 44.2% after the second dose. For boys, these percentages were 55.3% and 38.5%, respectively. This difference was statistically significant (p = 0.002). For some AEFI, such as injection site reactions, there appears to be a potential increased risk of recurrence following the second dose. Conclusions: This prospective longitudinal cohort event monitoring study showed that AEFI were more frequent after the first HPV dose and more frequent for girls compared to boys. An increased risk of recurrence was seen for AEFI, such as injection site reactions and headache. Furthermore, this study provides insight into the course of AEFI and the extent to which children were affected by these symptoms based on real-world data. Full article

Background/Objectives: Endometriosis is a chronic, estrogen-driven gynecological disorder affecting approximately 10% of reproductive-aged women worldwide, with significant physical, psychosocial, and socioeconomic impacts. Recent research suggests a possible involvement of the gut microbiome in endometriosis disease mechanisms through immune manipulation, estrogen metabolism, and inflammatory networks. This narrative review aims to summarize current evidence on gut microbiota changes in endometriosis patients, explore the mechanisms by which gut dysbiosis contributes to disease progression, and examine epidemiological links between gastrointestinal health and endometriosis risk. Methods: A narrative review was conducted to synthesize available literature on the compositional changes in gut microbiota associated with endometriosis. The review also evaluated studies investigating potential mechanisms and epidemiological patterns connecting gut health with endometriosis development and severity. Results: Alterations in gut microbiota composition were observed in endometriosis patients, suggesting roles in immune dysregulation, estrogen metabolism, and inflammation. Potential gut-oriented interventions, including dietary changes, probiotics, and lifestyle modifications, emerged as promising management options. However, methodological variability and research gaps remain barriers to clinical translation. Conclusions: Integrating gut microbiome research into endometriosis management holds potential for improving early diagnosis, patient outcomes, and healthcare system sustainability. The study emphasizes the need for further research to address existing challenges and to develop public health strategies that incorporate microbiome-based interventions in population-level endometriosis care. Full article

Background: Immunization is a highly effective intervention for controlling over 20 life-threatening infectious diseases, significantly reducing both morbidity and mortality rates. One notable achievement in vaccination efforts was the global eradication of smallpox, which the World Health Assembly declared on 8 May 1980. Additionally, there has been a remarkable 99.9% reduction in wild poliovirus cases since 1988, decreasing from more than 350,000 cases that year to just 30 cases in 2022. Objectives: The objective of this review was to assess the effects of various interventions designed to increase vaccination uptake among adults. Search Methods: A thorough search was conducted in the CENTRAL, Embase Ovid, Medline Ovid, PubMed, Web of Science, and Global Index Medicus databases for primary studies. This search was conducted in August 2021 and updated in November 2024. Selection Criteria: Randomized trials were eligible for inclusion in this review, regardless of publication status or language. Data Analysis: Two authors independently screened the search outputs to select potentially eligible studies. Risk ratios (RR) with 95% confidence intervals (CI) were calculated for each randomized controlled trial (RCT). A meta-analysis was conducted using a random-effects model, and the quality of the evidence was assessed using the GRADE approach. Main Results: A total of 35 randomized controlled trials met the inclusion criteria and were included in this review, with the majority conducted in the United States. The interventions targeted adults aged 18 and older who were eligible for vaccination, involving a total of 403,709 participants. The overall pooled results for interventions aimed at increasing influenza vaccination showed a risk ratio of 1.41 (95% CI: 1.15, 1.73). Most studies focused on influenza vaccination (18 studies), while the remaining studies examined various other vaccines, including those for hepatitis A, COVID-19, hepatitis B, pneumococcal disease, tetanus, diphtheria, pertussis (Tdap), herpes zoster, and human papillomavirus (HPV). The results indicate that letter reminders were slightly effective in increasing influenza vaccination uptake compared to the control group (RR: 1.75, 95% CI: 0.97, 1.16; 6 studies; 161,495 participants; low-certainty evidence). Additionally, participants who received education interventions showed increased levels of influenza vaccination uptake compared to those in the control group (RR: 1.88, 95% CI: 0.61, 5.76; 3 studies; 1318 participants; low-certainty evidence). Furthermore, tracking and outreach interventions also led to an increase in influenza vaccination uptake (RR: 1.87, 95% CI: 0.78, 4.46; 2 studies; 33,752 participants; low-certainty evidence). Conclusions: Letter reminders and educational interventions targeted at recipients are effective in increasing vaccination uptake compared to control groups. Full article

β-hydroxybutyrate (BHB) is the most abundant ketone body produced during ketosis, a process initiated by glucose depletion and the β-oxidation of fatty acids in hepatocytes. Traditionally recognized as an alternative energy substrate during fasting, caloric restriction, and starvation, BHB has gained attention for its diverse signaling roles in various physiological processes. This review explores the emerging therapeutic potential of BHB in the context of sarcopenia, metabolic disorders, and neurodegenerative diseases. BHB influences gene expression, lipid metabolism, and inflammation through its inhibition of Class I Histone deacetylases (HDACs) and activation of G-protein-coupled receptors (GPCRs), specifically HCAR2 and FFAR3. These actions lead to enhanced mitochondrial function, reduced oxidative stress, and regulation of inflammatory pathways, with implication for muscle maintenance, neuroprotection, and metabolic regulation. Moreover, BHB’s ability to modulate adipose tissue lipolysis and immune responses highlight its broader potential in managing chronic metabolic conditions and aging. While these findings show BHB as a promising therapeutic agent, further research is required to determine optimal dosing strategies, long-term effects, and its translational potential in clinical settings. Understanding BHB’s mechanisms will facilitate its development as a novel therapeutic strategy for multiple organ systems affected by aging and disease. Full article

This study aimed to estimate the end-of-season influenza vaccine effectiveness (VE) for the 2024/25 season in Beijing, China. Methods: We used a test-negative design (TND) to assess influenza VE among outpatients with influenza-like illness (ILI) enrolled through the influenza virological surveillance in sentinel hospitals in Beijing from week 44, 2024 to week 14, 2025. Cases were ILI patients who tested positive for influenza; controls were those who tested negative. Results: Among 18,405 ILI patients tested, 3690 (20.0%) were positive for influenza, with A(H1N1)pdm09 as the predominant strain (98.9%). The overall influenza vaccination coverage was 12.4%. Adjusted VE was 48.3% (95%CI: 40.4%–55.3%) against any influenza and 48.2% (95%CI: 40.3%–55.1%) against A(H1N1)pdm09, with the highest VE observed in adults aged 18–59 years (79.0%). The adjusted VE was similar for those vaccinated in 2023/24 only (53.1%) or both 2023/24 and 2024/25 seasons (50.8%), but lower for those vaccinated only in the 2024/25 season (48.5%). The adjusted VE was higher during the epidemic period (52.5%) than in the pre-epidemic (48.1%) and post-epidemic (35.3%) periods. Conclusions: Our findings indicate moderate VE against laboratory-confirmed influenza, especially A(H1N1)pdm09, during the end of the 2024/25 season in Beijing, China. Influenza vaccination provided protective effects across different epidemic periods. These timely estimates support ongoing public health communication and immunization strategies. Full article