Search Results (2,937)

Soil-transmitted helminths (STHs) and Herpes Simplex Virus type 2 (HSV-2) are highly prevalent infections with overlapping distribution, particularly in resource-poor regions. STH/HSV-2 co-infections may impact female reproductive health. However, many aspects of STH/HSV-2 co-infections, including the role of microRNAs (miRNAs) in regulating female genital tract (FGT) immunity and their potential contribution to pathologies such as chronic inflammation, impaired mucosal defense, and reproductive tract cancers remain unclear. In this study we investigated the miRNA expression profiles in murine FGT tissues following single or co-infection with Nippostrongylus brasiliensis (Nb) and HSV-2 and explored predicted miRNA-mRNA targets and pathways. An analysis of miRNA sequencing data was conducted to determine differentially expressed (DE) miRNAs between infected FGT tissues and uninfected controls. Ingenuity Pathway Analysis was conducted to predict the immune-related target genes of the DE miRNAs and reveal enriched canonical pathways, top diseases, and biological functions. Selected representative DE miRNAs were validated using RT-qPCR. Our results showed a total of eight DE miRNAs (mmu-miR-218-5p, mmu-miR-449a-5p, mmu-miR-497a-3p, mmu-miR-144-3p, mmu-miR-33-5p, mmu-miR-451a, mmu-miR-194-5p, and mmu-miR-192-5p) in the comparison of Nb-infected versus uninfected controls; nine DE miRNAs (mmu-miR-451a, mmu-miR-449a-5p, mmu-miR-144-3p, mmu-miR-376a-3p, mmu-miR-192-5p, mmu-miR-218-5p, mmu-miR-205-3p, mmu-miR-103-3p, and mmu-miR-200b-3p) in the comparison of HSV-2-infected versus uninfected controls; and one DE miRNA (mmu-miR-199a-5p) in the comparison of Nb/HSV-2 co-infected versus uninfected controls (p-value < 0.05, |logFC| ≥ 1). Core expression analysis showed that, among other canonical pathways, the DE miRNAs and their predicted mRNA targets were involved in neutrophil degranulation, interleukin-4 and interleukin-13 signaling, natural killer cell signaling, interferon alpha/beta signaling, and ISGylation. Additionally, cancer was predicted as one of the significantly enriched diseases, particularly in the co-infected group. This is the first study to provide insights into the FGT miRNA profiles following Nb and HSV-2 single and co-infection, as well as the predicted genes and pathways they regulate, which may influence host immunity and pathology. This study highlights the role of miRNAs in regulating FGT immunity and pathology in the context of STH/HSV-2 co-infection. Full article

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing lung disease characterized by chronic inflammation, vascular remodeling, and immune dysregulation. COVID-19, caused by SARS-CoV-2, shares several systemic immunohematologic disturbances with IPF, including cytokine storms, endothelial injury, and prothrombotic states. Unlike general comparisons of viral infections and chronic lung disease, this review offers a focused analysis of the shared hematologic and immunologic mechanisms between COVID-19 and IPF. Our aim is to better understand how SARS-CoV-2 infection may worsen disease progression in IPF and identify converging pathophysiological pathways that may inform clinical management. We conducted a narrative synthesis of the peer-reviewed literature from PubMed, Scopus, and Web of Science, focusing on clinical, experimental, and pathological studies addressing immune and coagulation abnormalities in both COVID-19 and IPF. Both diseases exhibit significant overlap in inflammatory and fibrotic signaling, particularly via the TGF-β, IL-6, and TNF-α pathways. COVID-19 amplifies coagulation disturbances and endothelial dysfunction already present in IPF, promoting microvascular thrombosis and acute exacerbations. Myeloid cell overactivation, impaired lymphocyte responses, and fibroblast proliferation are central to this shared pathophysiology. These synergistic mechanisms may accelerate fibrosis and increase mortality risk in IPF patients infected with SARS-CoV-2. This review proposes an integrative framework for understanding the hematologic and immunologic convergence of COVID-19 and IPF. Such insights are essential for refining therapeutic targets, improving prognostic stratification, and guiding early interventions in this high-risk population. Full article

