Stress is an inherent sensation of being unable to handle demands and occurrences. If not properly managed, stress can develop into a chronic condition, leading to the onset of additional chronic health issues like cardiovascular illnesses and diabetes. Various stress meters have been suggested in the past, along with diverse approaches for its estimate. However, in the case of more serious health issues such as hypertension and diabetes, the results can be significantly improved. This study presents the design and implementation of a distributed wearable sensor computing platform with multiple channels. The platform aims to estimate stress levels in diabetes patients by utilizing a fuzzy logic algorithm that is based on the assessment of several physiological indicators. Additionally, a mobile application was created to monitor users' stress levels and integrate data on their blood pressure and blood glucose levels. Validation experiments were performed on patients with chronic diabetes, and the initial findings are presented in the study.

We estimated the risk of blood clots after COVID-19 vaccination accounting for the roles of vaccination in reducing the infection rate, and indirectly lowering the risk of blood clots caused by infection. A self-controlled case series method was used to examine the association between blood clots and COVID-19 vaccination. To deal with the bias due to under-reported infection among non-hospitalized subjects, a case-control study was used to compare the risk of blood clots in infected subjects to control subjects who were hospitalized due to physical injury. We found increased risks of blood clots after vaccination (incidence rate ratio is 1.13, 95% confidence interval (CI): [1.03, 1.24] after the first dose and 1.23, 95% CI: [1.13,1.34] after the second dose). Furthermore, vaccination attenuated the increased risk of blood clots associated with infection (odds ratio (OR) = 2.16, 95% CI: [1.93, 2.42] in unvaccinated versus OR=1.46, 95% CI: [1.25, 1.70] in vaccinated). A causal model was used to explain and weigh up possible risk factors for blood clots after COVID-19 vaccination. After accounting for vaccine efficacy against infection and the protection against infection-associated blood clots, receiving the COVID-19 vaccines decreases the risk of blood clots, especially during high infection rate period.

World Health Organization recommends adjusting the salt intake as a part of the nine global targets to reduce premature mortality from non-communicable chronic diseases as priority and most cost-effective intervention. In 2006. the main aim of the Croatian Action on Salt and Health was to decrease salt intake for 16% because of its critical intake and consequences on human health. We have organized educative activities for increasing awareness on salt harmfulness, defined food categories of prime interest, collaborate with industries and determine salt intake (24h urine-sodium excretion). It was determined that the proportion of salt in ready-to-eat baked bread should not exceed 1.4%. In the period 2014 –2022, salt in the semi-white bread was reduced 14%, in bakery 22% and in largest meat industry in Croatia 25%. Awareness of the harmfulness of salt on health increased from 65.3% in 2008 to 96.9% in 2023 and salt intake was reduced 15.9%-1.8 grams/day (22.8% men, 11.7% women). In last 18 years a significant decrease in salt intake was achieved in Croatia, awareness of its harmfulness increased, collaboration with food industry established and regulatory documents launched. However, salt intake is still very high underlying the need for continuation of efforts and even stronger activities.

Background: In past years recreational diving has attracted more and more interest and among such divers an increasing number of diabetic divers. However, there is limited research on the accuracy of CGM systems under hyperbaric conditions and consistently diving guidelines make little reference to the use of CGM. Subject and Method: This exploratory study collected blood glucose samples of one diabetic diver over four dives and assessed the deviation of intersitial glucose values from two CGM systems based on 33 samples. A notable step of this method is to collect the data from actual dives under water. Results: The results indicate that a) under hyperbaric conditions of up to 2bar additional pressure and b) after decompression both CGM systems work comparably accurate as indictated by the manufacturer under normal conditions. This has been checked in terms of MARD and Clarke Error Grid Distirbution. Conculsion: For diabetic divers the results suggest they may take CGM monitors with them on dives to react to potential hypoglycemic events before they occur, i.e. when it is still safe to supplement glucose. For dive guidelines the results imply that these could reference CGM for dive planning and monitoring during the dive to increase divers‘ safety. For research this exploratory confirms the current hypothesis that neither increased pressure nor saltwater have an effect on blood glucose and the functioning of CGM systems. Further research may include additional sampling (number and depth) and more elaborate blood glucose measurement. The experimental setup applied is an efficient way to test further CGM systems.

KLEPTOSE® CRYSMEB is a methylated cyclodextrin derivative displaying less methylated group substitution than randomly methylated cyclodextrin. It has demonstrated an impact on atherosclerosis and neurological diseases. linked in part to cholesterol complexation and immune response, but the impact on inflammatory cascade pathways was not clear. Thus, the impact of KLEPTOSE® CRYSMEB on various pharmacological targets was assessed using human umbilical vein endothelial cells in physiological and inflammatory conditions, followed by screening against twelve human primary cell-based systems designed to model complex human tissue and disease biology of the vasculature, skin, lung, and inflammatory tissues using the BioMAP® Diversity PLUS® Panel. Finally, the anti-inflammatory mechanism was investigated on peripheral blood mononuclear cells to evaluate anti-inflammatory or pro-resolving properties. The results showed that KLEPTOSE® CRYSMEB can modulate the immune system in vitro and potentially manage vascular issues by stimulating the expression of molecules involved in the crosstalk between immune cells and other cell types. It showed anti-inflammatory effects driven by pro-inflammatory cytokine secretion inhibition and could have different impacts on different tissue types. Moreover, this cyclodextrin showed no clear impact on pro-resolving lipid mediators. Finally, it appeared that the mechanism of action of KLEPTOSE® CRYSMEB seems to not be shared by well-known anti-inflammatory molecules.

Objectives: The purpose of this study is to determine the association between umbilical venous blood flow (UVBF) to placental pulsatility index (PPI) ratio and gestational age (GA) in women undergoing prenatal assessments and adverse pregnancy outcome (APO) screening Methods: Between January and December 2022, sonographic examinations were conducted to assess the fetal umbilical cord insertion site in singleton fetuses, and hemodynamic indices of the umbilical artery, umbilical vein, and uterine artery were computed. Through regression analysis, we derived the optimal regression equation to elucidate the UVBF/PPI ratio parameters based on GA. Results: Among 492 singleton fetuses between 21+0 and 40+6 weeks of gestation in the final study. The average fetal UVBF/PPI ratio was 180.45±119.32. Correlation analysis revealed a positive relationship between the UVBF/PPI ratio and GA(p = .000). Using regression analysis, the best-fit regression equation was the linear function model, which explains the value of UVBF/PPI ratio parameters based on GA. Lower UVBF/PPI ratio revealed a positive relationship in the low birth weight fetuses (p=0.021) and higher preterm delivery rate (p=0.034). Cerebroplacental ratio (CPR) showed a high correlation with the UVBF/PPI ratio (r=0.471, p=0.000). Conclusions: The findings of our analyses revealed that contribute to our understanding of fetal hemodynamics and highlight the potential of UVBF/PPI ratio as a predictive marker for adverse pregnancy outcomes, such as preterm birth, low birth weight, or potential fetal hypoxemia. It might be useful for prenatal counseling and clinical purposes.

The platelet count, a component of the full blood count, has been identified as a useful diagnostic marker for cancer in primary care. The reference range for the platelet count is 150 to 400 or 450 × 109/l; this range does not account for natural variation in platelet count by age and sex. This study used three primary care cohorts from England Canada, and Australia. Patients aged 40 years and over with a full blood count were included and stratified by age (in 10-year bands), sex, (male/female), and platelet count group. Cancer incidence within one year of test date was estimated from linked registry data. In all three countries there was a clear upwards trend in cancer incidence with increasing platelet count, for both sexes and at all age groups. Lung and colorectal were the most common sites. These results have important implications for the international application of this work; analysis of local health datasets will be crucial to determine appropriate thresholds. Appropriate upper thresholds will depend on local populations, healthcare needs, and priorities. Further research is needed to assess the likely impact of new recommendations on the healthcare system, on cancer outcomes, and patient benefit.

Non-neural Machine Learning (ML) and Deep Learning (DL) are used to predict system failures in industrial maintenance. However, only a few studies have assessed the effect of varying the amount of past data used to make a prediction and the extension in the future of the forecast. This study evaluates the impact of the size of the reading window and of the prediction window on the performances of models trained to forecast failures in three data sets of (1) an industrial wrapping machine working in discrete sessions, (2) an industrial blood refrigerator working continuously and (3) a nitrogen generator working continuously. A binary classification task assigns the positive label to the prediction window based on the probability of a failure to occur in such an interval. Six algorithms (logistic regression, random forest, support vector machine, LSTM, ConvLSTM and Transformers) are compared using multivariate time series. The dimension of the prediction windows plays a crucial role and the results highlight the effectiveness of DL approaches in classifying data with diverse time-dependent patterns preceding a failure and the effectiveness of ML approaches in classifying similar and repetitive patterns preceding a failure.

COVID-19, caused by the SARS-CoV-2 virus, has spread around the world and killed around 6.9 million people. Rapid and accurate diagnosis is essential for preventing and controlling the disease, reducing transmission and consequently saving lives. RT-PCR is the gold standard test used to detect the disease. However, the test is expensive and the result is time-consuming, which makes mass testing difficult, especially in countries with limited resources. In addition, the test has high analytical specificity and low diagnostic sensitivity, which leads to false-negative results. Several studies in the literature report the presence of hematological and biochemical alterations in infected patients and use these alterations with machine learning algorithms to help diagnose the disease. Therefore, this article presents the results obtained by different neural network architectures based on Adaptive Resonance Theory (ART) for the diagnosis of COVID-19. The study was conducted in two distinct stages: the first consisted of selecting the best ART network among several, using three open-access datasets and comparing the results with the literature. In the second stage, the chosen model was tested on a dataset containing patients from various hospitals in four countries. In addition, the model was subjected to external validation, including data from a country not present during the training and adjustment of the model, in order to validate the robustness and generalization capacity of the model. The results obtained by the ART networks in this study are promising, outperforming not only classical models, but also the deep learning models often used in the literature. Validation on data from different countries strengthens the model’s reliability and effectiveness.

Angiostrongylus cantonensis, a zoonotic parasite, can invade the human central nervous system (CNS) and cause acute eosinophilic meningitis or eosinophilic meningoencephalitis. Mice infected with A. cantonensis show elevated levels of pro-inflammatory cytokines, plasminogen activators, and matrix metalloproteinase-9, resulting in disruption of the blood-brain barrier (BBB) and immune cell infiltration into the CNS. Caveolin-1 (Cav-1) regulates the permeability of the BBB, which affects immune cells and cerebrospinal fluid. This intricate interaction ultimately fuels the progression of brain damage and edema. This study aims to investigate the regulatory role of Cav-1 in the pathogenesis of meningoencephalitis induced by A. cantonensis infection. We investigate pathological alterations by triphenyl-tetrazolium chloride, brain water content, BBB permeability, Western blot analysis, and gelatin zymography in BALB/c mice after A. cantonensis. The study evaluates the critical role of Cav-1 regulation through the TLR4 / MyD88 signaling pathway, modulates tight junction proteins, influences BBB permeability, and contributes to brain damage in A. cantonensis-induced meningoencephalitis.

This study aims to explore the associations between pediatric adverse events (PAEs) and hospital and patient characteristics within the inpatient hospital setting, focusing solely on the framework of pediatric quality indicators (PDIs) from the Agency for Healthcare Research and Quality (AHRQ). Specifically, the study focuses on NQI 03 Neonatal Blood Stream Infection (NBSI). The analysis utilizes discharge data from the Healthcare Cost and Utilization Project (HCUP) Kids’ Inpatient Databases (KID) for the year 2019. Through this analysis, the study seeks to answer research questions regarding associations between hospital characteristics and patient characteristics with NQI 03. The methodology employs bivariate and multivariate logistic regression models to analyze patient-level encounters of NBSI. The results indicate that smaller, rural, and non-teaching hospitals exhibit significantly lower odds of NQI 03 compared to large hospitals. Various individual factors such as gender, age, race, service lines, payment sources, and major operating room procedures also demonstrate differing levels of significance in relation to NQI 03, warranting further investigation. This study provides contextual expansion on the findings and offers valuable insights into PAEs in the inpatient hospital setting, specifically focusing on NBSI within the PDIs framework. It highlights areas for developing evidence-based interventions and guidelines for clinicians and policymakers. Ultimately, the findings contribute to the growing understanding of factors influencing NBSI and emphasize the importance of targeted strategies for improving pediatric patient safety.

The tambaqui Colossoma macropomum is the main species of edible fish originating from fish farming in the Amazon region. This study aimed to determine and compare the hematological and biochemical parameters of tambaqui from fish farms in municipalities in the Metropolitan Region of Manaus, Amazonas, Brazil. Two fish farms were sampled in a semi-excavated pond-type breeding system in each of the five towns investigated (Presidente Figueiredo, Manaus, Iranduba, Manacapuru and Novo Airão), totaling ten breeders. On each farm, ten specimens were captured, totaling 100 animals. Blood was collected by caudal puncture, and hematological and biochemical parameters were determined using the methodology described for teleosts fish. For the erythrogram in the variables of hematocrit, hemoglobin concentration and erythrocytes, significant differences were observed in Iranduba and Novo Airão, demonstrating indications of anemic processes and dehydration. For plasma biochemistry, low levels were observed in fish from Iranduba and Novo Airão. High values in lipid compounds were found in tambaqui from Manacapuru. High intraspecific variation was found in the leukogram and thrombogram, which determined similarities between tambaqui from different farms and municipalities. On the other hand, fish from Manacapuru have an inappropriate diet, indicated by the high levels of cholesterol and triglycerides found in the blood.

