Search Results (52,690)

The use of non-vitamin K antagonist oral anticoagulants (NOACs) has brought a significant progress in the management of cardiovascular diseases, considered clinically superior to vitamin K antagonists (VKAs) particularly in the prevention and treatment of thromboembolic events. In addition, numerous advantages such as fixed dosing, lack of laboratory monitoring, and fewer food and drug-to-drug interactions make the use of NOACs superior to VKAs. While NOACs are synthetic drugs prescribed for specific conditions, nattokinase (NK) is a natural enzyme derived from food that has potential health benefits. Various experimental and clinical studies reported the positive effects of NK on the circulatory system, including the thinning of blood and the dissolution of blood clots. This enzyme showed not only fibrinolytic activity due to its ability to degrade fibrin, but also an affinity as a substrate for plasmin. Recent studies have shown that NK has additional cardioprotective effects, such as antihypertensive and anti-atherosclerotic effects. In this narrative review, we presented the cardioprotective properties of two different approaches that go beyond anticoagulation: NOACs and NK. By combining evidence from basic research with clinical findings, we aim to elucidate the comparative cardioprotective efficacy of these interventions and highlight their respective roles in modern cardiovascular care. Full article

Turkey Hemorrhagic Enteritis (THE) is an acute disease caused by a Siadenovirus that affects 4 week-aged and older turkeys, characterized by acute depression, bloody droppings, and a high mortality rate. The immunosuppressive attributes of THE can protract disease progression and create a predisposition in birds towards subsequent bacterial infectiodoralns involving Escherichia coli and Clostridium perfringens (necrotic enteritis). Turkey Hemorrhagic Enteritis Virus (THEV) predominantly affects turkeys and carries substantial economic implications for this industry. Macrophages and B lymphocytes are recognized as the predominant target cells for the virus, while the spleen is the principal site of viral replication. Infected cells have also been observed in various other tissues, including the intestines, bursa of Fabricius, cecal tonsils, thymus, liver, kidney, peripheral blood leukocytes, and lungs. The economic relevance of this disease is derived both from the high mortality rate, which can reach 60% depending on the virulence of the strain, and from subclinical disease responsible for poor performance in vaccinated animals. This review aims to provide a comprehensive overview of THE, spanning etiology, epidemiology clinical signs and gross lesions, prevention, and management. Full article

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease leading to progressive demyelination and neuronal loss, with extensive neurological symptoms. As one of the most widespread neurodegenerative disorders, with an age onset of about 30 years, it turns out to be a socio-health and economic issue, thus necessitating therapeutic interventions currently unavailable. Loss of integrity in the blood–brain barrier (BBB) is one of the distinct MS hallmarks. Brain homeostasis is ensured by an endothelial cell-based monolayer at the interface between the central nervous system (CNS) and systemic bloodstream, acting as a selective barrier. MS results in enhanced barrier permeability, mainly due to the breakdown of tight (TJs) and adherens junctions (AJs) between endothelial cells. Specifically, proinflammatory mediator release causes failure in cytoplasmic exposure of junctions, resulting in compromised BBB integrity that enables blood cells to cross the barrier, establishing iron deposition and neuronal impairment. Cells with a compromised cytoskeletal protein network, fiber reorganization, and discontinuous junction structure can occur, resulting in BBB dysfunction. Recent investigations on spatial transcriptomics have proven circularRNAs (circRNAs) to be powerful multi-functional molecules able to epigenetically regulate transcription and structurally support proteins. In the present review, we provide an overview of the recent role ascribed to circRNAs in maintaining BBB integrity/permeability via cytoskeletal stability. Increased knowledge of the mechanisms responsible for impairment and circRNA’s role in driving BBB damage and dysfunction might be helpful for the recognition of novel therapeutic targets to overcome BBB damage and unrestrained neurodegeneration. Full article

Purpose: Physical activity induces numerous modifications in the morphological, rheological, and biochemical properties of blood. The purpose of this study was to evaluate changes in blood rheological and biochemical indicators among runners. Also, we assessed how the rheological and biochemical properties of blood in people who practised running characterised the range and direction of exercise modifications and allowed for the diagnosis of transient adaptive effects. Methods: This study included 12 athletes who regularly trained in middle- and long-distance running (6–8 times a week) and presented a high sports level (national and international class). The athletes performed a 30 min warm-up consisting of 15 min of jogging and exercises. After a 10 min rest, they completed a 3 km run with submaximal effort. Blood samples were collected at baseline and after the effort. Results: No statistically significant changes were revealed in erythrocyte, leukocyte, platelet, iron, ferritin, transferrin, erythropoietin, or C-reactive protein concentrations in the examined runners. The same applied to the elongation index at a shear stress within the range of 0.30–60.00 Pa, amplitude and total extent of aggregation, aggregation half-life, and aggregation index. A significant increase (within standard limits) was only observed in fibrinogen concentration after running. Conclusions: The lack of post-exercise changes in blood rheological and biochemical indicators in the investigated runners points at an efficient haemorheological system. This, in turn, reflects well-executed training and remarkably well-trained adaptive systems responsible for regeneration. Full article