Background/Objectives: Clostridioides difficile infection (CDI) is a major cause of infectious diarrhea in the inpatient and community setting. Real-world data outside the strict environment of randomized controlled trials (RCTs) are needed to improve the quality of evidence. The aim of this study was to compare different clinical outcomes of CDI patients treated with fidaxomicin with those treated with vancomycin using a representative patient population in the United States of America (USA). Methods: Comprehensive real-world data were analyzed for this retrospective observational study, provided by the TriNetX database, an international research network with electronic health records from multiple USA healthcare providers. This includes in- and outpatients treated with fidaxomicin (FDX) or vancomycin (VAN) for CDI between 01/2013 and 12/2023. The following cohorts were compared: (i) patients treated with fidaxomicin within 10 days following CDI diagnosis (FDX group) vs. (ii) patients treated with vancomycin within 10 days following CDI diagnosis (VAN group). Outcomes analysis between the two cohorts was performed after propensity score matching and included event risk and Kaplan–Meier survival analyses for the following concomitant diseases/events occurring during an observational period of 12 months following CDI diagnosis: death, sepsis, candidiasis, infections caused by vancomycin-resistant enterococci, inflammatory bowel disease, cardiovascular disease, psychological disease, central line-associated blood stream infection, surgical site infection, and ventilator-associated pneumonia. Results: Following propensity score matching, 2170 patients were included in the FDX group and VAN groups, respectively. The event risk analysis demonstrated improved outcomes of patients treated with FDX compared to VAN in 6 out of the 10 events that were analyzed. The highest risk ratio (RR) and odds ratio (OR) were found for sepsis (RR: 3.409; OR: 3.635), candidiasis (RR: 2.347; OR: 2.431), and death (RR: 1.710; OR: 1.811). The Kaplan–Meier survival analysis showed an overall survival rate until the end of the 12-month observational period of 87.06% in the FDX group and 78.49% in the VAN group (log-rank p < 0.001). Conclusions: Our comparative event risk analysis demonstrated improved outcomes for patients treated with FDX compared to VAN in most of the observed events and underlines the results of previously conducted RCTs, highlighting the beneficial role of FDX compared to VAN. Further big data analyses from other industrialized countries are needed for comparison with our observations. Full article

Non-remitting neutropenia in children and chronic idiopathic neutropenia (CIN) in adults have been described previously as peculiar subgroups of neutropenic patients carrying similar clinical and immunological features. The present collection comprising 25 subjects (16 adults and 9 children) mostly affected with mild (84%) and moderate (16%) neutropenia aimed to identify the underlying (possibly common) genetic background. The phenotype of these patients resemble the one described previously: no severe infections, presence of rheumathological signs, leukopenia in almost all patients and lymphocytopenia in one-third of the cohort. The pediatric patients did not share common genes with the adults, based on the results of the multisample test, while some singular variants in neutropenia potentially associated with immune dysregulation likely consistent with the phenotype were found. SPINK5, RELA and CARD11 were retrieved and seem to be consistent with the clinical picture characterized by neutropenia associated to immune dysregulation. The enrichment and burden tests performed in comparison with a control group underline that the products of expression by the variants involved belong to the autoimmunity and immune regulation pathways (i.e., SPINK5, PTPN22 and PSMB9). Even with the limitation of this study’s low number of patients, these results may suggest that non-remitting neutropenia and CIN in adults deserve deep genetic study and enlarged consideration in comparison with classical neutropenia. Full article