In our study, we investigated the prognostic significance of hematological markers—NLR (Neutrophil-to-Lymphocyte Ratio), PLR (Platelet-to-Lymphocyte Ratio), and RDW-CV (Red Blood Cell Distribution Width - Coefficient of Variation)—in 117 glioblastoma patients. Data collected from January 2016 to December 2018 included demographics, clinical scores, and treatment regimens. Unlike previous research, which often examined these markers solely before surgery, our unique approach analyzed them at multiple stages: preoperative, postoperative, and before adjuvant therapies. We correlated these markers with overall survival (OS) and progression-free survival (PFS) using statistical tools, including ANOVA, Cox regression, and Kaplan-Meier survival analyses, employing SPSS version 29.0. Our findings revealed notable variations in NLR, PLR, and RDW-CV across different treatment stages. NLR and PLR decreased after surgery, with some stabilization post-STUPP phase (NLR: p=0.007, η2p=0.06; PLR: p=0.001, η2p=0.23), while RDW-CV increased post-surgery and during subsequent treatments (RDW-CV: p < 0.001, η2p=0.67). Importantly, we observed significant differences between the preoperative phase and other treatment phases. Additionally, higher NLR and RDW-CV at the second-line treatment and disease progression were associated with an increased risk of death (NLR at 2nd line: HR=1.03, p=0.029; RDW-CV at progression: HR=1.14, p=0.004). We proposed specific marker cutoffs that demonstrated significant associations with survival outcomes when applied to Kaplan-Meier survival curves (NLR at 2nd line < 5: p<0.017; RDW-CV at progression < 15: p=0.007). Elevated NLR and RDW-CV at later treatment stages correlated with poorer OS and PFS. No significant preoperative differences were detected. These biomarkers may serve as non-invasive tools for glioblastoma management.

The brown pelican (Pelecanus occidentalis) is a species often affected by natural and man-made disasters such as hurricanes and oil spills as well as general human activities; that subsequently receives medical care and rehabilitation. During rehabilitation, blood may be collected for various testing to help with diagnosis, treatment, and monitoring. Reference intervals for this species are limited, dated, and typically from small sample sizes. Seventy one presumed healthy brown pelicans were sampled as a part of their pre-release examination from rehabilitation at the Wildlife Center of Texas after a large volume stranding in December 2014 to January 2015, and various venous analytes were measured to establish updated reference intervals for Brown Pelicans. Fibrinogen was measured via heat precipitation and the Abaxis VSPro equine Fibrinogen cartridge to determine reference intervals, and in an attempt to validate the VSPro for use in avian species. Abaxis VS2 Avian/Reptile Chemistry panel, iSTAT CG4+, and iSTAT Chem8+ results in addition to body condition score, spun PCV, cloacal temperature and fibrinogen were measured. Proposed reference intervals for brown pelicans are presented. Fibrinogen results were not comparable between the gold standard method and the VSPro, indicating that the VSPro is not appropriate for use in brown pelicans.

Certain micronutrients exhibit immunomodulatory effects. However, no intervention has yet investigated the effect of an individualized supplementation on the severity of upper respiratory tract infections (URI). Therefore, we investigated whether a personalized supplementation moderates the incidence and severity of URI. Selenium, zinc, and vitamin D was measured from 59 healthy participants ) in dried blood spots. Accordingly, a personalized supplement was provided with or without the respective micronutrients. We used WURSS-21 questionnaires to assess the disease status. The blood values converged during the intervention and micronutrients no longer differed at the end of the intervention period between treated and untreated volunteers. The incidence and severity of the illness did not significantly differ between the groups. However, when analyzing the WURSS-21 score by the intention to treat, the initially randomized treatment arm revealed a significantly higher score than the placebo arm. Upon acute administration, individualized combination of selenium, zinc and vitamin D does not reduce the number or contribute to a milder course of URIs. Therefore, supplementation in acute infectious situations seems questionable. Further studies must address the habitual diet in more detail to better understand the impact of individual micronutrient status on the prevention of URI.

Several epidemiological studies and intervention trials have demonstrated that flavanols present in grapes and blueberries can lower the risk of cardiovascular disease. However, the mechanisms of action of these compounds remain unclear due to their low bioavailability. A polyphenol-rich grape and blueberry extract (PEGB) contained about 16% flavanol, of which 11% was monomer and 4% was dimer. A sensory test investigated the oral perception of a PEGB. At concentrations where quercetin had almost no detectable taste, PEGB exhibited significant astringency. Furthermore, in comparing the redox properties against O2･- using a luminescence method, PEGB acted as a prooxidant at low concentrations, promoting O2･-production and scavenging O2･-at high concentrations under pH conditions similar to oral cavity and intestine. In contrast, quercetin showed antioxidant activity at any concentration. A single oral administration of PEGB to rats showed a significant increase in skeletal muscle arteriolar blood flow. According to these results, PEGB containing flavanols displays a potent astringent flavor, increases O2･-production at low concentrations in a neutral pH environment as well as oral and intestine, and considerably enhances blood flow to skeletal muscles after a single dose in rats. The results of this study indicate a need to investigate the causal relationship between oral perception, redox properties, and bioactivity of polyphenols.

Fundus image registration plays a crucial role in the clinical evaluation of ocular diseases, such as diabetic retinopathy and macular degeneration, necessitating meticulous monitoring. The alignment of multiple fundus images enables the longitudinal analysis of patient progression, widening the visual scope, or augmenting resolution for detailed examinations. Currently, prevalent methodologies rely on feature-based approaches for fundus registration. However, certain methods exhibit high feature point density, posing challenges in matching due to point similarity. This study introduces a novel fundus image registration technique integrating U-Net for the extraction of feature points employing FIVES for its training and evaluation, a novel and large dataset for blood vessels segmentation, prioritizing point distribution over abundance. Subsequently, the method employs medial axis transform and pattern detection to obtain feature points characterized by the Fast Retina Keypoint (FREAK) descriptor, facilitating matching for transformation matrix computation. Assessment of the vessel segmentation achieves 0.7559 for Intersection Over Union (IoU), while evaluation on the Fundus Image Registration Dataset (FIRE) demonstrates the method’s comparative performance against existing methods, yielding a registration error of 0.596 for area under the curve, refining similar earlier methods and suggesting promising performance comparable to prior methodologies.

Diabetes mellitus – type 2 (DM2) is a hypercoaguable state with enhanced platelets (PLTs) activation and increased clotting factor production. Simultaneously, the fibrinolytic cell system is inhibited due to formation of clots with high resistance to fibrinolysis. The stages of PLTs "activation" have been well-characterized microscopically, morphometrically and nanomechanically (by light microscope, transmisiion electron microscope - TEM, scanning electron microscope - SEM and atomic force microscope - AFM). Thrombocytes in "acivated" (pro-coagulant) state play central role in two main biological processes: hemostasis and repair of vascular vessels. Pro-coagulant PLTs participate in generation of thrombin and in development of fibrin fibers in the clot matrix. Enhanced PLTs reactivity in dibetic- (diabetes mellitus - DM2) patients is considered as a "pro-thrombotic" state. In the retrospective- and prospective- studies on the topic, the higher are the PLTs' hematometrical indices: PLTs (count), MPV (mean platelet volume), PDW (platelet distribution width), PCR (plateletcrit), as well as PLTs/Ly ratio. The PLТs parameters/indices are usefull biomarkers in early diagnosis and prognosis of DM2. The precise studies of PLTs' state of activation during DM2 might be useful for creation of new diabetes (DM2) treatment strategies and effective medicines. Using the amount of blood glucose, attached to hemoglobin (HbA1c values) as markers of glycemic control in diabetic patients, researchers have observed association between MPV and medications as Insulin, Metformin, sulphonyl ureas. Computational modellng of PLTs' activation in DM2 is also a controlling factor for thrombocyte distribution and margination in bood vessels, associated with micro- and macrovascular disease in DM2. PLTs-derived miRNAs are novel molecular biomarkers for diagnosis and prognosis of DM2, insulin resistance and diabetes complications. We have proposed (2010) oleic acid (OA) as a substance suppressing "PLT hyperactivation" and inhibiting “thrombocyte aggregation”. Antiplatelet agents, natural plant products including, could be effective in the prevention and the secondary treatment of micro- and macrovascular complications in the type 2 Diabetes mellitus. Our proposal on following up of a combination of hematological-, hemorheological- and hemostatic parameters (indices) as a new way in diagnosis, treatment, predicting and management of DM2 and its related vascular complications, probably could be more explored in future studies.

Background: Orthostatic hypotension (OH) is associated with higher risk of mortality in general population however not studied in cancer population. The study aimed to assess the prevalence of OH in cancer patients compared to the non-cancer population. Methods: A total of 411 patients (mean age 63.5 ± 10.6 years) were recruited: patients with active cancer (n = 223) and patients hospitalized for other reasons but without cancer diagnosis (n = 188). Medical history was collected and an orthostatic challenge test was performed. OH was defined as blood pressure (BP) decrease on standing ≥ 20 mmHg for systolic or ≥ 10 mmHg for diastolic BP in 1 or 3 minutes; or systolic BP decrease < 90 mmHg. Results: The prevalence of OH in cancer was significantly higher than in subjects without cancer- 28.7% vs. 16.5%, respectively, P = 0.003). OH was the most common in lung cancer, 57.5%. In single variable analysis, the predictors of OH were: cancer presence, age ≥ 65 years, and body mass index (BMI) ≥ 30 kg/m2. In the multivariable model, the strongest independent predictor of OH was cancer status doubling the risk of OH; BMI ≥ 30 kg/m2 and diabetes. Conclusions: Cancer patients are characterized by a high prevalence of OH. In this population, the recommendation of routine orthostatic challenge tests should be considered.

Background: Several kinds of research say that adjuvant blood glucose and blood pressure are usual, but an efficient solution for medical application count remains. This review analyzes the pandemic blood pressure and blood glucose to identify the publications which tell about the clinical practices and research gaps in systematic research.Methods: A study guides to identify the research of Blood Pressure (BP) and Blood Glucose. In order to analyze the recent innovations and research on BP and Blood glucose, the relevant publications and literature from journals were identified.Results: Co-morbidity of BP and Blood glucose is reported as very high. The commonness of blood pressure is thrice as high in type I diabetes patients and almost two times higher in type II diabetes patients when compared to others without Diabetes. The pervasiveness of getting depression is more in the female when compared with men. A detailed study about the linkage of BP and blood glucose tells that the relationship between them is not exactly clear.Limitations: Nearly all reviews providing the linkage of BP and blood glucose are with some limitations and they are not providing any clear conclusion.Conclusions: Present research tells that people having high blood glucose will have a greater chance of getting high blood pressure. More research is needed to state the linkage between BP, blood glucose, and the growth of diabetes mellitus issues and to provide support for managing Diabetes.

Glioblastoma (GBM) is the most aggressive brain cancer. To model GBM in research, orthotopic brain tumor models, including syngeneic models like GL261 and genetically engineered mouse models like TRP, are used. In longitudinal studies, tumor growth and treatment response are typ-ically tracked with in vivo imaging, including bioluminescence imaging (BLI), which is quick, cost-effective, and easily quantifiable. However, BLI requires luciferase-tagged cells, and recent studies indicate that the luciferase gene can elicit an immune response, leading to tumor rejection and experimental variation. We sought to optimize the engraftment of two luciferase-expressing GBM models, GL261 Red-FLuc and TRP-mCherry-FLuc, showing differences in tumor take, with GL261 Red-FLuc cells requiring immunocompromised mice for 100% engraftment. Immuno-histochemistry and MRI revealed distinct tumor characteristics: GL261 Red-FLuc tumors were well-demarcated with densely packed cells, high mitotic activity, and vascularization. In con-trast, TRP-mCherry-FLuc tumors were large, invasive, and necrotic, with perivascular invasion. Quantifying tumor volume using the HALO® AI analysis platform yielded results comparable to manual measurements, providing a standardized and efficient approach for reliable high-throughput analysis of luciferase-expressing tumors. Our study highlights the importance of considering tumor engraftment when using luciferase-expressing GBM models, providing in-sights for preclinical research design.

The blood count is crucial for assessing bone marrow's cell production and differentiation during infections, gauging disease severity, and monitoring therapeutic responses. The profile of blood count in chronic form of paracoccidioidomycosis (PCM) has been insufficiently explored. To better understand the changes in hematological cells in different stages of the PCM chronic form, we evaluated the blood count, including immature blood cells in automated equipment, before and during the treatment follow-up of 62 chronic PCM patients. Predominantly male (96.8%) with an average age of 54.3 (SD 6.9) years, participants exhibited pre-treatment conditions such as anemia (45.2%), monocytosis (38.7%), and leukocytosis (17.7%) which became less frequent after clinical cure. Anemia was more prevalent in severe cases. Notably, hemoglobin and reticulocyte hemoglobin content increased, while leukocytes, monocytes, neutrophils, immature granulocytes, and platelets decreased. Chronic PCM induced manageable hematological abnormalities, mainly in the red blood series. Monocytosis, indicating monocytes' role in PCM's immune response, was frequent. Post-treatment, especially after achieving clinical cure, significant improvements were observed in various hematological indices, including immature granulocytes and reticulocyte hemoglobin content, underscoring the impact of infection on these parameters.

This study was conducted to determine the role of pre-operative 2 weeks use of Finasteride in reducing intra-operative blood loss in patients undergoing monopolar TURP. Number of enrolled patients were 120, on the basis of inclusion criteria. Patients who were candidates of monopolar TURP were given 5mg Finasteride for 2 weeks before the surgery. On the 13th day of medicine, they got admitted in ward and prepared for surgery. During surgery intra-operative irrigation fluid was measured and gathered, then tested for Hemoglobin and the blood loss was calculated with equation formula. Blood loss evaluation was done on the basis of irrigation fluid, hemoglobin in irrigation fluid, preoperative hemoglobin and resected tissue weight. Significant reduction in blood loss was observed in interventional group as compared to the control group. Mean blood loss was 296ml in Group-A and 370ml in Group-B while blood loss per gram was 11.7ml/g in Group-A and 14.7 ml/g in Group-B. Mean operative time was measured 42 minutes in Group-A and 49 minutes in Group-B. This research proclaims a clear-cut supremacy of pre-operative use of Finasteride for two weeks. It significantly reduces intraoperative blood loss and blood loss per gram in patients undergoing monopolar TURP.

The coronavirus pandemic was declared by the World Health Organization (WHO) in 2020, and a global genetic vaccination program has been rapidly implemented as a fundamental solution. However, many countries around the world have reported that so-called genetic vaccines, such as those using modified mRNA encoding the spike protein and lipid nanoparticles as the drug delivery system, have resulted in post-vaccination thrombosis and subsequent cardiovascular damage, as well as a wide variety of diseases involving all organs and systems, including the nervous system. In this article, based on these circumstances and the volume of evidence that has recently come to light, we call the attention of medical professionals to the various risks associated with blood transfusions using blood products derived from people who have suffered from long COVID and from genetic vaccine recipients, including those who have received mRNA vaccines, and we make proposals regarding specific tests, testing methods, and regulations to deal with these risks. We expect that this proposal will serve as a basis for discussion on how to address post-vaccination syndrome and its consequences following these genetic vaccination programs.

