Search Results (120)

Background: Peyronie’s disease (PD) is a chronic inflammatory condition that affects the penile albuginea. Oxidative stress (OS) plays a crucial role in the development of the disease, prompting us to investigate OS levels at the site of the disease and in peripheral blood. This article presents our second study in which the OS was evaluated by calculating the OS index (OSI) in blood samples taken directly from the penile corpora cavernosa of patients with PD. Our innovative diagnostic method, which focuses on the analysis of oxidative stress (OS) in the corpora cavernosa of the penis, allows us to accurately identify the “chemical” signals (OS levels) of the pathology in the area where it is present. Methods: Our study included 102 PD patients from our Peyronie’s care center and 100 control cases. To conduct a comprehensive OS analysis, we measured both the total oxidant status (TOS) and total antioxidant status (TAS) and calculated the oxidative stress index (OSI) as OSI = TOS/TAS × 100. Blood samples were collected from the penis and a vein in the upper extremity, and OS was measured using d-ROMs and PATs (FRAS kit). Results: Pearson’s analyses revealed a significant statistical correlation between penile OSI values and PD plaque volumes (p = 0.003), while no correlation was found between systemic OSI values and plaque volumes (p = 0.356). Penile OSI values decreased significantly after PD plaque removal (p < 0.0001). A comparison of penile OSI values in PD patients (post plaque removal) and the control group showed no significant differences (p = 0.418). Conclusions: The lack of correlation between systemic OSI values and Peyronie’s plaque volume suggests that direct sampling from the site of the disease is preferable for OS studies. Conducting a penile OSI study could provide a precise oxidative marker dependent on plaque volume. In addition, the penile OSI study can biochemically monitor the therapeutic result, alongside penile ultrasound imaging. Full article

Background: SERPINE1, also known as plasminogen activator inhibitor (PAI), has been proposed as a potential blood biomarker for the early detection and diagnosis of Alzheimer’s disease (AD). Expanding on previous studies, this research contrasted SERPINE1 levels in CSF and brain tissue of AD patients and those at risk for AD with established AD biomarkers. Methods: Utilizing OLINK and immunoassay methods, CSF SERPINE1 protein levels were quantified across two separate cohorts: PREVENT-AD and ADNI. Microarray and RNAseq were used to measure tissue SERPINE1 mRNA levels in two separate cohorts: the Douglas-Bell Canada Brain Bank and the Mayo Clinic Brain Bank. Results: At the pre-clinical stage, elevated CSF levels of pTau, tTau and synaptic markers, alongside reduced hippocampal volume, correlate with CSF SERPINE1 levels. Elevated cortical SERPINE1 mRNA levels in autopsy-confirmed AD show weak correlation with regional plaques and tangles densities, but strong correlation with Braak staging. Conclusions: CSF SERPINE1 levels can be used as an early biomarker for the detection of pathological changes associated with AD. Higher SERPINE1 levels correlate more strongly with tau pathology than with amyloid formation or deposition. Full article

This review highlights recent insights into the pathophysiology and therapeutic strategies for improving biocompatibility in hemodialysis. Hemodialysis activates the innate immune system, particularly the complement cascade and neutrophils, leading to acute microinflammation. Interleukin-8 (IL-8), which increases during dialysis, promotes neutrophil chemotaxis and neutrophil extracellular trap (NET) formation, triggering myeloperoxidase (MPO) release and oxidative stress. Neutrophil accumulation in atherosclerotic plaques exacerbates vascular inflammation through IL-6 upregulation. Elevated levels of IL-8, MPO, and NET-related biomarkers are associated with increased all-cause and cardiovascular mortality in dialysis patients. Strategies to mitigate these effects include the use of advanced membrane materials (e.g., AN69, vitamin E-coated, polymethyl methacrylate), novel dialysis modalities (e.g., high-volume online hemodiafiltration, cool dialysate, hydrogen-enriched dialysate), and citrate-based anticoagulation. These approaches aim to suppress complement activation, reduce oxidative stress, and limit neutrophil-induced damage. Enhancing biocompatibility is crucial for reducing cardiovascular complications and improving outcomes in dialysis patients. Suppressing the innate immune response during dialysis may become a future cornerstone in extracorporeal blood purification therapy. Full article