Immunotherapy has revolutionized the treatment of myeloid oncologic diseases, particularly for patients resistant to chemotherapy or ineligible for allogeneic stem cell transplantation due to age or fitness constraints. As our understanding of the immunopathogenesis of myeloid malignancies expands, so too do the treatment options available to patients. Immunotherapy in myeloid malignancies, however, faces numerous challenges due to the dynamic nature of the disease, immune dysregulation, and the development of immune evasion mechanisms. This review outlines the progress made in the field of immunotherapy for myeloid malignancies, addresses its challenges, and provides insights into future directions in the field. Full article

Background/Objectives: The demographic shift towards an aging population necessitates a reevaluation of surgical interventions like coronary artery bypass grafting (CABG) in octogenarians. This study aims to elucidate the outcomes of CABG in octogenarians with heart failure and reduced ejection fraction (HFrEF), a group traditionally considered at high risk for such procedures. Methods: Conducted across four academic hospitals in Germany from 2017 to 2023, this retrospective multicenter study assessed 100 patients (50 octogenarians ≥80 years and 50 non-octogenarians <80 years) with HFrEF undergoing isolated CABG. Through propensity score matching, the study aimed to compare the incidence of major adverse cardiac and cerebrovascular events (MACCEs), as well as other clinical endpoints, between the two groups. Statistical analyses included chi-square, ANOVA, Mann–Whitney U test, Cox regression, and logistic regression, aiming to identify significant differences in outcomes. Results: The study revealed no significant difference in the combined incidence of MACCEs between octogenarians and non-octogenarians (OR: 0.790, 95% CI: 0.174–3.576, p = 0.759). Mortality rates were similar across groups (7% each, p = 1.000), as were occurrences of postoperative myocardial infarction (2% each, p = 1.000) and stroke (3% total). Secondary outcomes like delirium (17% total, no significant age group difference, p = 0.755), acute kidney injury (18% total, p = 0.664), and the need for dialysis (14% total, p = 1.000) also showed no differences between age groups. Interestingly, non-octogenarians required more packed red blood cells during their stay (p = 0.008), while other postoperative care metrics, such as hospital and ICU length of stay and ventilation hours, were comparable across groups. Conclusion: This multicenter study highlights that CABG is a viable and safe surgical option for octogenarians with HFrEF, challenging prior assumptions about the elevated risks associated with performing this procedure in older patients. The absence of significant differences in the incidence of MACCEs and other postoperative complications across age groups emphasizes the importance of careful patient selection and perioperative management. These findings advocate for a more inclusive approach to surgical treatment for octogenarians with HFrEF, suggesting that age alone should not be a determinant for CABG eligibility. This study contributes critical insights into optimizing care for a high-risk demographic, indicating a need for tailored guidelines that accommodate the aging population with complex cardiac conditions. Full article

Background and Objectives: Genomic studies have identified several SNP loci associated with schizophrenia in East Asian populations. Environmental factors, particularly urbanization, play a significant role in schizophrenia development. This study aimed to identify schizophrenia susceptibility loci and characterize their biological functions and molecular pathways in Taiwanese urban Han individuals. Materials and Methods: Participants with schizophrenia were recruited from the Taiwan Precision Medicine Initiative at Tri-Service General Hospital. Genotype–phenotype association analysis was performed, with significant variants annotated and analyzed for functional relevance. Results: A total of 137 schizophrenia patients and 26,129 controls were enrolled. Ten significant variants (p < 1 × 10⁻⁵) and 15 expressed genes were identified, including rs1010840 (SOWAHC and RGPD6), rs11083963 (TRPM4), rs11619878 (LINC00355 and LINC01052), rs117010638 (AGBL1 and MIR548AP), rs1170702 (LINC01680 and LINC01720), rs12028521 (KAZN and PRDM2), rs12859097 (DMD), rs1556812 (ATP11A), rs78144262 (LINC00977), and rs9997349 (ENPEP). These variants and associated genes are involved in immune response, blood pressure regulation, muscle function, and the cytoskeleton. Conclusions: Identified variants and associated genes suggest a potential genetic predisposition to schizophrenia in the Taiwanese urban Han population, highlighting the importance of potential comorbidities, considering population-specific genetic and environmental interactions. Full article