The well-being and sociability of individuals have always been part of modernity. The development of new technologies that meet these aspirations is receiving increasing attention. Thus, strengthening the desired objectives of these tools and minimizing their undesirable side effects is the subject of a growing commitment. The present contribution aims, in this context, to evaluate and analyze the desired and undesirable effects of the interaction of electromagnetic fields with living tissues in general. This involves routines reinforcing expected functions as well as those controlling and protecting against undesirable effects. First, the interactions of electromagnetic fields with tissues are analyzed, involving their thermal biological effects of desired and undesired exposures. The roles of blood and sap fluids in bio-affected tissues are then analyzed. Secondly, the governing electromagnetic, bio-heat equations, and their coupled solution are studied. Third, the thermal behavior of tissues and the exposure adverse effects are examined. Next, monitoring and defending of the effects of exposures are discussed. This contribution illustrates and discusses mathematical modeling routines based on a generalized interaction of electromagnetic fields with living tissues.

Introduction: Postpartum hypertension (PPHT) is hypertension that persists or develops directly after pregnancy. PPHT affects 10% of pregnancies and is the most common cause for re-hospitalization after giving birth. In general, PPHT stems from hypertensive disorders of pregnancy (HDP). The aim of the current interim report of the Basel PPHT registry is to describe the cohort, and to determine feasibility and acceptance of a home-based telemonitoring management strategy (HBTMS) in women with PPHT. Methods: Enrollment in the cohort began in June 2020 during the SARS-CoV-2 pandemic at the University Hospital Basel. Women in the maternity ward were screened for preexisting hypertension, HDP, and de novo postpartum hypertension and after consenting, were enrolled. In this pragmatic non-randomized prospective trial, women in the PPHT cohort could choose, between a HBTMS or usual care which consisted of in-hospital appointments at the hypertension clinic. HBTMS was defined as a smartphone application or a programmed spreadsheet to report blood pressure followed by telephone consultations. Standard of care was hospital-based visits as clinically needed after discharge. All participants were assessed three months after delivery with a standardized clinical visit including a 24-hour blood pressure measurement, blood, biomarker, and urine analysis. Results: 311 participants were enrolled from 06/20-08/23. Mean age was 34±5.3 years. Regarding pregnancy-related medical history: 10 % had preexisting hypertension, 27.3 % gestational hypertension, 53% preeclampsia (PE), 0.3% eclampsia, 6% HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) and 18.3% had de novo PPHT. More than one diagnosis was possible. Family history of cardiovascular disease was seen in 49.5%, 7.5% had a family history of PE. 23.3% were determined as high risk for PE during pregnancy. The most common type of delivery was C-Section (68.5%), mean hospital stay was 6.3 days (±3.9) and IUGR (intrauterine growth restriction) was seen in 21% of the newborns. 99% of participants chose a home-based management strategy. Conclusion: This first description of the Basel PPHT Cohort showed that a HBTMS is well accepted. This is particularly relevant in the direct postpartum period and even more pertinent when the exposure of hospital visits should be avoided when possible.

Xanthone derivatives, a class of natural compounds abundantly found in plants such as mangosteen (Garcinia mangostana) and certain herbs, have garnered substantial interest due to their diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer activities. Recent investigations have unveiled their potential as modulators of enzymatic activity, prompting exploration into their effects on hyaluronidase-mediated HA degradation, and their effects in topical treatment of telangiectasia and rosacea. Telangiectasia and rosacea are common dermatological conditions characterized by chronic skin inflammation, vascular abnormalities, and visible blood vessels, resulting in significant cosmetic concerns and impaired quality of life for affected individuals. This review aims to provide a comprehensive overview of the current understanding regarding the interplay between mechanisms of action by which xanthone derivatives exert their therapeutic effects, including the inhibition of pro-inflammatory cytokines, modulation of oxidative stress pathways, and regulation of vascular endothelial growth factors. Furthermore, we will discuss the implications of harnessing xanthone derivatives as therapeutic agents for mitigating vascular dysfunction and its associated pathologies, thereby offering insights into future research directions and therapeutic strategies in the field of vascular biology.

Alzheimer's disease (AD) remains a significant challenge in the field of neurodegenerative disor-ders, even nearly a century after its discovery, due to the elusive nature of its causes. The develop-ment of drugs that target multiple aspects of the disease has emerged as a promising strategy to address the complexities of AD and related conditions. The immune system's role, particularly in AD, has gained considerable interest, with nanobodies representing a new frontier in biomedical research. Advances in targeting antibodies against amyloid-β (Aβ) and using messenger RNA for genetic translation have revolutionized the production of antibodies and drug development, open-ing new possibilities for treatment. Despite these advancements, conventional treatments for AD, such as Cognex, Exelon, Razadyne, and Aricept, often have limited long-term effectiveness, under-scoring the need for innovative solutions. This necessity has led to the incorporating of advanced technologies like artificial intelligence and machine learning into the drug discovery process for neurodegenerative diseases. These technologies help identify therapeutic targets and optimize lead compounds, offering a more effective approach to addressing the challenges of AD and similar conditions.

Coccomyxa subellipsoidea KJ (C-KJ) is a green alga with unique immunoregulatory characteristics. Here, we investigated the mechanism underlying the modification of T cell function by C-KJ components. The water-soluble extract of C-KJ was fractionated into protein (P) and sugar (S) fractions [acidic (AS), basic (BS), and neutral (NS)]. These fractions were used for the treatment of peripheral blood mononuclear cells stimulated with toxic shock syndrome toxin-1. Transcriptome analysis revealed that both P and AS enhanced the expression of the genes encoding metallothionein (MT) family proteins, inflammatory factors, and T helper (Th) 17 cytokine and suppressed that of those encoding Th2 cytokines in stimulated T cells. The kinetics of MT1 and MT2A gene expression showed a transient increase in MT1 and maintenance of MT2A mRNA after T cell stimulation in the presence of AS. The kinetics of Th17-related cytokine secretion in the early period were comparable to those of MT2A mRNA. Furthermore, our findings revealed that static, a STAT-3 inhibitor, significantly suppressed MT2A gene expression. These findings suggest that the expression of MTs is involved in the immune regulatory function of C-KJ components, which is partially regulated by Th17 responses, and may help develop innovative immunoregulatory drugs or functional foods.

Hemodynamics is the eternal theme of the circulatory system. Abnormal hemodynamics and cardiac and pulmonary development intertwine to form the most important features of children with congenital heart diseases (CHDs), thus determining these children’s long-term quality of life. However, due to the lack of neonatal rodent models of CHDs, it is unclear how CHD-associated hemodynamics shape postnatal cardiac and pulmonary development. Here, we review the varieties of hemodynamic abnormalities that exist in children with CHDs, the recently developed neonatal rodent models of CHDs, and the inspirations these models have brought us in the areas of cardiomyocyte proliferation and maturation, and in alveolar development. Furthermore, current limitations, future directions, and clinical decision-making based on these inspirations are highlighted. Understanding how CHD-associated hemodynamic scenarios shape postnatal heart and lung development may provide a novel path to improving the long-term quality of life of children with CHDs, transplantation of stem cell–derived cardiomyocytes, and cardiac regeneration.

SARS-CoV-2 is the Coronavirus responsible for the COVID-19 pandemic. Even though we are no more in a pandemic situation, people are getting infected some of them needing hospitalization, and a few of them die. Methods: We did a retrospective study including 445 patients who accessed the Emergency Section of Policlinico Umberto I, Rome, Italy, where they had routine blood exams. In this study, we concentrated on the complete blood count, creatinine, and azotemia. The data was analyzed using ANOVA, Spearman correlation, and ROC analysis. They were divided into four groups based on their outcome: (1) the emergency group (patients with mild forms who were quickly discharged); (2) the hospital ward group (patients who after admission to the emergency section were hospitalized in a COVID-19 ward); (3) the intensive care unit (ICU) group (patients that after the admission in the emergency section required intensive assistance); (4) the deceased group (patients that after the admission in the emergency section had a fatal outcome). Results: We found significant changes for creatinine, azotemia, hematocrit, mean corpuscular hemoglobin concentration, basophils, monocytes, red blood cell distribution width, hemoglobin, hematocrit, and red blood cell numbers by ANOVA according to their outcomes, particularly for the deceased group. Also, we found outcome correlations for eosinophils, hemoglobin, hematocrit, mean corpuscular hemoglobin concentration, lymphocyte, neutrophil, platelet, and red blood cell number and red blood cell distribution width. Conclusions: This study discloses an association between “classical” routine blood biomarkers and the severity of outcomes in Omicron patients.

Exposure to vaccine lipid nanoparticles, mRNA, adenoviral DNA, and or Spike protein from one of the approved Covid-19 vaccines, or through secondary exposure, as through blood transfusion, is a potential source of harm. Blood reactions are an acknowledged side-effect of Covid-19 vaccination, not limited to hemolysis, paroxysmal nocturnal hemoglobinuria, chronic cold agglutinin disease, immune thrombocytopenia, haemophagocytosis, hemophagocytic lymphohistiocytosis, and many other blood related conditions. The observation of adverse events has motivated investigation into the cardiovascular mechanisms of harm by Covid-19 vaccines, and the biodistribution of vaccine contents. Biodistribution may not be limited to the body of the vaccine recipient, as a growing body of evidence demonstrates the possibility of secondary exposure to vaccine particles. These can be via bodily fluids and include the following routes of exposure: blood transfusion, organ transplantation, breastfeeding, and possibly other means. As covid-19 vaccines are associated with an increased risk of stroke, the persistence of vaccine artifacts in the blood presents a possible threat to a recipient of a blood donation from a vaccinated donor who suffered from vaccine induced thrombosis or thrombocytopenia. (VITT) We assess the feasibility and significance of these risks through an overview of the case report literature of blood disorders in vaccinated individuals, pharmacovigilance reports from the US Vaccine Adverse Events Reporting System (VAERS) and a meta-analysis of the available literature on organ transplants from vaccinated organ donors. Our analysis establishes biological mechanistic plausibility, a coherent safety signal in pharmacovigilance databases for secondary vaccine contents exposure (for the cases of blood transfusion and breastfeeding) and also an elevated level of adverse events in organ transplants from VITT-deceased donors, echoing increases in organ transplantation related complications seen in national statistics for some countries. Secondary exposure to vaccine artifacts is a potential explanation for some of the cases put forth, and requires a deeper investigation.

The central nervous system (CNS) is the final frontier in drug delivery because of the blood-brain barrier (BBB), which poses significant barriers to the access of most drugs to their targets. Kynurenic acid (KYNA), a tryptophan (Trp) metabolite, plays an important role in behavioral functions and abnormal KYNA levels have been observed in neuropsychiatric conditions. The current challenge lies in delivering KYNA to the CNS owing to its polar side chain. Recently, C-3 side chain modified KYNA analogs have been shown to cross the BBB; however, it is unclear whether they retain the biological functions of the parent molecule. This study examined the impact of KYNA analogs, specifically SZR-72, SZR-104, and the newly developed SZRG-21, on behavior. The analogs were administered intracerebroventricularly (i.c.v.), and their effects on the motor domain were compared with those of KYNA. Specifically, open field (OF) and rotarod (RR) tests were employed to assess motor activity and skills. SZR-104 increased horizontal exploratory activity in the OF test at a dose of 0.04 μmol/4 μL, while SZR-72 decreased vertical activity at doses of 0.04 and 0.1 μmol/4 μL. In the RR test, however, neither KYNA nor its analogs showed any significant differences in motor skills at either dose. Side chain modification affects affective motor performance and exploratory behavior, as the results show for the first time. In this study, we showed that KYNA analogs alter emotional components such as motor-associated curiosity and emotions. Consequently, drug design necessitates the development of precise strategies to traverse the BBB while paying close attention to modifications in their effects on behavior.

This cross-sectional study evaluated the validity of three alternative methods compared to the gold standard 24-h urine collection for estimating dietary sodium intake, a modifiable risk factor for hypertension, among middle-aged and older adults with elevated blood pressure. These included spot urine collection (using Kawasaki, Tanaka, and INTERSALT equations), 24-h dietary recall, and food frequency questionnaire responses, compared against 24-h urine collection in a subset of 65 participants (aged 50–75 years, 58.5 % women, 61.6 % hypertensive) from the DePEC-Nutrition trial. The validity of the methods was assessed using bias, Spearman correlation coefficient (SCC), intraclass correlation coefficient (ICC), and Bland-Altman analysis. Among the alternative methods, spot urine collection using the Kawasaki equation showed the strongest correlation (SCC 0.238; ICC 0.119, 95 % CI -0.079 to 0.323) but it exhibited a significant bias (1414 mg/day, p-value < 0.001) relative to 24-h urine collection. Conversely, dietary surveys had a smaller bias but wider limits of agreement. These findings underscore the complexities of accurately estimating dietary sodium intake using spot urine collection or dietary surveys in this specific population, suggesting that a combination or refinement of existing methodologies might improve accuracy. Further research with larger samples is necessary to develop more reliable methods for assessing sodium intake in this high-risk group.

Combined radiation with hemorrhage (combined injury, CI), exacerbates hematopoietic acute radiation syndrome and mortality compared to radiation alone (RI). We evaluated the effects of RI or CI on blood cell depletion as a biomarker to differentiate the two. Male CD2F1 mice were exposed to 8.75 Gy γ- radiation (60Co). Within 2 h of RI, animals were bled under anesthesia 0% (RI) or 20% (CI) of total blood volume. Blood samples were collected at 4-5 h and days 1, 2, 3, 7, and 15 after RI. CI decreased WBC at 4-5 h and continued to decrease them until day 3; counts then stayed at the nadir up to day 15. CI decreased neutrophils, lymphocytes, monocytes, eosinophils and basophils more than RI on day 1 or day 2. CI decreased RBCs, hemoglobin and hematocrit on days 7 and 15 compared to RI, whereas Hemorrhage alone returned to the baseline on days 7 and 15. RBCs depleted after CI faster than post RI. Hemorrhage alone increased platelet counts on days 2, 3, and 7, which returned to the baseline on day 15. Our data suggest that WBC depletion may be a biomarker within 2 days post-CI and RBC depletion after 3 days post-CI.