Background: The behavior of soft tissues following recession type 1 (RT1) and/or non-carious cervical lesions (NCCLs) treated with class V restorations is not well understood. These conditions cause both functional and esthetic issues. Recent studies show that increased cervical thickness can influence gingival tissue response. This suggests that restoration design has a key impact. This study aims to evaluate the effect of tooth shape modification on gingival tissue response and periodontal health with 3D analysis. Methods: Seven patients with buccal gingival recession and NCCL were selected, resulting in 50 treated teeth. Patients underwent class V buccal restorations using the BOVR technique. Three-dimensional evaluation through scanned dental impressions was performed at baseline and at T1 to monitor tissue profile changes in the buccal zenith sagittal plane. The average observation period was 4 months. Following the assessment, linear measurements were calculated according to standard planes. These measurements aimed to monitor transverse and axial tissue modifications. Probing depth, plaque index, and bleeding index were also recorded. Results: Increased tooth thickness led to tissue alteration. Greater composite thickness was significantly associated with an increase in tissue thickness (p ≤ 0.001) and gingival creeping (p ≤ 0.001) at the free gingival margin. Periodontal health remained unaffected, and 50% of the teeth required no additional surgical treatment due to satisfactory outcomes. Conclusions: Class V restorations that increase cervical thickness may promote soft tissue volume gain over a 4-month period without compromising periodontal health. A 4-month observation period is recommended before considering the surgical correction. Full article

The onset of Alzheimer’s disease (AD) is attributed to widespread amyloid beta (Aβ) plaque accumulation, tau hyperphosphorylation, oxidative stress, and neuroinflammation. However, the underlying mechanism of AD remains unclear, and no curative treatment currently exists. The aim was to investigate the effect of thymoquinone by suppressing the RAGE/NOX4 pathway in AD. Mice (n = 60) were divided into five groups, and an experimental AD model induced by an Aβ_1–42 peptide was established in two groups. We also administered 5 mg/kg thymoquinone (TMQ) to the mice for its properties to slow or treat neurodegeneration in AD. Behavioral tests for memory and emotional states, micro-computed tomography (Micro CT) to assess brain volume, ELISA to measure malondialdehyde (MDA) levels, hematoxylin and eosin staining (H&E) to evaluate neuronal degeneration were used. Immunohistochemical (IHC), Western blot (WB), and real-time polymerase chain reaction (PCR) methods were used to evaluate the inhibitory effect of TMQ on a receptor for advanced glycation end products (RAGE)/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) signaling in AD. The results showed that TMQ may have ameliorative effects on memory, spatial learning, learning ability, and anxiety in AD. We showed that TMQ has an antioxidative effect by decreasing MDA levels by the ELSIA method (p < 0.05). There was a marked increase in neuronal degeneration in AD mice compared to other groups (p < 0.05). We concluded that TMQ could ameliorate neuronal degeneration in AD by H&E staining and suppress RAGE/NOX4 signaling by IHC and WB analysis. We concluded that TMQ could be therapeutic in AD by reducing AB expression level by IHC analysis (p < 0.05). Real-time PCR analysis showed that APP (p < 0.05), RAGE, and NOX4 (p < 0.05) gene expressions could be reduced by TMQ. In conclusion, TMQ has a high therapeutic potential in AD and an effective preventive and therapeutic strategy can be developed with more comprehensive studies on TMQ. Full article

Background/Objectives: Vulnerable coronary plaques are strongly associated with acute coronary events, posing significant therapeutic challenges despite statin therapy. This case report evaluates the impact of Evolocumab, a PCSK-9 inhibitor, on stabilizing high-risk plaques and promoting phenotypic transformation, assessed through coronary CT angiography (CCTA). Methods: A 50-year-old male with chronic coronary syndrome and a history of myocardial infarction underwent a CCTA, revealing a high-risk plaque (approximately 50%) in the proximal LAD. Despite achieving LDL-C targets with statin therapy, the plaque showed vulnerability features. Evolocumab (140 mg subcutaneously every two weeks) was added to therapy, combined with dietary counseling and dual antiplatelet therapy. Results: A follow-up CCTA at 24 months demonstrated significant reductions in plaque volume and positive remodeling, with a transformation from a mixed phenotype to a predominantly calcified plaque. LDL-C levels decreased from 71 mg/dL to 18 mg/dL. The patient remained asymptomatic, with no cardiovascular events reported during the follow-up. Conclusions: This case highlights the role of PCSK-9 inhibitors in stabilizing high-risk plaques, achieving structural changes that promote stability beyond LDL-C reduction. Advanced imaging techniques such as CCTA proved essential for risk stratification and monitoring therapy efficacy. Evolocumab offers a promising adjunctive treatment for high-risk patients unsuitable for elective revascularization, potentially redefining the standard of care for plaque stabilization in this setting. Full article