H. pylori infects over half of the global population and is associated with various gastric and extra-gastric diseases. Other species, such as zoonotic non-Helicobacter pylori Helicobacters (NHPHs), have shown similar associations with gastritis and MALT lymphoma and H. pylori-negative cases with gastric disease have been identified, including gastric MALT lymphoma, chronic gastritis, and gastroduodenal ulcers. Accurate identification of these species is of great relevance but remains challenging using conventional diagnostic methods. This cross-sectional study aimed to determine the prevalence of H. pylori and NHPH infections, comparing standard histological protocols with molecular techniques. Between December 2024 and February 2025, 54 adult patients undergoing upper gastrointestinal endoscopy (UGE) with gastric biopsy in three hospitals in Algarve, Portugal were recruited. Endoscopic assessment was performed, and gastric biopsies were collected for histological and molecular analysis. DNA was extracted from antral biopsies and analyzed by conventional PCR to detect H. pylori and NHPH. H. pylori diagnostic techniques were compared, descriptive plus statistical analysis was performed, and p-values < 0.05 were considered to be statistically significant. Fifty-four patients were included in the study, with 51.9% of them presenting symptoms. Endoscopic gastritis was observed in 66.7% of patients, while histological gastritis was present in 88.9%, with statistically significant differences between the two diagnostic techniques (p = 0.004). Helicobacter spp. were identified in 44.4% (24/54) of the patients. H. pylori was detected in 42.6% of the patients by Modified Giemsa stain and in 33.3% by PCR. H. bizzozeronii was found in 35.9% of the patients, with 22.2% showing mixed infections. This study reveals a significant prevalence of Helicobacter spp. in patients from the Algarve region, with both H. pylori and zoonotic H. bizzozeronii detected. This is the first report of H. bizzozeronii DNA detection in gastric biopsies via PCR from patients undergoing UGE in Portugal, highlighting the need to consider NHPH in clinical diagnosis. It is important to include molecular methods in routine diagnostics and the need for broader studies to assess regional and national trends in Helicobacter infections besides H. pylori. Full article

Background/Objectives:Titanium implant surface modifications enhance osseointegration and prevent microbial colonization, improving implant longevity. Antimicrobial coatings, particularly cerium- and bismuth-doped hydroxyapatite (CeHAp and BiHAp), have gained attention for reducing infection-related complications. This study evaluates the antimicrobial activity of CeHAp and BiHAp coatings on CpTi compared to untreated CpTi in artificial saliva at pH levels of 4.5, 6.5, and 8. Methods: Antibacterial efficacy against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Candida albicans (C. albicans) was assessed using the broth dilution method. Titanium rods coated with test compounds were incubated in inoculated nutrient broth, and microbial inhibition was determined via optical density at 600 nm. A statistical analysis was performed using the Kruskal–Wallis ANOVA test, the median and Interquartile Range were determined for the variables, and a Dwass–Steel–Critchlow–Fligner intergroup pairwise comparison was conducted. Results: The results showed that both the CeHAp and BiHAp coatings demonstrated significant antimicrobial activity against S. aureus (OD = 0.01) at pH 6.5, which was more pronounced than the activity observed against E. coli (OD = 0.05), with the difference being statistically significant (p = 0.001). The least antimicrobial activity was observed against C. albicans (0.21) at pH 8 (p = 0.001). Conclusion: These findings highlight the pH-dependent effectiveness of BiHAp and CeHAp coatings in inhibiting microbial growth. Their application on titanium implants may enhance antimicrobial properties, contributing to improved dental implant success and broader biomedical applications. Full article

Background: Accurate differentiation between Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM) is essential for proper diagnosis and treatment. This study compares the diagnostic performance of two commercial real-time PCR kits, AdvanSure^TM TB/NTM and Kogene PowerChek^TM MTB/NTM, for detecting MTB, NTM, and negative (no growth, NG) clinical specimens. Methods: A total of 390 clinical residual specimens were collected from patients between December 2022 and June 2023. The samples, including sputum, bronchoalveolar lavage, tracheal aspirate and body fluid, were initially tested with MGIT culture and then analyzed using both PCR kits. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were evaluated. Discrepant results between the two PCR assays were further investigated using sequencing to identify the detected mycobacterial species, and final diagnoses were verified by culture results and review of electronic medical records. Results: Of the 390 specimens, both AdvanSure^TM and PowerChek^TM real-time PCR assays demonstrated 100% sensitivity for both MTB and NTM detection. For MTB detection, AdvanSure^TM demonstrated a specificity of 100%, with a PPV, NPV, and overall accuracy all reaching 100%. In comparison, PowerChek^TM showed a specificity of 98.62%, a PPV of 96.15%, an NPV of 100%, and an overall accuracy of 98.97%. For NTM detection, both AdvanSure^TM and PowerChek^TM exhibited identical performance metrics. The specificity was 99.58% for both assays, with a PPV of 99.34%, NPV of 100%, and an overall accuracy of 99.74%. Five discrepant results were finally confirmed as four NTM detection cases and one negative case by culture and clinical diagnosis which showed four cases of PowerChek^TM MTB+NTM detection and one case of NTM detection, respectively. Conclusions: The PowerChek^TM MTB/NTM real-time PCR kit demonstrated excellent diagnostic performance for the detection of MTB and NTM, with high sensitivity, specificity, and accuracy. Minor discrepancies, particularly in detecting MTB+NTM mixed infections, highlight the importance of complementary sequencing analysis for resolving uncertain results. These findings support the clinical utility of both PCR assays as reliable tools for rapid diagnosis of mycobacterial infections. PowerChek^TM showed occasional false positives, suggesting that optimizing the assay’s cutoff threshold or amplification parameters could enhance its specificity and reduce false-positive results in clinically ambiguous cases. Full article