Applying the iterative methodology for dimensionality reduction/feature selection using categorical gradient boosted trees, as it has been defined in and has been successfully applied on similar datasets in and , on a dataset consisted of 12708 gene expressions coming from 5052 individuals from 105 studies, we classify whether a person has acute myeloid leukaemia (AML) or is healthy. A CatBoost model on a dataset with reduced dimensions of 72 genes reached a ROC-AUC score of 0.9973 using ten fold cross validation (10CV) and ROC-AUC: 0.9988 on an inference dataset. We further investigate the options of using less genes that potentially could be used in clinical practise and genes than have not been associated to AML yet, or to blood cancer in general. On the same folds of the 10CV and on the same inference dataset the performance of the tuned CatBoost models show that it could be the case that not all genes with an association to AML have been found yet and 19 genes could be enough to predict AML: CatBoost63 (ROC-AUC: 0.9941, Test: 0.9942), CatBoost19: (ROC-AUC: 0.9946, Test: 0.9941) and CatBoost15: (ROC-AUC: 0.9922, Test: 0.9900). In addition, our results verify that a gene diagnostic test for AML could be possible in the future as well as further research is needed on these 15 genes that it could lead to new and better drugs.

The ability of recombinant, SARS-CoV-2 Spike (S) protein to modulate the production of two COVID-19 relevant, pro-inflammatory cytokines (IL-6 and IFN-γ) in PBMC cultures of healthy, pre-Covid-19 subjects was investigated. We observed that cytokine production was largely and diversely modulated by the S protein depending on antigen or mitogen stimulation, as well as on the protein source, insect (S-in) or human (S-hu) cells. While both proteins co-stimulated cytokine production by polyclonally CD3-activated T cells, PBMC activation by the mitogenic lectin Concanavalin A (Con A) was up modulated by S-hu protein and down-modulated by S-in protein. These modulatory effects were likely mediated by the S glycans as demonstrated by direct Con A-S binding experiments and use of yeast mannan as Con A binder. While being ineffective in modulating memory antigenic T cell responses, the S proteins and mannan were able to induce IL-6 production in unstimulated PBMC cultures and upregulate the expression of Mannose Receptor (CD206), a marker of anti-inflammatory M2 macrophage. Our data point to a relevant role of N-glycans, particularly N-mannosidic chains, decorating the S protein in the immunomodulatory effects here reported. These novel biological activities of the S glycan ectodomain may add to the comprehension of Covid-19 pathology and immunity to SARS-CoV-2.

Leukemia, contributing to 3% of all cancer cases in the United States, presents a significant challenge in treatment due to its diverse subtypes, each dis-playing unique genetic and molecular abnormalities. The aggressive growth of ab-normal blood cells compromises immune function and poses challenges in developing effective therapeutic approaches. Unlike solid tumors, surgical resection is not an option, limiting treatment strategies to chemotherapy, immunotherapy, and radiation therapy, which may be nonspecific and lead to organ damage and toxicity. Anthracyclines, widely used in hematological tumors, face limitations due to severe cardiotoxicity, causing progressive cardiomyopathy and, in severe cases, congestive heart failure. Heart failure incidence is significantly higher in cancer patients treated with anthracyclines over 5, 10, and 15 years. Early detection of left ventricular dysfunction and cardiotoxicity is crucial to mitigate progression to congestive heart failure (CHF) in this population. Recent research by Bayrón-Marrero et al. reveals that lower levels of plasma soluble TREM-Like Transcript-1 (s-TLT-1), a platelet-specific receptor, correlate with left ven-tricular dysfunction in cardiovascular disease patients. Those with s-TLT-1 levels ex-ceeding 544 pg/mL exhibit a significant association with congestive heart failure. These findings suggest the potential use of s-TLT-1 as a diagnostic screening tool for early detection and treatment of anthracycline-induced CHF in leukemia patients.

The expression of non-coding RNAs varies greatly depending on the cell type and physiological state. Changes in expression affect the regulatory properties of these molecules. We investigated RNA-seq data from sorted blood cells of healthy control donors and severe COVID-19 patients. Our aim was to display a distinguishable piRNA differential expression portrait for each type of cell and to study the behavior of piRNA in the blood cells of COVID-19 patients. Overall piRNA expression in sorted control cells (erythrocytes, monocytes, lymphocytes, eosinophils, basophils, neutrophils) differs depending on cell type. Four of the most abundant piRNA were expressed relatively equally in all cell types, they included piR-49145, piR-49144, piR-49143 and piR-33151. By reviewing piRNA expression in each group of sorted cells from severe COVID-19 patients we observed 3 upregulated and 10 downregulated piRNAs in erythrocytes. Monocytes were presented with a larger amount of statistically significant piRNA, 4 upregulated and 35 downregulated. In lymphocytes, all 19 piRNAs were upregulated.

Adenosine is a multifunctional nucleoside with several roles across various levels in organisms. Beyond its intracellular involvement in cellular metabolism, extracellular adenosine potently influences both physiological and pathological processes. In relation to its blood level, adenosine impacts the cardiovascular system, such as heart beating rate and vasodilation. To exploit the adenosine levels in the blood, we employed the liquid chromatography method coupled with mass spectrometry (LC-MS). Immediately after the collection, a blood sample mixed with acetonitrile solution that is either enriched with 13C-labeled adenosine or a newly generated mixture is transferred into the tubes containing the defined amount of 13C-labeled adenosine. The 13C-enriched isotopic adenosine is used as an internal standard, allowing for more accurate quantification of adenosine. This novel protocol for LC-MS-based estimation of adenosine delivers a rapid, highly sensitive, and reproducible means for quantitative estimation of total adenosine in blood. The method also allows quantification of a few catabolites of adenosine, i.e., inosine, hypoxanthine, and xanthine. This advancement provides the analytical tool that has the potential to enhance our understanding of adenosine's systemic impact and pave the way for further investigations into its intricate regulatory mechanisms.

Incretin effect helps in regulating glucose homeostasis and maintaining glycaemic control within the human body. This effect is achieved by the two naturally occurring incretin hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Such hormones released by specialized entero-endocrine cells of the gastrointestinal tract cause insulin augmentation after food consumption. However, incretin effects are impaired in type 2 diabetic, primarily attributed to the deterioration of GLP-1 function along with decreased GLP-1 receptor expression. Targeting this hormone has, therefore, become an important therapeutic approach to treat this diabetic condition. Native GLP-1’s brief half-life and rapid proteolytic degradation have generated significant enthusiasm in uncovering the long-acting GLP-1 receptor (GLP-1R) agonists to manage type 2 diabetes. These synthetic peptides mimic the natural GLP-1 to activate GLP-1R and effectively exert various physiological benefits in terms of weight management, blood pressure, lipid profile, obesity and major adverse cardiovascular event. This review paper provides insights into the structure, function and expression of GLP-1 and its receptor. It also summarizes existing literature regarding different types of GLP-1 receptor agonists, their effects on blood pressure and how they exert their actions. While animal models have contributed significantly to this area of study, the scarcity of human studies is noted, indicating a need for more investigation in this domain. Expanding research in humans will help in comprehending the impact of GLP-1 receptor agonists on blood pressure regulation and their underlying mechanisms.

Electrospun fiber scaffolds are widely used in small diameter vascular tissue engineering because they mimick organizational structure and biological function of natural extracellular matrix. However, there is still one problem of low patency rate in the long term. The main reasons are the mismatch of compliance and the easy formation of thrombus. Therefore, it is very important to promote the rapid endothelialization of small diameter tissue engineering blood vessels by regulating the topological structure and biological properties of electrospun fiber scaffolds. Firstly, crimped polylactic acid (PLA) fibers were prepared by heat treatment to mimick the crimped structure and nonlinear mechanical properties of the elastic membrane of blood vessel wall. It improved effectively the aspect ratio of human umbilical vein endothelial cells (HUVECs) and promoted lateral alignment and growth. Then, crimped PLA fibers with three levels of pore structure were prepared by thermal induced phase separation, vapor induced phase separation and laser ablation to enhance the degree of HUVECs infiltrarion and realize patterned cell growth. Crimped PLA fibers with three levels of pore structure promote rapid endothelialization of blood vessels, which is of great significance to achieve long term patency rate of small diameter tissue engineering blood vessels.

Stem cells can be used to treat diabetic mellitus and complications. ω3-docosahexaenoic acid (DHA) derived lipid mediators are inflammation-resolving and protective. This study found novel DHA-derived 7S,14R-dihydroxy-4Z,8E,10Z,12E,16Z,19Z-docosahexaenoic acid (7S,14R-diHDHA), a maresin-1 stereoisomer biosynthesized by leukocytes and related enzymes. Moreover, 7S,14R-diHDHA can enhance mesenchymal stem cell (MSC) functions in the amelioration of diabetic mellitus and retinal pericyte loss in diabetic db/db mice. MSCs treated with 7S,14R-diHDHA were delivered into db/db mice i.v. every 5 days for 35 days. Blood glucose levels in diabetic mice were lowered by 7S,14R-diHDHA-treated MSCs compared to control and untreated MSC groups, accompanied by improved glucose tolerance and higher blood insulin levels. 7S,14R-diHDHA-treated MSCs increased insulin+ β-cell ratio and decreased glucogan+ α-cell ratio in islets, as well as reduced macrophages in pancreas. 7S,14R-diHDHA induced MSC functions in promoting MIN6 β-cell viability and insulin secretion. 7S,14R-diHDHA induced MSC paracrine functions by increasing the generation of hepatocyte growth factor and vascular endothelial growth factor. Furthermore, 7S,14R-diHDHA enhanced MSC functions to ameliorate diabetes-caused pericyte loss in diabetic retinopathy by increasing their density in retina in db/db mice. Our findings provide a novel strategy for improving therapy for diabetes and diabetic retinopathy using 7S,14R-diHDHA-primed MSCs.

A crucial aspect in developing machine learning algorithms (or any type of predictive models) is the comparison of different algorithmic candidates based on evaluation criteria that measure their accuracy and practical value in terms of successfully capturing the complexity of the underlying problem and generalizing in a wide range of real-world scenarios. In the domain of diabetes mellitus machine learning techniques are widely employed in the prediction of future values of glucose concentration in the blood in order to assist the patient in avoiding deviations from the normo-glycemic value range and the consequences of hyper- and hypoglycemia. In the relative literature there is an apparent lack of a uniformly adopted evaluation metric which could combine the clarity and direct comparative nature of statistical mathematical formulas dealing with prediction error residuals (e.g., the RMSE) with the clinical insights and the visual-qualitative approach of clinical evaluation tools (e.g., Clarke's EGA). Mean Adjusted Exponent (MADEX) error metric, proposed in this paper, attempts to address this need by providing a validation tool based on an easy to implement mathematical formula, that incorporates adjustable parameters of clinical significance.

This review article focuses on the upstream pertinent pathophysiology leading to neurodegenerative disease. Specifically, the nexus appears to be blood brain barrier (BBB) leakiness resulting in a two-prong inflammatory disease spectrum damaging the microvasculature and corrupted protein synthesis and degradation with accumulating misfolded toxic proteins. The suboptimal results of removing misfolded proteins means a new approach to disease in the preclinical state is required aimed at other targets.Validated noninvasive imaging and serologic biomarkers of early preclinical disease implemented in the high-risk patient cohort along with periodic surveillance once effective treatments are developed will be required.This review discusses the physiology and pathophysiology of the BBB, new MRI imaging techniques identifying the leak and altered fluid dynamic effects in the preclinical state. The risk factors for disease development, preventative measures, and potential treatment targets are also discussed.

Hypertension is one of the most common primary cardiometabolic diseases and is a major contributor to cardiac mortality and morbidity. Furthermore, cardiac risk factors such as obesity and sedentary lifestyle are often seen in hypertensive patients. Regular exercise acts against these risk factors and improves the overall health of an individual. High-intensity interval training appears to do so in a more efficient way. We used a systematic literature review (SLR) approach to provide an overview of the present literature highlighting the cardiovascular advantages of HIIT in hypertensive individuals. We reviewed 4004 articles from reputable journals published between 2013 and August 14, 2023, focusing on 7 selected papers for in-depth analysis. This systematic review revealed the protective effects of HIIT against cardiac complications in hypertension. All the reviewed articles showed a decrease in blood pressure and many other risk variables of cardiovascular diseases. However, guidelines for this exercise are needed for maximum benefits. Therefore, further research on HIIT is necessary to fully harness its potential.

In CNS drug discovery, estimation of brain exposure of lead compounds is critical for their optimization. Compounds need to cross the blood-brain barrier (BBB) to reach the pharmacological targets in the CNS. The BBB is a complex system involving passive and active mechanisms of transport and efflux transporters such as P-glycoproteins (P-gp) and breast cancer resistance protein (BCRP), which play an essential role in CNS penetration of small molecules. Several in vivo, in vitro and in silico methods are available to estimate human brain penetration. Preclinical species are used as in vivo models to understand the unbound brain exposure by deriving the Kp,uu parameter, the brain/plasma ratio of exposure corrected with the plasma and brain free fraction. MDCK-mdr1 (Madin Darby canine kidney cells transfected with the MDR1 gene encoding for the human P-gp) assay is the most commonly used in vitro assay to estimate compound permeability and human efflux. The in silico methods to predict brain exposure, such as CNS MPO, CNS BBB scores and various Machine Learning models, help save costs and speed up compound discovery and optimization at all stages. These methods enable the screening of virtual compounds and building of a CNS penetrable compounds library as well as optimization of lead molecules for CNS penetration. Therefore, it is crucial to understand these methods' reliability and ability to predict CNS penetration. We review the in silico, in vitro and in vivo data and their correlation with each other and assess published in silico approaches to predict the BBB penetrability of compounds.