Background: Influenza is a highly contagious respiratory disease that poses significant health and economic burdens. Mice are commonly used as animal models for studying influenza virus pathogenesis and the development of vaccines and drugs. However, the viral volume used for nasal inoculation varies substantially in reported mouse influenza infection models, and the appropriate viral dose is crucial for reproducing experimental results. Methods: Mice were inoculated with mouse lung-adapted strains of influenza virus A/Puerto Rico/8/34 (H1N1) via intranasal administration of 10 μL, 20 μL, and 40 μL at doses of 200 plaque-forming units (PFU) and 2000 PFU. This study investigated the impact of varying viral inoculum volumes on murine outcomes at identical doses and assessed the disparities across diverse dosage levels. Results: Regarding weight change trajectories, mortalities, lung tissue viral titers, and pathological manifestations, the group that received the 40 μL inoculation volume within the low-dose infection mice (200 PFU) manifested a statistically significant divergence from those inoculated with both the 10 μL and 20 μL volumes. Within the context of high-dose infections (2000 PFU), groups that received inoculation volumes of 20 μL and 40 μL exhibited marked disparities when compared to those receiving the 10 μL volume. Conclusions: Disparities in inoculation volume, even under uniform infection dosages, engender differential outcomes in pathogenicity. Of particular note, the viral replication efficacy at a 20 μL inoculation volume demonstrates conspicuous fluctuations across diverse infection dose regimens. Full article

People with HIV (PWH) have a high risk of coronary artery disease (CAD). Cytomegalovirus (CMV) co-infection is very common in PWH, but little is known about its association with CAD. We aimed to investigate if CMV IgG serostatus and concentrations are associated with CAD in PWH. From the Copenhagen Comorbidity in HIV Infection (COCOMO) Study we included PWH with coronary CT angiography (CCTA) and quantitative CMV IgG concentration measurements. We measured the stenosis grades and plaque volumes in the coronary vessels. Using multivariable regressions adjusted for traditional CAD risk factors, we investigated if CMV IgG serostatus and concentrations were associated with any atherosclerosis, obstructive CAD, or plaque volumes. We included 620 PWH of whom 586 had positive CMV serostatus, which was not associated with any atherosclerosis, obstructive CAD, or plaque volumes. A doubling of CMV IgG concentrations was associated with any atherosclerosis (OR 1.21 [95% CI: 1.06–1.39]), obstructive CAD (OR 1.31 [95% CI: 1.07–1.59]), and higher total plaque volume (1.56 [95% CI: 1.21–2.01] fold increase), but the association did not remain significant after adjustment for traditional CAD risk factors. This indicates that CMV IgG serostatus and concentrations are not independently associated with prevalent CAD in PWH. Full article

Background: Cardiovascular disease is one of the leading causes of death around the globe. Atherosclerosis, a chronic inflammatory blood vessel disease that takes years to develop, is its primary cause. Instability and further plaque buildup are caused by chronic inflammation, which creates the conditions for possible rupture. The visualization of arterial lesions in situ can enhance understanding of atherosclerosis progression and potentially improve experimental therapies. Conventional histology methods for assessing atherosclerotic lesions are robust but are destructive and may prevent further tissue analysis. Objectives: The objective of the current study was to evaluate a novel, nondestructive method for the visualization and characterization of atherosclerotic lesions. Methods and Results: Thus, we tested the hypothesis that MRI paired with an iodine-based radiopaque stain would effectively characterize atherosclerotic plaques in a manner comparable to routine histology while maintaining sample integrity and providing whole-volume data. Full article