Background: Atypical subtrochanteric femoral fractures (ASFs), frequently linked to long-term bisphosphonate use, present significant fixation challenges due to impaired bone healing. While intramedullary (IM) nailing is the standard treatment, delayed union or nonunion remains common. This study aimed to evaluate whether supplementing IM nailing with lateral plate augmentation improves radiographic healing in patients with ASFs. Methods: This retrospective comparative study included 12 elderly female patients with ASFs treated between October 2013 and October 2023. Five patients underwent IM nailing alone (IM group), while seven received IM nailing with additional lateral plate fixation (Plate + IM group). Fracture healing was assessed using the modified Radiographic Union Score for Tibial fractures (mRUST) at 3, 6, and 12 months postoperatively. Intergroup comparisons were performed using the Mann–Whitney U test. Results: The median mRUST scores in the IM group were 4 (IQR 3.5–4), 6 (IQR 4.5–6.5), and 8 (IQR 7–9) at 3, 6, and 12 months, respectively. In the Plate + IM group, the scores were 5 (IQR 4–6), 8 (IQR 8–8), and 10 (IQR 10–11), respectively. The Plate + IM group demonstrated significantly higher mRUST scores at all assessed time points (3 months: p = 0.018; 6 months: p = 0.003; 12 months: p = 0.006). No implant failures or postoperative infections occurred in either group during the 12-month follow-up period. One patient (20%) in the IM group developed fracture nonunion, while no nonunion cases were observed in the Plate + IM group. Conclusions: Lateral plate augmentation as an adjunct to IM nailing may promote faster and more consistent radiographic healing in atypical subtrochanteric femoral fractures. This dual-fixation strategy may offer a biomechanically more robust option for patients at risk of delayed union, potentially contributing to a lower risk of nonunion, though further prospective studies are required to confirm this finding. Full article

Urinary tract infections (UTIs) are a common pathology worldwide, frequently associated with kidney stones. We aimed to determine how artificial intelligence (AI) could assist and enhance human medical activities in this field. We performed a search in PubMed using different sets of keywords. When using the keywords “AI, artificial intelligence, urinary tract infections, Escherichia coli (E. coli)”, we identified 16 papers, 12 of which fulfilled our research criteria. When using the keywords “urolithiasis, AI, artificial intelligence”, we identified 72 results, 30 of which were suitable for analysis. We identified that AI/machine learning can be used to detect Gram-negative bacilli involved in UTIs in a fast and accurate way and to detect antibiotic-resistant genes in E. coli. The most frequent AI applications for urolithiasis can be summarized into three categories: The first category relates to patient follow-up, trying to improve physical and medical conditions after specific urologic surgical procedures. The second refers to urinary stone disease (USD), focused on stone evaluation, using different AI and machine learning systems, regarding the stone’s composition in terms of uric acid, its dimensions, its volume, and its speed of detection. The third category comprises the comparison of the ChatGPT-4, Bing AI, Grok, Claude, and Perplexity chatbots in different applications for urolithiasis. ChatGPT-4 has received the most positive evaluations. In conclusion, the impressive number of papers published on different applications of AI in UTIs and urology suggest that machine learning will be exploited effectively in the near future to optimize patient follow-up, diagnosis, and treatment. Full article