Temporal lobe epilepsy (TLE) is associated with reorganization of hippocampal neuronal net-works, gliosis, neuroinflammation, loss of integrity of the blood-brain barrier (BBB) in humans and animal models. More than 30% of epilepsies remain intractable and characterization of the molecular mechanisms involved in BBB dysfunction is essential to the identification of new thera-peutic strategies. In this work, we induced status epilepticus in rats by injection of the proconvul-sant drug pilocarpine that leads to TLE. Using RT-qPCR, double immunohistochemistry and con-focal imaging, we studied at different time points of epileptogenesis (latent phase, 3, 7, 14 days; chronic phase, 1 and 3 months) the regulation of reactive glia and vascular markers. In the hippo-campus, increased expression of mRNA encoding the glial proteins GFAP and Iba1 confirmed neu-roinflammatory status. We report for the first time the concomitant induction in endothelial cells, pericytes and basement membrane of the BBB of specific proteins CD31, PDGFR and ColIV, that peaks at the same time points as inflammation. The altered expression of these proteins occurs ear-ly in TLE, during the latent phase, suggesting that they could be associated with early rupture and pathogenicity of the BBB that will contribute to the chronic phase of epilepsy.

Three different populations of sulfated polysaccharides can be found in the cell wall of the red alga Botryocladia occidentalis. In a previous work, the structures of the two more sulfated polysaccharides were revised. In this work, NMR-based structural analysis was performed on the least sulfated polysaccharide and its chemically modified derivatives. Results have revealed the presence of both 4-linked α- and 3-linked β-galactose units having the following chemical features: more than half of the total galactose units are not sulfated, the α-units occur primarily as 3,6-anhydro-galactose units either 2-O-methylated or 2-O-sulfated, and the β-galactose units can be 4-O-sulfated or 2,4-O-disulfated. SPR-based results indicated weaker binding of the least sulfated galactan to thrombin, factor Xa, and antithrombin, but stronger binding to heparin cofactor II than unfractionated heparin. This report together with our previous publication completes the structural characterization of the three polysaccharides found in the cell wall of the red alga B. occidentalis and correlates the impact of their composing chemical groups with the levels of interaction with the blood co-factors.

The study aimed to showcase how implementing a patient blood management (PBM) program effectively cut unnecessary red blood cell (RBC) transfusions in a New York City urban community teaching hospital. Analyzing seven years from 2013 to 2019, a retrospective review of RBC transfusions was conducted. Following PBM introduction, considerable improvements were observed annually. These included a drop in mean pretransfusion hemoglobin levels from 7.26g/dL (2013) to 6.58g/dL (2019), a 34% reduction in yearly RBC unit transfusions, and fewer units given to patients with pre-Hgb levels ≥7g/dL (1210 units in 2013 to 310 units in 2019). Furthermore, the study noted a decline in two-unit RBC orders when Hgb levels were ≥7g/dL from 65 orders in 2013 to merely 3 in 2019. The estimated total cost-savings attributed to the six-year PBM program duration after full implementation in 2014 amounted to $2.1 million US dollars. Overall, PBM implementation significantly decreased RBC transfusions and enhanced transfusion practices. The findings emphasize that successful PBM strategies don't always necessitate extensive resources or increased budgets but instead rely on the application of intuitive methods, as evidenced by this study.

Sodium glucose cotransporter 2 inhibitors (SGLT2i) are currently available for the management of type 2 diabetes mellitus. SGLT2i act by inhibiting renal SGLT2, thereby increasing glucosuria and lowering serum glucose. Recent trials are emerging supporting a role for SGLT2i irrespective of the diabetic status pointing towards that SGLT2i have other mechanisms of actions beyond blood sugar control. In this review, we will shed light on the role of this group of medications that act as SGLT2i in non-diabetics focusing on pre-clinical and clinical data highlighting the mechanism of renoprotection and effects of SGLT2i in the non-diabetic kidneys.

It is unknown whether postprandial plasma glucose measured from blood taken between 4 and 7.9 h (PPG4-7.9h) is associated with mortality from hypertension, diabetes, or cardiovascular disease (CVD). This study aimed to investigate these associations in 4,896 US adults who attended the third National Health and Nutrition Examination Survey. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of PPG4-7.9h for mortality. This cohort was followed up for 106,300 person-years (mean follow-up, 21.7 years). A 1-natural-log-unit increase in PPG4-7.9h was associated with a higher risk of mortality from hypertension (HR, 3.50; 95% CI, 2.34-5.24), diabetes (HR, 11.7; 95% CI, 6.85-20.0), and CVD (HR, 2.76; 95% CI, 2.08-3.68) after adjustment for all the tested confounders except hemoglobin A1c (HbA1c). After further adjustment for HbA1c, PPG4-7.9h remained positively associated with mortality from hypertension (HR, 2.15; 95% CI, 1.13-4.08) and CVD (HR, 1.62; 95% CI, 1.05-2.51), but was no longer associated with diabetes mortality. Subgroup analyses showed that similar results were obtained in the sub-cohort of participants without a prior diagnosis of myocardial infarction or stroke. In conclusion, PPG4-7.9h predicts mortality from hypertension and CVD independent of HbA1c.

Objective: To explore three novel fasting blood glucose (FBG)-based novel indicators, including FBG-to-albumin ratio (FAR), FBG-to-lymphocytes ratio (FLR), and FBG-to-hemoglobin ratio (FHR), in predicting prognosis and detecting metastasis for patients with pancreatic neuroendocrine neoplasms after resection. Materials and methods: A total of 178 pNEN patients underwent surgical resection were included in this study. Receiver operating characteristic (ROC) curves were used to evaluate the diagnosis values of FAR, FLR, and FHR, and the cut-off values were obtained for further analyses. Univariate and multivariate analyses were conducted to determine the independent predictors. The Kaplan-Meier method was used to evaluate the progression-free survival (PFS) and overall survival (OS) of the pNEN patients. Results: The optimal cut-off values of FAR, FLR, and FHR were 0.17, 2.85, and 0.028, respectively. As for PFS, the area under the curve (AUC) was 0.693 for FAR, 0.690 for FLR, and 0.661 for FHR, respectively. The AUC was 0.770, 0.692, and 0.715 accordingly for OS. The groups with lower FAR, FLR, and FHR were significantly associated with prolonged PFS and OS (p < 0.05). In patients with metastasis, the lower FAR group was correlated with significantly longer PFS and OS (p = 0.022 and 0.002, respectively). The FLR was an independent predictor of PFS in pNEN patients, and the FAR was a predictor of OS. FAR was an independent indicator of PFS in patients with metastasis. Conclusion: Preoperative FAR, FLR, and FHR are effective in predicting the prognosis of pNEN patients and detecting the synchronous metastases.

Background: Sugar laden foods and carbohydrate rich diets with high glycaemic index intake are associated with weight gain, increased incidence of diabetes and is linked with increased cardiovascular risk. A blend of mulberry leaf extract and apple peel extract (Glubloc™) may reduce postprandial blood glucose surge and insulin response following dietary carbohydrate intake by limiting its digestion and uptake from the gut. Methods: In this randomised, placebo-controlled, crossover study, thirty healthy male and female subjects were supplemented with either placebo or Glubloc™, 10 min before a carbohydrate and sugar rich meal intake. Changes in postprandial blood glucose (upto120 minutes) and insulin levels (at 60 minutes) were measured as the primary endpoints. Changes in blood glucose incremental area under the concentration curve (iAUC), maximum concentration (Cmax) and peak time (Tmax) were compared. Results: Thirty adults (mean age 31±7.2 years, BMI 24±3.8 kg/m2) completed the study and the Glubloc™ blend relative to placebo significantly reduced glucose iAUC at 0.5 h (− 38%, p < 0.0003), 1.0 h (− 30%, p = 0.0007), 1.5 h (− 29%, p = 0.0008), and 2.0 h (− 26%, p = 0.002). A statistically significant reduction in 1 h insulin levels (− 35%, p = 0.029) was observed. Conclusion: A single dose supplementation of Glubloc™ significantly reduced the postprandial blood glucose spike and serum insulin levels. The observation of a significant glucose reduction paralleled with a significant lower insulin response supports a reduced gastrointestinal glucose absorption. None of the subjects experienced any major gastrointestinal side effects. This study builds a body of evidence that the combination of white mulberry leaf and green apple peel extracts (Glubloc™) can be a useful supplement to manage postprandial glucose levels, further studies are necessary to evaluate its potential in type 2 diabetes and the regulation of dysglycaemia.

Glioblastoma multiforme (GBM) is a glioma and the most aggressive type of brain tumor with a dismal average survival time, despite the standard of care. One promising alternative therapy is boron neutron capture therapy (BNCT), which is a noninvasive therapy for treating locally invasive malignant tumors, including glioma. BNCT involves boron-10-released radiation directly into tumor cells with minimal damage to healthy tissues. This therapy lacks clinically approved targeted blood-brain-barrier-permeating delivery vehicles for therapeutic drug/ boron-10. Nanoparticles, particularly gold nanoparticles (GNPs), are selective and effective drug-delivery vehicles because of their desirable properties, facile synthesis, and biocompatibility. This review discusses historical and current GNP therapeutic applications as a drug delivery vehicle for treating glioma. Furthermore, GNPs loaded with therapeutic drugs, imaging agents, and GBM-targeting antibodies/ peptides to treat GBM will be discussed. Additionally, the importance of upper and lower limits on therapeutic efficacy will be described and explored followed by highlighting their advantages, limitations, and possible toxicity. Recent research and selected important findings for GNP-mediated pharmaceutics in GBM will also be considered.

Cellular therapies have started an important new therapeutic direction for Autistic Spectrum Disease (ASD), and the ample diversity of ASD pathophysiology and the different types of cell therapies need an equally ample effort for studying the applicable ASD causes and the specific benefits of cell therapies via clinical studies.CORDUS Clinical Study is a crossover study in which autologous cord blood was administered intravenously to 56 patients between January 2019 and July 2023, and has compared its efficacy versus an individualized combination of supplements; both treatments were administered in a different sequence to all participants. Treatment efficacy was evaluated pre- and post- treatments by an independent psychotherapist with ATEC, Q-CHAT and a 16-item comparative table score, after interviews with the children’s parents and therapists.Cord blood was beneficial in the group of 3–7-year-old children (n=28; 3 out of 4 children – 78.57% - improved scores), but was much less effective in kids older than 8 years or with body weight of more than 35 kg (n=28; 1 out of 10 children improved scores). Individualized supplements were more efficacious than cord blood in 5 cases out of 28, while in 23 kids cord blood brought more improvement than supplements; 6 kids registered minor or no improvement. Statistically significant improvements were seen after cord blood infusion on areas such as verbalization and social interaction, but not on irritability or aggressive behavior; also ample individual differences were noted. No serious adverse reactions were noted during and after cord blood or supplement administration.

Keywords: COVID-19, severity, influenza, serum antibodies, blood tests

Oxygen extraction fraction (OEF), the fraction of oxygen that tissue extracts from blood, is an es-sential biomarker for directly assessing tissue viability and function in neurologic disorders. For quantitative mapping of OEF, an integrative model of quantitative susceptibility mapping and quantitative blood oxygen level-dependent magnitude (QSM+qBOLD or QQ) was recently pro-posed. However, QQ assumes Gaussian noise in both susceptibility and multi-echo gradient echo (mGRE) magnitude signals for OEF estimation. This assumption is unreliable in low sig-nal-to-noise ratio (SNR) regions like disease-related lesions, risking inaccurate OEF estimation and potentially impacting clinical decisions. Addressing this, our study presents a novel multi-echo complex QQ (mcQQ) that models realistic noise in mGRE complex signals. The proposed mcQQ was implemented using a deep learning framework (mcQQ-NET) and compared with the existing deep learning-based QQ (QQ-NET) in simulations, ischemic stroke patients, and healthy subjects. Both mcQQ-NET and QQ-NET used identical training and testing datasets and schemes for a fair comparison. In simulations, mcQQ-NET provided more accurate OEF than QQ-NET. In the sub-acute stroke patients, mcQQ-NET showed a lower average OEF ratio in lesions relative to unaf-fected contralateral normal tissue than QQ-NET. In the healthy subjects, mcQQ-NET provided uniform OEF maps, similar to QQ-NET, but without unrealistically high OEF outliers in areas of low SNR. Therefore, mcQQ-NET improves OEF accuracy by better reflecting realistic data noise characteristics.

Accurate geometric modeling of blood vessels lumen given their 3D images is a basis for vessel quantification in support of cardiovascular diseases diagnosis, treatment and monitoring. Unlike other approaches, which assume circular or elliptical vessel cross-section, the proposed method employs parametric B-splines combined with the image formation system equations to accurately localize the highly curved lumen boundaries. No image segmentation is involved which might reduce the localization accuracy in effect of spatial discretization. It is shown that the model parameters can be reliably identified by a feedforward neural network which, driven by the cross-section images, predicts the parameter values many times faster than a reference least-squares (LS) model fitting algorithm. Two example applications: modeling the lower extremities artery-vein complexes visualized in steady-state contrast-enhanced magnetic resonance images (MRI) and the coronary arteries pictured in computed tomography angiograms (CTA), are presented and discussed to demonstrate the method potential. Besides application to medical diagnosis, blood-flow simulation and vessel-phantom design, it can serve as a tool for automated annotation of image datasets required to train machine-learning algorithms.

Extramedullary hematopoiesis is a compensatory response in chronic hemolytic anemia, such as thalassemia, and can lead to spinal cord compression. This case report describes a 36-year-old woman with β-thalassemia who presented with lower extremity motor deficiency, pelvic paresthesia, and bladder dysfunction. The patient had a history of low back pain, bilateral lower limb weakness, and poor compliance with iron chelation therapy. MRI revealed compression of the spinal cord due to extramedullary hematopoiesis. Surgical intervention was not feasible, and the patient underwent hypertransfusion and iron chelation therapy. Neurological symptoms improved, but urinary retention persisted. The patient continues to receive iron chelation treatment and undergoes transfusions. Extramedullary hematopoiesis is a common complication in thalassemia and requires an individualized treatment approach.