Automated milking systems (AMS) are increasingly adopted for dairy cow production, promoting individualized cow management dependent on factors like lactation stage, age, and productivity. The study objective was to investigate the effects of early lactation milking frequency on cows milked via AMS. Multiparous Holstein cows blocked by parity and due date were randomly assigned to treatments (n = 8 per treatment): three (3X) or six (6X) milkings per day (MPD). The experimental phase (EXP) was defined as 4 to 29 days in milk (DIM). The AMS settings were programed so 3X cows were limited to three MPD while 6X cows were allowed six MPD. Afterwards was the carry over phase (CO) ranging from 30 to 90 DIM; all cows were allowed up to six MPD. Measurements by the AMS included bodyweight, milk yield (MY), and pellet intake. Weekly composite milk samples were analyzed for macronutrient composition and fatty acid (FA) profile. Coccygeal blood was sampled at 3, 8 ± 1, and 13 ± 1 DIM; concentrations of blood plasma analytes were quantified. Greater MPD was achieved for 6X cows versus 3X cows during EXP, but similar during the CO. Daily MY was non-separable during the EXP while 6X cows in their third or greater lactation group (3 + LG) had greater MY than 3X cows of the same LG during the CO. Milk fat content and 4% fat-corrected MY were both greater for 6X, 3 + LG cows during the EXP compared to 3X, 3 + LG cows. Milk FA methyl esters (FAME) proportions were different between MPD groups, with 6X, 3 + LG cows having the lowest short, even-chain FA from de novo or post-absorptive origin. Differences in analytes indicated that 6X, 3 + LG cows experienced metabolic stress and incorporated greater FA from adipose tissue. Greater early lactation MPD in AMS may shift cow nutrient partitioning to support greater production in 3+ parity cows. Full article

Rapid and reliable Rhesus D typing is crucial for blood donation centers. In instances of massive blood transfusion or reduced antigen expression, DNA-based phenotype prediction becomes mandatory. Our molecular RHD typing approach involves an initial real-time PCR for the most common aberrant RHD types in our region, RHD*01W.1 (weak D type 1), RHD*01W.2 (weak D type 2), RHD*01W.3 (weak D type 3), and RHD*07.01 (DVII). For comprehensive coverage, Sanger sequencing of RHD coding regions is performed in the case of PCR target-negative results. We evaluated the specificity and accuracy of these methods using the recently launched LightCycler^® PRO real-time platform. All findings demonstrated remarkable accuracy. Notably, the LightCycler^® PRO instrument offers a distinct advantage in data interpretation and integration via the HL7 interface. This study underlines the importance of including advanced molecular techniques in blood typing protocols, especially in scenarios where conventional serological methods may be insufficient. Full article

Rickettsiae are an interesting group of bacteria comprising a large number of obligate intracellular species. The circulation of these bacteria in the environment depends on the presence of vectors (blood-sucking invertebrates) and their hosts. On the basis of phylogenetic analyses in 2022, a division into five groups of Rickettsia has been proposed: I belli group, II canadensis group, III typhus group, and IV and V spotted group fever (respectively II, phylogenetically older, and I). The genus Rickettsia includes species that are both pathogenic and nonpathogenic to humans and domestic and wild animals. Some Rickettsia species are invertebrate symbionts. Currently, rickettsiae, which are transmitted mainly by ticks, are spreading worldwide. This has been promoted by climate change, environmental changes caused by humans, and the synanthropisation of plants and animals. Therefore, it is extremely important to monitor the natural and urban environments. The study of potential vectors and reservoirs of bacteria in the genus Rickettsia should be a permanent part of the analysis of the modern human environment. Full article

Type 1 Gaucher disease (GD1) is a rare, autosomal recessive disorder caused by glucocerebrosidase deficiency. Skeletal manifestations represent one of the most debilitating and potentially irreversible complications of GD1. Although imaging studies are the gold standard, early diagnostic/prognostic tools, such as molecular biomarkers, are needed for the rapid management of skeletal complications. This study aimed to identify potential protein biomarkers capable of predicting the early diagnosis of bone skeletal complications in GD1 patients using artificial intelligence. An in silico study was performed using the novel Therapeutic Performance Mapping System methodology to construct mathematical models of GD1-associated complications at the protein level. Pathophysiological characterization was performed before modeling, and a data science strategy was applied to the predicted protein activity for each protein in the models to identify classifiers. Statistical criteria were used to prioritize the most promising candidates, and 18 candidates were identified. Among them, PDGFB, IL1R2, PTH and CCL3 (MIP-1α) were highlighted due to their ease of measurement in blood. This study proposes a validated novel tool to discover new protein biomarkers to support clinician decision-making in an area where medical needs have not yet been met. However, confirming the results using in vitro and/or in vivo studies is necessary. Full article