Background: Solid Organ Transplant Recipients (SOTRs) face an elevated risk of Sars-CoV-2 infection and poor outcomes if they contract the infection. This can induce or exacerbate anxiety and depressive symptoms. We used the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety (A) and Depression (D) scores to conduct a repeated cross-sectional (“pseudo-longitudinal”) comparison of SOTRs’ anxiety and depressive symptoms before and after the COVID-19 pandemic onset. Methods: This secondary analysis used cross-sectional data from a convenience sample of adult SOTRs (kidney, kidney–pancreas, and liver) recruited between 2016 and 2024. The exposure was categorized as follows: “Pandemic Experience” was categorized as PRE (pre-pandemic reference; transplanted and anxiety and depressive symptoms assessed pre-pandemic onset), POST-1 (transplanted before and assessed after onset), and POST-2 (transplanted and assessed after onset). The outcomes were PROMIS-A and PROMIS-D scores. The differences were assessed using multivariable linear regression-estimated means. Results: Of the 816 participants, 588 (72%) were PRE, 135 (17%) were POST-1, and 93 (11%) were POST-2. In the fully adjusted model, the POST-2 group had significantly higher PROMIS-A scores (more severe symptoms) compared with PRE (adjusted mean [95% CI]: 54.2 [52.3; 56.1] vs. 51.7 [50.9; 52.4], p = 0.02). The proportion of patients with potentially clinically significant anxiety was also higher in the POST-2 group, compared with PRE (OR [95%CI] 1.59 [1.0; 2.5]). The PROMIS-A scores were similar between PRE and POST-1, and between POST-1 and POST-2. The PROMIS-D scores were not different across the exposure groups. Conclusions: SOTRs transplanted after the pandemic onset experienced more anxiety but similar depression symptoms compared with pre-pandemic levels. Future research should explore mental health support for SOTRs during crisis situations involving infectious risk. Full article

Background: COVID-19 has been linked to prolonged immune dysfunction and long-term health complications. Herpes zoster (HZ), a marker of impaired cell-mediated immunity, may signal increased vulnerability to infections, cardiovascular disease, and potentially cancer. However, its association with colorectal cancer (CRC) after COVID-19 has not been fully explored. Objective: To investigate the long-term risks of cardiovascular events, acute respiratory failure, sepsis, and CRC in COVID-19 survivors who developed HZ compared to those who did not. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adults diagnosed with COVID-19 between January 2020 and January 2022 were included. Among the full cohort (aged ≥18 years), 27,664 patients with post-COVID HZ were identified. Due to platform limitations, propensity score matching (PSM) was applied to a restricted subgroup of patients aged 55–60 years, yielding a 1:1 matched cohort for controlled comparisons. Outcomes were assessed over a three-year follow-up. Results: In the matched age-restricted cohort, patients with post-COVID HZ had significantly higher risks of cardiovascular events, acute respiratory failure, sepsis, and CRC compared to matched controls. Subgroup analyses identified age ≥ 50, chronic kidney disease, diabetes, and hypertension as strong independent risk factors across outcomes. Despite the low absolute CRC incidence, cancer-free survival significantly favored the non-HZ group. Conclusion: Herpes zoster reactivation after COVID-19 is associated with increased risk of colorectal cancer. Enhanced surveillance and early CRC screening may benefit this high-risk population. Full article

The Steinernema carpocapsae nematode is known to release several excretory/secretory products (ESPs) in its venom upon contact and during the parasitic infection process of insect hosts. A recurrent family of proteins found in this nematode’s venom is the CAP (cysteine-rich secretory protein/antigen 5/pathogenesis-related 1) protein, but the functional role of these proteins remains unknown. To elucidate the biological function, this study focused on characterising the secreted protein, first identified in the venom of the nematode’s parasitic stage, and the sequence retrieved from transcriptomic analysis. The structural comparisons of the Sc-CAP protein model, as determined by AlphaFold2, revealed related structures from other parasitic nematodes of vertebrates. Some of these closely related proteins are reported to have sterol-binding ability. The Sc-CAP recombinant protein was successfully produced in Escherichia coli in conjunction with a chaperone protein. The results showed that the Sc-CAP protein binds to cholesterol, and docking analyses of sterols on the protein revealed potential molecular interactions. Immunoassays performed in Galleria mellonella larvae revealed that this venom protein has an inhibitory effect against phenoloxidase and the antimicrobial response of insects. This suggests that the venom protein has an immunomodulatory function against insects, emphasising its importance during the parasite–host interaction. Full article