One of the hallmarks of Alzheimer’s disease (AD) is the accumulation of beta-amyloid peptide (Aβ) leading to formation of soluble neurotoxic Aβ oligomers and insoluble amyloid plaques in various parts of the brain. Aβ undergoes post-translational modifications that alter its pathogenic properties. Aβ is produced not only in brain, but also in the peripheral tissues. Such Aβ, including its post-translationally modified forms, can enter the brain from circulation by binding to RAGE and contribute to the pathology of AD. However, the transport of modified forms of Aβ across the blood–brain barrier (BBB) has not been investigated. Here, we used a transwell BBB model as a controlled environment for permeability studies. We found that Aβ42 containing isomerized Asp7 residue (iso-Aβ42) and Aβ42 containing phosphorylated Ser8 residue crossed the BBB better than unmodified Aβ42, which correlated with different contribution of endocytosis mechanisms to the transport of these isoforms. Using microscale thermophoresis, we observed that RAGE binds to iso-Aβ42 an order of magnitude weaker than to Aβ42. Thus, post-translational modifications of Aβ increase the rate of its transport across the BBB and modify the mechanisms of the transport, which may be important for AD pathology and treatment.

Introduction: In recent years, platelets have been in short supply and high demand. Approximately one in five cardiac surgery patients require platelets. In our safety-net hospital, however, the incidence is over 40%. Renal dysfunction, long cardiopulmonary bypass (CPB) times, and absence of tranexamic acid (TXA) are common risk factors for requiring platelet transfusions. Methods: Our hypothesis was fewer platelets would be transfused within two hours after bypass under these three conditions: creatinine is low, predicted surgery duration is short, and TXA is uniformly administered. Our anesthesia department designed this retrospective before-and-after observational study when the surgery department decided to narrow preoperative criteria respective to these three elements. The Institutional Review Board of Louisiana State University Health Sciences Center Shreveport approved of the protocol and waived individual informed consent. We compared timing of platelet transfusions (within 7 days) in consecutive patients who had CPB during the first ninety days of 2022 to those in 2023 using t-tests in SAS 9.3. Confounders included age, weight, anticoagulants, gender, and the platelet counts and hemoglobin immediately prior to platelet transfusion. Secondary outcomes were postoperative day two creatinine and other components transfused. Results: Preoperatively creatinine tended to be higher in 2022 at 1.5 vs 1.1, reaching significance postoperatively at 1.9 vs 1.1 (p=0.02). Bypass times decreased from 174 to 124 minutes (p=0.06). TXA use increased from 18 of 28 to 26 of 29 patients. Platelet counts increased on bypass from 142 to 173 (p=0.06). Platelet and hemoglobin nadirs were higher (day 3: 8g/dL vs 8.8, p=0.04; 98 vs 138, p=0.005). Platelet units transfused per patient tended to increase (0.75+/-1 vs 0.93+/-1.5); if exposed, patients tended to receive more units (2.1+/-1.3 vs 2.5+/-1.4) sooner. Changes in transfusions for red cells were nonsignificant at 1.97 per patient to 1.21, cryoprecipitate 0.36 to 0.69, and FFP 0.93 to 0.83. Conclusions: This is the first study examining timing of platelet transfusions after bypass. In the present investigation, we measured platelet count during bypass and prothrombin hours after arrival in the intensive care. Platelets were often administered in sets of two because of scarce immediate supply, partly from lack of an agitator table. More importantly, these data support a need for point-of-care thromboelastograms intraoperatively, but the cost has been prohibitive. Some centers’ algorithms list triggers for transfusion by fibrinogen and prothrombin times, available immediately after separation from bypass.

Cardiotonic steroids (CTS) are a group of steroid compounds derived from certain plants and animals. CTS are selective inhibitors of Na,K-ATPase, so for a long time they were widely used for medical purposes to treat heart failure and some other diseases. However, over time, doctors gradually began to refuse this group of drugs due to their narrow therapeutic range and a number of serious side effects. However, in parallel with the rise and fall of interest in CTS as a drug, interest in them as a single class of high-affinity Na,K-ATPase inhibitors has only increased. Numerous data on the effect of CTS on signaling cascades and cell viability made impelling a search for a rationale for the existence of such a subtle biological regulator. A large number of studies devoted to the potential use of CTS in the treatment of neurodegenerative, oncological, immune and other diseases "revitalized" the already "written off" group of the drugs. If initially the role of exogenous (mainly plant origin) CTS was studied, then by the 90s of the XX century the study of the role of endogenous CTS and their regulatory effects became a popular trend in biology and physiology. The role of endogenous CTS was studied in details in the pathogenesis of cardiovascular diseases [1]. A large number of researchers have unanimously stated that endogenous CTS are very complex regulators of the development of pathological processes; however, the exact cause-and-effect relationship that would unambiguously explain the processes of synthesis, utilization, and the role of endogenous CTS has not yet been established. The effects of CTS in the frame of various regulatory schemes have been described, but the predominant number of studies was devoted to arterial hypertension, heart and renal failure, cancer [2–4], aging [5,6], and neuroinflammation. The effects of both endo- and exogenous CTS on blood cells and have been studied to a much lesser extent.

Background: Mounting evidence supports the role of the endocannabinoid system in neurophysiology, includ-ing blood-brain barrier (BBB) function. Recent work has demonstrated that activation of endocannabinoid re-ceptors can mitigate insults to the BBB during neurological disorders, like traumatic brain injury, cortical spreading depression and stroke. As alterations to the BBB are associated with worsening clinical outcomes in these conditions, studies herein sought to examine the impact of endocannabinoid depletion on BBB integrity. Methods: Barrier integrity was investigated in vitro via bEnd.3 cell monolayers to assess endocannabinoid syn-thesis, barrier function, calcium influx, junctional protein expression, and proteome-wide changes. Results: In-hibition of 2-AG synthesis using DAGLα inhibition and siRNA inhibition of DAGLα led to loss of barrier in-tegrity via altered expression of VE-cadherin, which could be partially rescued by exogenous application of 2-AG. Moreover, the deleterious effects of DAGLα inhibition on BBB integrity showed both calcium and PKC (protein kinase C)-dependency. Conclusions: These data indicate that disruption of 2-AG homeostasis in brain endothelial cells, in the absence of insult, is sufficient to disrupt BBB integrity thus supporting the role of the endocannabinoid system in neurovascular disorders.

Abstract: Placenta accreta spectrum (PAS) is a severe complication of pregnancy associated with excessive invasion of cytotrophoblast cells at the sites of the endometrial-myometrial interface and the myometrium itself in cases of adherent (creta) and invasive (increta and percreta) forms, respectively. Despite advancements in ultrasound protocols and found associations of alpha-fetoprotein, PAPP-A, hCG, PLGF, sFlt-1, IL-8, and IL-33 peripheral blood levels with PAS, the condition remains undiagnosed before delivery because of the lacking clear evaluation criteria for each of the three grades of PAS. This leads to a high risk of massive blood loss, maternal hysterectomy, and preterm birth. While using deep sequencing, miRNA signatures of placental tissue, myometrium, and blood plasma from women with PAS in the third trimester of pregnancy, as well as miRNA profile in exosomes from the blood serum of women in the first trimester with physiologically progressing pregnancy, complicated by PAS or preeclampsia, were obtained. Two logistic regression models were constructed, both featuring statistically significant parameters related to the levels of miR-26a-5p, miR-17-5p, and miR-101-3p quantified by real-time PCR in native blood serum. These models demonstrated 100% sensitivity in detecting PAS during the first pregnancy screening. These miRNAs were identified as specific markers for PAS, showing significant differences in their blood serum levels during the first trimester in the PAS group compared to those in physiological pregnancies, early- or late-onset preeclampsia groups. Furthermore, these miRNAs exhibited differential expression in the PAS placenta and/or myometrium in the third trimester and, according to literature data, control angiogenesis. Significant correlations were found between extracellular hsa-miR-101-3p and nuchal translucency thickness, hsa-miR-17-5p and uterine artery pulsatility index, and hsa-miR-26a-5p and hsa-miR-17-5p with PLGF. The developed test system for early non-invasive PAS diagnosis based on the blood serum level of extracellular miR-26a-5p, miR-17-5p, and miR-101-3p can serve as an auxiliary method for 1st trimester screening pregnant women, subject to validation on independent test samples.

. Cucurbiturils are a family of macrocyclic oligomers capable of forming host-guest complexes with various molecules. Due to noncovalent binding to drug molecules and low toxicity, cucurbiturils has been extensively investigated as a potential carrier for drug delivery. However, the immune system interactions with different drug carriers, including cucurbiturils, are still under investigation. In this study, we focused on cucurbiturils immunosafety and immunomodulation properties in vivo. We measured blood counts, lymphocyte subpopulations in blood, spleen, and bone marrow, and assessed in vivo toxicity to spleen and bone marrow cells after intraperitoneal administration to mice. We also evaluated the effect of cucurbiturils on cellular and humoral immune responses. Cucurbiturils in high concentrations effect on the immune system in vivo. The action of various cucurbiturils differs in different homologues, which, apparently, is associated with different interactions in the internal environment of the body.

The liver health of Gilthead sea bream and European sea bass fed fishmeal-free diets including various proportions of plant proteins, insect and poultry by-product meals, was investigated through biochemical and histological analyses using a new Liver Index (LI) formula. Four isoproteic (45% DM) and isolipidic (20% DM) diets were compared: a control, plant-based diet (CV) and other three test ones where 40% of a plant protein-rich ingredient mixture was replaced by Hermetia illucens (H40) or poultry by-product (P40) meals alone or in combination (H10P30). The trials lasted 12 and 18 weeks for sea bream and sea bass, respectively. The results so far ob-tained highlighted species-specific differences in the physiological response to dietary changes. In sea bream, the biochemical and histological responses suggest favorable physiological status and liver health, with higher serum cholesterol (CHO) and triglyceride (TAG) levels and moderate hepatocyte lipid accumulation with the H10P30 diet compared to CV (p<0.05). In sea bass, all diets resulted in elevated serum TAG levels and liver lipid accumulation particularly in fish fed the P40 one (p<0.05) which resulted in the highest LI, coupled with higher frequency of severe lipid accumulation, hypertrophy, cord loss, peripheral nuclei displacement and pyknosis. In conclusion sea bream well adapted to the test diets, while sea bass exhibited altered hepatic lipid metabolism leading to incipient liver steatosis, likely due to the high lipid content of the diets including the insect and poultry meals. The LI developed in this study proved to be a reliable tool for assessing the effects of dietary changes on liver health of sea bream and sea bass, consistent with biochemical and histological findings.

Circulating miRNA-451a has recently emerged as an important biomolecule with potential clinical values as a diagnostic marker for several diseases. However, to be used as such, it is critical to accurately assay miRNA-451a in the clinic. Yet, pre-analytical factors that can affect such an error-free clinical assay of miRNA-451a have not been explored. This study aimed at investigating several of these pre-analytical factors that may affect the accurate quantification of miRNA-451a in human blood samples. We initially evaluated miRNA-451a levels in red blood cells (RBCs), white blood cells (WBCs), platelets, and plasma by droplet digital PCR (ddPCR). Next, we quantified miRNA-451a levels in whole blood or plasma stored at different temperatures for different time periods by ddPCR and used hemolyzed plasma samples to study the effects of hemolysis on plasma miRNA-451a concentration. We found that WBCs and platelets contain trace amounts of miRNA-451a and that about 99.9% of miRNA-451a in the blood are localized in RBCs. Hemolyzed plasma showed 58.5-fold increase in miRNA-451 concentration as compared to non-hemolyzed plasma. Importantly, plasma stored at room temperature (RT) or 4ºC showed a steady statistically significant decrease in miRNA-451a levels over a 7-day period whereas plasma samples stored at -20 or -80ºC for up to 7 days showed stable miRNA-451a levels. Together, our data indicate that hemolysis and blood storage at RT or 4ºC may have significant negative effects on the levels of circulating miRNA-451a.

Blood-derived products (BP) like citrate-platelet-rich plasma (CPRP) or hyperacute serum (HAS) are known to contain many growth factors. Combined mitogenic and DNA damaging stimuli might lead to increased senescent cell burden and altered senescence-associated secretory pheno-type (SASP). Therefore, the senescent state was extensively tested by γH2AX staining, p21 Q-PCR and western blot, growth curves and senescence associated ß-galactosidase staining. Two main treatments with BP were performed early (immediately after etoposide) and late (after addition-al 11days). Effects of the BP treatment was evaluated by IL-6 and IL-8 measurement as well as collagen (COL1) and p21 mRNA expression. Additionally, XTT assays, cell size measurements, viability assays, and cell number calculations were performed. HAS treated cells in early treat-ment had the lowest observed IL-6 and IL-8. In contrast, there was a clear inflammatory response for IL-8 on HAS and CPRP treated cells in late treatment. For COL1 expression an upregulation in early treatment could be shown, meanwhile cells in the late treatment group remained unaf-fected. In CPRP treated cells, the COL1 expression decreased. All in all, BP treatment seems to have slightly positive effects regarding skin rejuvenation.

This study investigates the suitability of the timestamp approach algorithm for predicting blood pressure (BP) using wearable and comfortable devices, showcasing its accuracy even with low-frequency sampled signals. Developed within the SINTEC European project, the algorithm utilizes Electrocardiogram (ECG) and Photoplethysmogram (PPG) sensors, demonstrating promising results in both laboratory and hospital settings. The research emphasizes the algorithm’s potential to transform continuous and non-invasive BP monitoring through wearable technology, offering frequent measurements with minimal discomfort. While the study shows promise, further exploration is needed, focusing on optimizing machine learning coefficients for long-term monitoring applications and addressing potential changes over time. Technological improvements, including the implementation of edge computing algorithms, hold the key to enhancing BP accuracy, denoising techniques, and integrating alarm systems for future wearable solutions. This study emphasizes the adaptability of the algorithm for diverse healthcare environments, paving the way for broader applications in convenient and reliable BP monitoring.