Emerging evidence from observational studies suggests that lifestyle modifications, particularly moderate-intensity exercise, may confer neuroprotective benefits against dementia, potentially by enhancing brain resistance through clearance mechanisms. Using light-sheet fluorescence microscopy (LSFM) with tissue clearing, we investigated the role of voluntary swimming in ameliorating β-amyloid pathology in a transgenic Alzheimer’s disease (AD) mouse model. Twenty 52-week-old hAPPsw mice were randomly divided into a 5-week voluntary swimming intervention group and a control group (each n = 10). Each session included a 10-min swim followed by a 10-min rest, escalating from one session per day in the first week to three sessions per day by the fifth week. The excised brains were prepared using tissue-clearing and volume immunostaining with thioflavin-S for β-amyloid. For LSFM imaging, the individual plaque area and volume, total plaque load, and morphological parameters were quantified via an Imaris-based three-dimensional (3D) volumetric surface model. Visual comparison revealed that the intervention group presented significantly lower β-amyloid accumulation. The total surface volume of β-amyloid accumulation in the intervention group was significantly lower than that of the control group (intervention, 122,180,948 μm³ [105,854,660–169,063,081]; control, 167,201,016 μm³ [139,367,765–193,535,450]; p = 0.043). There were no significant differences in the morphological parameters, such as ellipticity and sphericity. Our LSFM study demonstrated notable reductions in β-amyloid, as evidenced by a decrease in total surface volume, in 52-week-old transgenic mice after a 5-week structured swimming program, supporting the notion that even in advanced AD stages, leisure-time voluntary swimming serves as an efficacious intervention for augmenting resistance to pathology. Full article

Background/Objectives: Dual-layer stents (DLS) with micromesh technology may offer better protection from plaque protrusion compared to single-layer stents (SLS), but little data are available. The aim of this study is to compare clinical outcomes of elective carotid artery stenting for asymptomatic and symptomatic patients treated for primary CAS with DLS or SLS in a high-volume center. Methods: This study is a single-center retrospective cohort study and included patients who underwent elective CAS between December 2006 and September 2023. The final analysis included patient baseline characteristics, postoperative complications and patient outcomes. Results: A total of 573 patients underwent elective carotid artery stenting in the study period. Most of the 573 patients undergoing CAS were male (62.5%), and the median age of patients at the time of CAS was 70 years. Of the 573 eligible patients, 43.5% (n = 249) were asymptomatic and 56.4% (n = 323) were symptomatic. Analyzing neurological complications, it was found that the only factor that had a statistically significant effect was the type of stent used. Patients who had a carotid stenting procedure using a single-layer carotid stent had statistically significantly more periprocedural neurological complications (8.3% (n = 35)) than the double-mesh stent group (2% (n = 3)), mostly due to more transient ischemic attacks in the single-layer stent group (4% (n = 17)) compared to the double-mesh group (0.7% (n = 1)). Conclusions: The use of carotid double-layer stents is associated with a low rate of periprocedural and postprocedural events. Full article

Impaired glucose tolerance (IGT), a prediabetic state, is a known risk factor for coronary artery disease (CAD). Low-attenuation plaque (LAP) lesions are associated with a high risk of coronary events. We aimed to evaluate high-risk plaque characteristics in LAP lesions between patients with IGT and normal glucose tolerance (NGT) in patients suspected for stable CAD. Coronary computed tomography angiography (CCTA) identified LAP lesions and assessed plaque volumes, burdens, and high-risk plaque features. Glycemic tolerance was stratified using oral glucose tolerance tests. Among 148 patients, 202 LAP lesions were identified, with 93 patients classified as NGT and 55 as IGT. Patients with IGT had a significantly higher prevalence of LAP lesions compared with NGT (p = 0.007). LAP volume was higher in IGT (16.46 ± 12.52 mm³) compared with NGT (12.66 ± 9.72 mm³, p = 0.01), but this association did not persist in multivariate analysis. The LAP burden was greater in IGT (10.79 ± 6.84%) than NGT (8.62 ± 5.93%, p = 0.02), and the napkin-ring sign was more frequent in IGT (12%) versus NGT (5%, p = 0.02); these associations remained significant in multivariate analysis. Patients with IGT had a higher LAP burden and higher frequency of napkin-ring signs. These findings may help explain the common occurrence of prediabetes in patients with acute myocardial infarction. Full article