Endobronchial ultrasound (EBUS) is used in the minimally invasive sampling of thoracic lymph nodes. In lung cancer staging, the accurate assessment of mediastinal structures is essential but challenged by variations in anatomy, image quality, and operator-dependent image interpretation. This study aimed to automatically detect and segment mediastinal lymph nodes and blood vessels employing a novel U-Net architecture-based approach in EBUS images. A total of 1161 EBUS images from 40 patients were annotated. For training and validation, 882 images from 30 patients and 145 images from 5 patients were utilized. A separate set of 134 images was reserved for testing. For lymph node and blood vessel segmentation, the mean ± standard deviation (SD) values of the Dice similarity coefficient were 0.71 ± 0.35 and 0.76 ± 0.38, those of the precision were 0.69 ± 0.36 and 0.82 ± 0.22, those of the sensitivity were 0.71 ± 0.38 and 0.80 ± 0.25, those of the specificity were 0.98 ± 0.02 and 0.99 ± 0.01, and those of the F1 score were 0.85 ± 0.16 and 0.81 ± 0.21, respectively. The average processing and segmentation run-time per image was 55 ± 1 ms (mean ± SD). The new U-Net architecture-based approach (EBUS-AI) could automatically detect and segment mediastinal lymph nodes and blood vessels in EBUS images. The method performed well and was feasible and fast, enabling real-time automatic labeling. Full article

This study evaluates the antimicrobial efficacy of chitosan nanoparticles (CNPs), varying in size, against clinical isolates of Mycobacterium tuberculosis (MTB), E. coli, S. aureus, E. faecalis, and C. albicans, as well as the antimicrobial effects of aqueous extracts and lyophilized powders of Allium (garlic) species. CNPs were synthesized through ionotropic gelation and characterized by Z potential, hydrodynamic diameter (dynamic light scattering, DLS), and SEM. Aqueous garlic extracts were prepared via decoction. We assessed antimicrobial activity using disk diffusion and broth microdilution methods; in addition, a modified agar proportion method in blood agar was used for antimicrobial activity against MTB. CNPs inhibited MTB growth at 300 μg for 116.6 nm particles and 400 μg for 364.4 nm particles. The highest antimicrobial activity was observed against E. faecalis with nanoparticles between 200 and 280 nm. Allium sativum extract produced inhibition for C. albicans at 100 μg. The results indicate that CNPs possess significant antimicrobial properties against a range of pathogens, including MTB, at high concentrations. On the other hand, aqueous Allium sativum extracts exhibited antimicrobial activity. Nonetheless, due to their instability in solution, the use of lyophilized Allium sativum powder is preferable. Full article

While pulse oximetry using remote photoplethysmography (rPPG) is used in medicine and consumer health, sound theoretical foundations for this methodology are not established. Similarly to traditional pulse oximetry, rPPG oximetry uses two wavelengths to calculate the tissue oxygenation using the so-called ratio-of-ratios, R. However, the relationship between R and tissue oxygenation has not been derived analytically. As such, rPPG oximetry relies mostly on empirical methods. This article aimed to build theoretical foundations for pulse oximetry in rPPG geometry. Using the perturbation approach in diffuse approximation for light propagation in tissues, we obtained an explicit expression of the AC/DC ratio for the rPPG signal. Based on this ratio, the explicit expression for “ratio-of-ratios” was obtained. We have simulated the dependence of “ratio-of-ratios” on arterial blood saturation across a wide range (SaO2 = 70–100%) for several commonly used R/IR light sources (660/780, 660/840, 660/880, and 660/940 nm) and found that the obtained relationship can be modeled by linear functions with an extremely good fit (R² = 0.98–0.99) for all considered R/IR pairs. Moreover, the location of the pulsatile volume can be extracted from rPPG data. From experimental data, we found that the depth of blood pulsations in the human forehead can be estimated as 0.6 mm on the arterial side, which points to the papillary dermis/subpapillary vascular plexus origin of the pulsatile volume. Full article

To test the hypothesis that they serve as systemic biomarkers of chronic obstructive pulmonary disease (COPD), we profiled the mRNA expression of enzymes connected to systemic inflammation and GSH metabolism in peripheral blood mononuclear cells (PBMCs). These were taken from patients displaying acute exacerbation of COPD (AE-COPD) and stable COPD, and also from non-obstructive smokers and non-smokers. The expression of poly(ADP-ribose) polymerase-1 was increased, but that of histone deacetylase 2 was decreased in association with AE-COPD. The expression of modulatory subunit of glutamyl–cysteine ligase was higher and that of its catalytic subunit, together with the expression of dipeptidyl peptidase 4, was lower in COPD patients compared with non-obstructive smokers and non-smokers. Leukotriene A4 hydrolase saw increased expression in patients with COPD according to disease severity compared to non-obstructive individuals, whereas the expression of GSH peroxidase increased in non-obstructive smokers and COPD patients with the growing number of pack-years smoked. The results corroborate COPD and its acute exacerbation as a complex systemic disorder demonstrating distinct associations with the expression of enzymes linked to inflammation and the regulation of GSH metabolism. Full article