The lack of accurate and feasible diagnostic tests poses a significant challenge to visceral leish-maniasis (VL) healthcare services in endemic areas. To date, various VL diagnostic tests have been or are being developed, and their diagnostic performance needs to be assessed.. In the present study, the diagnostic performance of rk39RDT, Direct Agglutination Test (DAT), Microscopy, Loop Mediated Isothermal Amplification (LAMP), and miniature direct-on-blood polymerase chain reaction - nucleic acid lateral flow immunoassay (mini-dbPCR-NALFIA) was assessed using quantitative polymerase chain reaction (qPCR) as reference test in an endemic region of Ethiopia. In this study, 235 patients VL suspected patients and 104 non-endemic healthy controls (NEHC) were recruited. Among the VL-suspected patients, 144(61.28%) tested positive with qPCR. Sensi-tivities for rk39 RDT, DAT, Microscopy, LAMP assay, and mini-dbPCR-NALFIA were 88.11%, 96.50%, 76.58%, 94.33%, and 95.80%, respectively. Specificities were 83.33%, 97.96%, 100%, 97.38%, and 98.92% for rk39 RDT, DAT, Microscopy, LAMP assay, and mini-dbPCR-NALFIA, respectively. In conclusion, Rk39 RDT and microscopy exhibited lower sensitivity, while DAT demonstrated excellent performance. LAMP and mini-dbPCR-NALFIA showed excellent perfor-mance with feasibility to implement in remote endemic areas, although the latter requires further evaluation in such regions.

(1) Background: Neonatal early-onset sepsis (EOS) is associated with important mortality and morbidity. The aims of this study were to evaluate the association between serum biomarkers with early onset neonatal sepsis in a cohort of patients with prolonged rupture of membranes (PROM), and to calculate their diagnostic accuracy. (2) Methods: A retrospective cohort study was conducted on 1355 newborns with PROM admitted between January 2017 and March 2020, who were divided in two groups: group A, with PROM ≥ 18 hours and group B, with PROM < 18 hours. Both groups were further split into subgroups: proven sepsis, probable sepsis and no sepsis. Descriptive statistics, ANOVA analysis, and a Random Effects Generalized Least Squares (GLS) regression were used to evaluate the data. (3) Results: The statistically significant predictors of neonatal sepsis were the high white blood cells count from the first (p = 0.005) and third day (p = 0.028), and high CRP values from the first day (p = 0.004). Procalcitonin (area under the curve - AUC = 0.78) and CRP (AUC = 0.76) measured on the first day had the best predictive performance for early onset neonatal sepsis. (4) Conclusions: Further studies are needed to explore other bi-omarkers of sepsis in both pregnant women and newborns to better predict EOS.

In Southeast Asia, the incidence of Leukemia, a malignant blood cancer originating from hema-topoietic progenitor cells, is on the rise, marked by a concerning 54% mortality rate. This study focuses on enhancing early-stage prediction to improve patient recovery prospects significantly. Leveraging Machine Learning and Data Science, we employ protein sequential data from frequently mutated genes such as BCL2, HSP90, PARP, and RB to predict Chronic Myeloid Leukemia (CML). Our approach relies on robust feature extraction techniques, namely Di-peptide Composition (DPC), Amino Acid Composition (AAC), and Pseudo amino acid composition (Pse-AAC), with prior attention to addressing outliers and validating feature selection through the Pearson Corre-lation Coefficient. Data augmentation ensures a well-rounded dataset for analysis. Employing a range of Machine Learning models, including Support Vector Machine (SVM), XGBoost, Random Forest (RF), K Nearest Neighbor (KNN), Decision Tree (DT), and Logistic Regression (LR), we achieve accuracy rates spanning from 66% to 94%. These classifiers undergo comprehensive as-sessment using performance metrics such as accuracy, sensitivity, specificity, F1-score, and the confusion matrix. Our proposed solution, encompassing a user-friendly web application dashboard, presents an invaluable tool for early CML diagnosis with profound implications for practitioners, offering a deploy-able asset within healthcare institutions and hospitals.

Prediabetes, a pivotal phase in glucose metabolism between normalcy and diabetes, exerts a profound influence on the aging process and the risk of age-related diseases. This comprehensive review delves into the intricate web of blood-based biomarkers that collectively expedite senescence, marking the transition from a state of health to age-related complications. Key findings underscore the significance of diverse biomarkers, such as telomere length, p16INK4a, senescence-associated secretory phenotype (SASP) factors, DNA methylation clocks, advanced glycation end products (AGEs), inflammatory and oxidative stress markers, circulating hormones, and additional factors like folate, B12, osteocalcin, and more. Not only do these biomarkers serve as indicators of senescence, but they actively fuel chronic inflammation, oxidative stress, and metabolic dysregulation, all of which contribute to accelerated aging. The implications of this understanding are profound, as prediabetes emerges as a critical period in an individual's life, influencing various physiological systems, including the vascular and neural systems, metabolic functions, hormonal regulation, and bone health. Recognizing the profound influence of prediabetes on senescence provides a foundation for personalized intervention strategies to mitigate age-related complications and promote healthy aging. Future research directions call for a more diverse array of biomarkers, in-depth exploration of their roles, and the development of tailored precision medicine strategies to ensure a holistic understanding and effective management of prediabetes-induced senescence and its implications for aging. This knowledge has far-reaching implications for public health and clinical practice, emphasizing the need for early detection and intervention in prediabetic individuals to enhance the quality of life in an aging population with diverse needs.

. Background: regular exercise elicits adaptive changes from several organs and physiological processes, including erythrocyte properties. Methods: in a group of 79 subjects (62 men and 17 women; mean age 31.37 +/- 10.19 years) who trained several times a week as they practiced amateur sports, we evaluated the elongation index, marker of erythrocyte deformability, the red blood cell distribution width (RDW), indicator of erythrocyte anisocytosis, hematocrit, hemoglobin and the main erythrocyte indices (MCV, MCH, MCHC) in basal conditions. Results: in comparison with a group of healthy not trained volunteers, the values of the elongation index, and not the RDW, are increased and this datum is accompanied by an increase of MCV and MCHC, likely related to an increased presence of circulating young erythrocytes in trained subjects. We also divided the same group according to the median of the VO2max, observing that the subgroup above the median shows both an increase in the elongation index values and a decrease in MCH and MCHC. Conclusions: in trained subjects there is no correlation between the values of elongation index and the RDW, while of particular interest and of a certain complexity seem the interrelations among elongation index, RDW and the main erythrocyte indices.

My hypothesis is that the signs and symptoms of Long COVID can be explained by a shortage of blood in the body and a resulting deficient blood flow through nearly all organs. This shortage arises through damage to the blood-producing organs during the acute phase, while the breakdown of blood continues as normal, after an initial increase. In order to ensure the perfusion of organs that are directly necessary for survival, the body takes the emergency measure of diverting blood from other organs and tissues. The perfusion of the blood-producing organs is also affected by this distribution measure, which hinders the smooth recovery of the total blood volume. The body is stuck in this vicious circle: a shortage of circulating blood hinders the recovery of blood production. This explains the long duration of Long COVID. My proposed treatment of Long COVID focuses on the recovery of the correct volume of blood in the body of the right composition by the very careful administration of donor blood products under continuous expert supervision. A trial treatment can be performed in any hospital without much additional preparations, and has a lower associated risk for the patient than analysing the total blood. A diagnosis ex juvantibus, by therapeutic response, is therefore preferable, and will result in the healing process starting earlier. Indications in blood laboratory values of a shortage of blood are a high serum ferritin due to internal breakdown of blood and values for haematocrit and albumin at reciprocal extremes of the reference ranges due to a stagnation of blood production.

Background: Deoxycholic acid (DCA) is a secondary bile acid produced by gut bacteria. Its serum concentration increases in cardiovascular disease (CVD). We hypothesized that DCA may affect hemodynamic parameters in rats. Methods: The concentration of DCA in systemic blood was measured with liquid chromatography coupled with mass spectrometry. Arterial blood pressure (BP), heart rate (HR) and echocardiographic parameters were evaluated in anesthetized, male, 3-4-month-old Sprague-Dawley rats administered intravenously (IV) or intracerebroventricularly (ICV) with investigated compounds. Mesenteric artery (MA) reactivity was tested ex vivo. Results: The baseline plasma concentration of DCA was 0.24 ± 0.03 mg/l. The oral antibiotic treatment produced a large decrease in the concentration. Administered IV, the compound increased BP and HR in a dose-dependent manner. DCA also increased heart contractility and cardiac output. None of the tested compounds: prazosin (an alpha-blocker), propranolol (beta-adrenolytic), atropine (muscarinic receptor antagonist), glibenclamide (K-ATP inhibitor) or DY 268 (FXR antagonist), glycyrrhetinic acid (11HSD2 inhibitor) significantly diminished the DCA-induced pressor effect. ICV infusion did not exert significant HR or BP changes. DCA relaxed MAs. Systemic vascular resistance did not change significantly. Conclusions: DCA increases BP by increasing cardiac output. As a bioactive gut bacteria-derived metabolite, DCA may co the interaction between gut microbiota and the host’s circulatory system.

Ischemia, the inadequate blood flow, can arise from pre-existing or traumatic events, remain an undetectable issue, and impact the body's ability to provide oxygen to necessary limbs, organs, muscles, or tissue. New technology involving wearable ultrasonic devices allows medical professionals to gain real-time insight into the cardiovascular system of their patients. A non-invasive, postage-stamp-sized ultrasonic sensor can be attached to a patient, allowing for continuous monitoring of the patient’s blood pressure outside of the hospital. After reviewing 16 papers on ultrasonic sensors, this paper intends to review the current use of wearable ultrasonic sensors and the advantages and limitations of the technology used to obtain accurate blood pressure readings. This review will bring attention to the evolving and expanding world of wearable ultrasonic sensors for medical applications.

In this paper, we redefine the boundaries of blood cell classification, expanding from 5 to 11 distinct blood cell types using the challenging 11-class PBC dataset. This shift enables a deeper understanding of blood cell diversity, overcoming previous limitations in medical image analysis. Our approach combines state-of-the-art deep learning techniques, including pre-trained ConvNets, ViTb16 models, and custom CNN architectures. We employ transfer learning, fine-tuning, and ensemble strategies, such as CBAM and Averaging ensembles, to achieve unprecedented accuracy and interpretability. Our fully fine-tuned EfficientNetV2 B0 model sets a new standard, with a macro-average precision, recall, and F1-score of 91%, 90%, and 90%, respectively, and an average accuracy of 93%. This breakthrough underscores the transformative potential of 11-class blood cell classification for more precise medical diagnoses. Moreover, our groundbreaking "Naturalize" augmentation technique produces remarkable results. The 2K-PBC dataset generated with "Naturalize" boasts a macro-average precision, recall, and F1-score of 97%, along with an average accuracy of 96% when leveraging the fully fine-tuned EfficientNetV2 B0 model. This innovation not only elevates classification performance but also addresses data scarcity and bias in medical deep learning. Our research marks a paradigm shift in blood cell classification, enabling more nuanced and insightful medical analyses. The "Naturalize" technique’s impact extends beyond blood cell classification, emphasizing the vital role of diverse and comprehensive datasets in advancing healthcare applications through deep learning.

The blood–brain barrier (BBB) plays pivotal roles in synaptic and neuronal functioning by sealing the space between adjacent microvascular endothelial cells. BBB breakdown is present in patients with mild cognitive impairment (MCI) or Alzheimer disease (AD). Claudin-5 (CLDN-5) is a tetra-spanning protein essential for sealing the intercellular space between adjacent endothelial cells in the BBB. In this study, we developed a blood-based assay for CLDN-5 and investigated its diagnostic utility by using 100 cognitively normal (control) subjects, 100 patients with MCI, and 100 patients with AD. Plasma CLDN-5 levels were increased in patients with AD (3.08 ng/mL) compared with controls (2.77 ng/mL). Plasma levels of phosphorylated tau (pTau181), a biomarker of pathological tau, were elevated in patients with MCI or AD (2.86 and 4.20 pg/mL, respectively) compared with control subjects (1.81 pg/mL). In patients with MCI or AD, plasma levels of CLDN-5—but not pTau181—decreased with age, suggesting some age-dependent BBB changes in MCI and AD. These findings suggest that plasma CLDN-5 may a potential biochemical marker for the diagnosis of MCI and AD.

In this observational study, we compared continuous physiological signals during an active stand test in adults aged 50 years and over, characterized as frail by three different criteria, using data from The Irish Longitudinal Study on Ageing (TILDA). Four independent groups were identified: those characterized as frail only by one of the frailty tools used (the physical Frailty Phenotype (FP), the 32-item Frailty Index (FI), or the Clinical Frailty Scale (CFS) classification tree), and a fourth group where participants were not characterized as frail by any of these tools. Continuous non-invasive physiological signals were collected during an active stand test: systolic (sBP) and diastolic (dBP) blood pressure, as well as heart rate (HR), using digital artery photoplethysmography. Additionally, frontal lobe cerebral oxygenation (Oxy), deoxygenation (Deoxy), and tissue saturation index (TSI) were also non-invasively measured using near-infrared spectroscopy (NIRS). The signals were visualized across frailty groups and statistically compared using one-dimensional statistical parametric mapping (SPM). A total of 1,124 participants (mean age 63.5 years, 50.2% women) were included: 23 were characterized as frail only by FP, 97 by FI, 38 by CFS, and 966 by none of these criteria. SPM analyses revealed that only the group characterized as frail by FI had significantly different signals (p<0.05) compared to the non-frail group. Specifically, they exhibited a lesser increase in HR between 5-15 seconds post-stand and larger deficits in sBP and dBP between 15-40 seconds post-stand, and possibly a lower Delta TSI at 20 seconds post-stand. In this comparison, the FI proved more adept at capturing distinct physiological responses to standing, likely due to its direct inclusion of cardiovascular morbidities in its definition.