Fractional flow reserve (FFR) has been well validated as a modality for evaluating myocardial ischemia, demonstrating the superiority of FFR-guided percutaneous coronary intervention (PCI) over conventional angiography-guided PCI. As a result, the strategy for coronary artery bypass grafting (CABG) is shifting toward FFR guidance. However, the advantage of FFR-guided CABG over angiography-guided CABG remains unclear. While FFR-guided CABG can help avoid unnecessary grafting in cases of moderate stenosis, it may also carry the risk of incomplete revascularization. The limited use of FFR due to the need for hyperemia has led to the development of non-hyperemic pressure ratios (NHPRs). NHPR pullback provides trans-stenotic pressure gradients, which may offer valuable insights for CABG strategies. Recently, computed tomographic coronary angiography (CTCA) has emerged as a non-invasive modality that provides accurate data on lesion length, diameter, minimum lumen area, percentage stenosis, and the volume and distribution of high-risk plaques. With the introduction of FFR-CT, CTCA is now highly anticipated to provide both functional evaluation (of myocardial ischemia) via FFR-CT and anatomical information through serial quantitative assessment. Beyond the diagnostic phase, CTCA, augmented by automatic artificial intelligence, holds great potential for guiding therapeutic interventions in the future. Full article

Aim: The aim of this study was to evaluate the differences in plaque composition and burden between normal glycemic status (NGS) and dysglycemia expressed as impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). Methods: Clinically indicated coronary computed tomography angiography was used to evaluate patients with suspected coronary artery disease (CAD). An oral glucose tolerance test was performed to assess glycemic status. Patients were stratified as NGS, IGT, and T2DM. Plaque volumes were quantified using validated software, with further compositional measurements of low-attenuation, non-calcified, and calcified plaque burden. Results: Of 355 patients with suspected CAD, 220 had NGS, 92 were diagnosed with IGT, and 43 with known T2DM. Low-attenuation plaque volume was significantly higher in IGT (209 mm³, p < 0.02) and T2DM (243 mm³, p = 0.005) compared with NGS (166 mm³). Total plaque burden was similar between all groups, but a significantly greater low-attenuation plaque burden was seen in IGT (p = 0.03) and T2DM (p = 0.02) compared with NGS. The multivariate linear regression model adjusted for clinical risk factors showed that patients with IGT had a greater low-attenuation plaque burden compared with those with NGS (p = 0.03). Interestingly, no significant differences in plaque burdens were observed between those with IGT and T2DM in both univariate and multivariate analyses. Conclusions: Dysglycemia, including impaired glucose tolerance and type 2 diabetes mellitus, was associated with increased low-attenuation plaque burden compared with normal glycemic status. Patients with IGT demonstrated plaque burden similar to patients with known T2DM, underscoring the need for early metabolic intervention. Full article

The growing threat of antimicrobial resistance (AMR), exacerbated by the COVID-19 pandemic, highlights the urgent need for alternative treatments such as bacteriophage (phage) therapy. Phage therapy offers a targeted approach to combat bacterial infections, particularly those resistant to conventional antibiotics. This study aimed to standardize an agar plate method for high-mix, low-volume phage production, suitable for personalized phage therapy. Plaque assays were conducted with the double-layer agar method, and plaque sizes were precisely measured using image analysis tools. Regression models developed with Minitab software established correlations between plaque size and phage production, optimizing production while minimizing resistance development. The resulting Plaque Size Calculation (PSC) model accurately correlated plaque size with inoculum concentration and phage yield, establishing specific plaque-forming unit (PFU) thresholds for optimal production. Using phages targeting pathogens such as Escherichia, Salmonella, Staphylococcus, Pseudomonas, Chryseobacterium, Vibrio, Erwinia, and Aeromonas confirmed the model’s accuracy across various conditions. The model’s validation showed a strong inverse correlation between plaque size and minimum-lawn cell clearing PFUs (MCPs; R² = 98.91%) and identified an optimal inoculum density that maximizes yield while minimizing the evolution of resistant mutants. These results highlight that the PSC model offers a standardized and scalable method for efficient phage production, which is crucial for personalized therapy and AMR management. Furthermore, its adaptability across different conditions and phages positions it as a potential standard tool for rapid and precise phage screening and propagation in both clinical and industrial settings. Full article