This study investigates the capability of Sentinel-1 (S1) SAR time series to identify vegetation sites affected by pest infestations. For this purpose, the statistical method of the Fisher–Shannon analysis was employed to discern infected from unifected forest trees. The analysis was performed on a case study (Castel Porziano) located in the urban and peri-urban areas of Rome (Italy), which have been significantly impacted by Toumeyella parvicornis (TP) in recent years. For comparison, the area of Follonica (Italy), which has not yet been affected by this insect, was also analyzed. Two polarizations (VV and VH) and two orbit types (Ascending and Descending) were analyzed. The results, supported by Receiver Operating Characteristic (ROC) analysis, demonstrated that VH polarization in the Descending orbit provided the best performance in identifying TP-infected sites. Full article

Background: Iminosugars are natural or synthetic sugar analogues with a very broad spectrum of activities, including those against the most prominent bacterial pathogens, like P. aeruginosa or S. aureus. In a series of studies, we have demonstrated that one of the synthetic iminosugars, PDIA (beta-1-C-propyl-1,4-dideoxy-1,4-imino-L-arabinitol), possesses the ability to suppress biofilm production by different pathogenic bacteria without inhibiting their growth. Thereby, PDIA is able to influence experimental skin infection caused by S. aureus. Methods: To elucidate molecular mechanisms by which PDIA impedes biofilm formation by S. aureus, a transcriptomic study was performed in which a biofilm-producing S. aureus strain was grown in the presence of PDIA for 24 and 48 h in comparison to a control without the iminosugar. The RNA was then isolated, converted into cDNA, sequenced, and data analysis was performed. Results: It appeared that PDIA caused the down-regulation of many bacteriophage genes responsible for the processes of bacterial cell lysis, and some genes responsible for cell wall degradation were also down-regulated. Among the 25 most upregulated genes were those representing the phosphotransferase system (PTS), which is required for carbohydrate uptake and control of carbon metabolism. The ranking of the most significant down-regulated genes after 24 h exposure to PDIA shows that they predominantly coded for both the synthesis and lysis of the peptidoglycan. Conclusions: We have shown here that the influence of PDIA on the expression of S. aureus genes is broad and affects many genes encoding metabolism and ribosomes. Full article

Immunosuppressants are essential for preventing allograft rejection; however, they require therapeutic drug monitoring to maintain efficacy and to prevent severe complications such as opportunistic infections. Calcineurin inhibitors (CIs) are primarily distributed in red blood cells, whereas mycophenolic acid (MPA) and its metabolites are found in plasma. These differences necessitate separate analyses for each drug, increasing laboratory workload, analytical complexity, and patient burden. We developed a liquid chromatography–tandem mass spectrometry method for simultaneous quantification of CIs such as tacrolimus (Tac), everolimus (Eve), sirolimus (Sir), cyclosporine A (CycA) and MPA in 2.8-µL whole-blood samples, with a hematocrit-based correction to estimate plasma-equivalent MPA concentrations. Performance of this method was assessed by comparison with conventional immunoassay results using linear regression and Bland–Altman analyses, demonstrating excellent agreement, with strong linearity (R² > 0.995) at <2 to 35 ng/mL for three CIs, 26.0 to 1866 ng/mL for CycA, and 0.1 to 50 μg/mL for MPA. Furthermore, MPA and tacrolimus concentrations closely aligned with routine clinical results (R² > 0.900), indicating high accuracy and reproducibility. This new approach may be particularly beneficial for hospitalized patients with limited venous access, pediatric populations, and in remote care settings where frequent blood sampling is challenging because of simultaneous quantification and fewer sample volume requirements. Full article