Background: Along with sarcopenia, delayed blood pressure (BP) recovery after standing and orthostatic hypotension (OH) are among key clinical challenges associated with ageing. Previous studies have reported an association between sarcopenia and delayed orthostatic BP recovery and OH. However, the haemodynamic mechanisms underlying this association remain unclear. Methods: 107 attendees to a falls and syncope clinic aged 50+ years underwent an active stand test with non-invasive beat-to-beat haemodynamic measurement. Hand grip strength and 5-chair stands time were measured. Muscle mass was estimated using bioelectrical impedance analysis, and participants were classified as non-sarcopenic and sarcopenic. Mixed effects models with linear splines were used to model the effect of sarcopenia status on Modelflow®-derived mean arterial pressure (MAP), cardiac output (CO), total peripheral resistance (TPR), stroke volume (SV) and heart rate (HR) after standing, while controlling for potential confounders. Results: Sarcopenia was associated with: attenuated recovery of MAP in the 10-20s period after standing (β -0.67, P<0.001); attenuated rise to peak (0-10s) and recovery from peak (10-20s) of CO (β -0.05, P<0.001; β 0.06, P<0.001); attenuated recovery (10-20s) of TPR from nadir (β -0.02, P<0.001) and attenuated recovery from peak (10-20s) of SV (β 0.54, P<0.001). HR was not significantly associated with sarcopenia status at any time interval after standing. Conclusion: The attenuated BP recovery after standing seen in sarcopenia appears to be driven by initial diminished peak of CO followed by attenuated recovery of CO from peak and TPR from nadir. The CO finding appears to be driven by SV rather than HR. Potential mechanisms for these findings include: cardio-sarcopenia, the effects of sarcopenia on the autonomic nervous system and/or the skeletal muscle pump.

Blood testing is a crucial application in the field of clinical studies for disease diagnosis and screening, biomarkers discovery, organ function assessment, and personalized medication. Therefore, it is of utmost importance to collect precise data in a short time. In this study, we utilized Raman spectroscopy to analyze blood samples and extracted comprehensive biological information, including the primary components and compositions present in the blood. We conducted short-wavelength (532 nm green light) Raman scattering spectroscopy on blood samples, plasma, and serum, and subsequently analyzed the biological characteristics detected in each sample type. Our results indicated that whole blood had high hemoglobin content, which suggests that hemoglobin is a major component of blood. The characteristic Raman peaks of hemoglobin were observed at 690, 989, 1015, 1182, 1233, 1315, and 1562–1649 cm−1. Analysis of plasma and serum samples indicated the presence of β-carotene, which exhibited characteristic peaks at 1013, 1172, and 1526 cm−1. Additionally, in the field of medical blood testing, the novel 3D Silicon micro-channel device technology holds immense potential. It can serve as a substrate and helps to detect various diseases and biomarkers, providing real-time data to help medical professionals and patients better understand their health conditions. Changes in biological data collected in this manner could potentially be used to diagnose clinical diseases.

The aim of the present study, was to evaluate the wild freshwater fish health status using a vast array of biomarkers as predictive factor of pollutant exposure. European eel (Anguilla anguilla) and Brown trout (Salmo trutta fario), resident in rivers with different degree of pollution in the South of Italy (Picentino river with good environmental quality and Tusciano river with low environmental quality), were examined using biometric parameters, histopathological and immunohistochemical biomarkers to evaluate the health status and a possible correlation with the water quality. Several alterations identified in the liver positively correlated with water and soil pollutants were: hemorrhage (P≤0.05), cytoplasmic vacuolization (P≤ 0.01), hemosiderosis (P≤0.05), irregular arrangement of hepatocytes (P≤ 0.01), lipid accumulation (P≤0.05), necrosis (P≤ 0.01), cellular hyperplasia (P≤0.05), leukocyte infiltration (P≤ 0.01) and melanomacrophages centers (MMC) (P≤ 0.01). In the spleen, only hemosiderosis correlated with water and soil pollutants (P≤ 0.05). The inflammatory biomarker tumor necrosis factor α (TNFα) and ciclooxigenase 2 (COX2) responded to the environmental pollution, as well as the oxidative stress biomarkers superoxide dismutase (SOD) and 8-Hydroxy-2'-deoxyguanosine (8-OHdG). Erythrocytic nuclear abnormalities and erythrocytic cellular abnormalities were found significantly higher in the blood of both Europen eel (P&lt;0.0001) and Brown trout (P &lt;0.001) in the Tusciano river with respect to the Picentino river. Taken together, these results outline the need to increase the number of suitable biomarkers to assess fish health and reinforce the importance to employ additional biomarkers in biomonitoring programs which can be applied to evaluate the water quality and environmental risk assessment around the world

Angiotensin-converting enzyme (ACE)1, ACE2, and renin are components of the renin-angiotensin system (RAS), which regulates blood pressure. ACE2 also serves as a receptor for SARS-CoV-2 and together with the transmembrane serine protease 2 (TMPRSS-2), mediates viral cell-endocytosis. As the placenta expresses all these factors, it acts as a target for SARS-CoV-2 and also as a source of blood pressure modulators. An ACE1/ACE2 ratio imbalance can lead to RAS dysregulation and a bad prognosis in COVID-19 patients. Calcitriol, the vitamin D active metabolite, negatively regulates RAS, reduces inflammation, and enhances antiviral immunity, thereby playing a protective role against COVID-19 severity. Placental calcitriol has been inversely correlated with maternal blood pressure; however, its regulatory role in RAS components and SARS-CoV-2 receptors within the fetomaternal unit has been barely explored. Therefore, we investigated the effects of calcitriol on placental RAS components. Calcitriol downregulated ACE1, ACE2, TMPRSS-2, and renin gene expression in cultured syncytiotrophoblasts and the extravillous trophoblast cell line HTR-8/SVneo. The ACE1/ACE2 ratio was also downregulated by calcitriol. Similar results were obtained in syncytiotrophoblasts treated with calcidiol, the precursor of calcitriol. Altogether, these results support that vitamin D is essential in restricting SARS-CoV-2 placental infection while helping to regulate maternal blood pressure during pregnancy.

Previous studies detail that the different blood groups are associate to incidence of oxidative stress-related diseases such as certain carcinomas. Bioactive compounds represent an alternative to prevent this oxidative-stress. The aim of this study was to elucidate the impact of blood groups on the erythroprotective potential of Fucoxanthin, β-Carotene, gallic acid, quercetin, and ascorbic acid as therapeutic agents against oxidative-stress. The impact of ABO blood groups on the erythroprotective potential was evaluate by the elucidated antioxidant capacity, blood biocompatibility, blood susceptibility and erythroprotective potential (membrane stabilization, in vitro photostability and antihemolytic activity). All antioxidant tested exhibited a highest potent antioxidant capacity and presented the ability to inhibit ROO•-induced oxidative-stress without compromising the cell membrane, providing an erythroprotective effect dependent on the blood group. Effect that increased in the presence of antigen A. This result could be key to the prevention of carcinomas associated with antigen A, such as breast and skin cancer. These results revealed a probable relationship between the different erythrocyte antigens with the erythroprotective potential, highlighting the importance of bio-targeted drugs for groups mostly susceptible to certain chronic-degenerative pathologies. These compounds could be applied as additive, nutraceutical or encapsulated to improve its bioaccessibility.

Whole blood viscosity, a hemorheological factor, is currently used for diagnosis, as it is correlated with various vascular diseases that are difficult to diagnose early with a general blood test. It was determined that it was necessary to set reference intervals for further studies and utilization of whole blood viscosity in cats, a representative companion animal, and this study was conducted. 50 healthy cats were recruited for the study and whole blood viscosity, complete blood count, and serum chemistry tests were performed. The reference intervals of whole blood viscosity were 15.169 to 43.684 cP at a shear rate of 1 s-1 reflecting diastole, and 3.524 to 5.544 cP at a shear rate of 300 s-1 reflecting systole. Red blood cells, hematocrit, hemoglobin, white blood cells, and neutrophils in the complete blood count, and total protein, albumin, globulin, and cholesterol in the serum chemistry were significantly correlated with whole blood viscosity. The results of this study set reference intervals of whole blood viscosity for healthy cats in a wide shear rate range that has not yet been fully established and investigated its correlation with other blood indicators.

This paper presents a study of human blood sera samples, collected in various regions of the Russian Federation, with regard to both vaccine and pandemic avian influenza viral strains. Just before the 2022-2023 epidemic season, herd immunity to seasonal influenza A viruses was reportedly lower than before the COVID-19 pandemic. Since no stable circulation of A/H5Nx and A/H9N2 influenza in the human population was observed during this period, we believe 100% vaccination against seasonal influenza is necessary for employees of poultry farms and other organizations, closely connected to the breeding and processing of poultry. In addition to protection against seasonal influenza, vaccination can hamper the emergence of new viral variants, driven by genome reassortment, during simultaneous infection of humans with seasonal human and animal influenza viruses.

Cytokine adsorption can resolve different complications characteristic of transplantation medicine, such cytokine storm activation, blood immuno- and AB0- incompatibilities but can also be performed for the treatment of various life-threatening conditions, such as sepsis, acute respiratory distress syndrome (ARDS), and cardiogenic shock, all of which can contribute to adverse clinical outcomes during transplantation. After surgery, dysmetabolism and stress response limit successful graft survival and can lead to primary (PGD) or secondary graft dysfunction. In this clinical context, and given that a major problem in transplant medicine is that the demand for organs far exceeds the supply, a technological innovation such as a hemoadsoption system could greatly contribute to increasing the number of usable organ donors. The objectives of this review are to describe the specific advantages and disadvantages of the application of cytokine adsorption in the context of transplantation and also to examine, before and/or after organ transplantation, the benefits of addition of a complementary cytokine adsorption therapy protocol.

Blood biomarkers represent a promising future for studying cognitive impairment, particularly in Alzheimer's Disease (AD), as they offer a non-invasive alternative to cerebrospinal fluid tests and have potential as population screening tools. However, the relationships between these biomarkers and specific cognitive functions, as well as their utility in predicting longitudinal cognitive decline, are not yet fully understood. This descriptive review surveys the literature from 2018 to 2023, focusing on the associations between Amyloid-β, Total Tau, Phosphorylated Tau (p-tau), Neurofilament Light (Nfl), and Glial Fibrillary Acidic Protein (GFAP) with cognition. The reviewed studies are heterogeneous, varying in design and population (mixed, cognitively impaired, or unimpaired), and show results that are sometimes conflicting. Generally, cognition positively correlates with Aβ levels, especially when evaluated through the Aβ42/Aβ40 ratio. In contrast, Tau, Nfl, and GFAP levels typically show a negative correlation with cognitive performance. While p-tau measures tend to show stronger associations with cognitive functions than other biomarkers, no single blood marker has emerged as predominantly associated with a specific cognitive domain. These findings add to our understanding of the complex relationship between blood biomarkers and cognitive performance and underscore their potential utility in clinical evaluations of cognition.

Central Nervous System (CNS) cancers pose a formidable challenge in the medical world, characterized by aggressive behaviors and limited therapeutic options. The emergence of nanomedicine has offered new hope in CNS cancer treatment. The COVID-19 pandemic has further accelerated the need for innovative therapeutic strategies, emphasizing the significance of nanomedicine in this era. This mini review explores the current status of nanomedicine in CNS cancer therapy, with a particular focus on the post-COVID-19 landscape. We discuss the unique challenges presented by CNS cancers, the potential of nanomedicine in overcoming these challenges, and the recent developments in the field. Additionally, we highlight the lessons learned from the pandemic and how they can be applied to improve CNS cancer therapeutics. We also shed light on the evolving regulatory landscape and the prospects of personalized nanomedicine in CNS cancer treatment. The integration of nanomedicine in CNS cancer therapy is becoming increasingly promising, and its role in the post-COVID-19 era is poised to shape the future of neuro-oncology.

Superficial discolored spots on Atlantic salmon (Salmo salar) fillets are a serious quality problem for commercial seafood farming. Previous reports proposed that the black spots (called melanized focal changes (MFC)) may be melanin, but no convincing evidence has been reported. In this study, we performed chemical characterization of MFC, and also of red pigment (called red focal changes (RFC)), of salmon fillets using alkaline hydrogen peroxide oxidation and hydroiodic acid hydrolysis. This revealed that the MFC contain 3,4-dihydroxyphenylalanine (DOPA)-derived eumelanin whereas the RFC only contain trace amounts of eumelanin. Therefore, probably, the black color of MFC can be explained by the presence of eumelanin from accumulated melanomacrophages. For the red pigment, we could not find a significant signature of either eumelanin or pheomelanin, and the red color is probably predominantly hemorrhagic in nature. However, we found that in RFC the level of pigmentation did increase together with some melanogenic metabolites. Comparison with a “mimicking experiment,” in which a mixture of a salmon homogenate + DOPA was oxidized with tyrosinase, suggested that the RFC include conjugations of DOPAquinone and/or DOPAchrome with salmon muscle tissue proteins. In short, the results suggest that melanogenic metabolites in MFC and RFC derive from different chemical pathways, which would agree with the two different colorations deriving from distinct cellular origins, namely melanomacrophages and red blood cells, respectively.

There is no well-defined threshold for intra-operative blood transfusion (BT) in advanced epithelial ovarian cancer (EOC) surgery. We developed a Machine Learning (ML)-driven prediction algorithm to trigger and explain a communication alert for BT based on anticipated peri-operative events irrespective of BT policies. We analysed prospectively collected data from 403 EOC patients who underwent cytoreductive surgery between 2014 and 2019. We calculated the estimated blood volume (EBV) using the formula EBV = weight x 80 and set off 10%EBV as threshold for individual intervention. Based on the known estimated blood loss (EBL) we identified two groups. We employed Receiver operating characteristic (ROC) curves for performance metrics. The model performance for the above threshold prediction was satisfactory (AUC 0.823, 95% CI 0.76-0.88). The top feature commonly shared between interrogators was operative time (OT). Intra-operative blood loss of at least 10%EBV was associated with OT&gt;250 minutes, primary surgery, serous histology, performance status 0, R2 resection and surgical complexity score &gt;4. Large bowel resection, stoma formation, ileocecal resection/right hemicolectomy, mesenteric resection, bladder and upper abdominal peritonectomy were amongst sub-procedures clearly associated with increased intervention risk. Precise prediction of blood requirements is not possible unless a rough estimate of OT is known in advance.

Deep Learning (DL) has made significant advances in computer vision with the advent of Vision Transformers (ViT). Unlike Convolutional Neural Networks (CNNs), ViTs use self-attention to extract both local and global features from image data, and then use residual connections to feed these features directly into a fully networked multilayer perceptron head. In hospitals, hematologists prepare peripheral blood smears (PBSs) and read them under a medical microscope to detect abnormalities in blood counts such as leukemia. However, this task is time-consuming and prone to human error. This study investigates the transfer learning process of Google ViT and ImageNet CNNs to automate the reading of PBSs. The study used two online PBS datasets, PBC and BCCD, and transferred them into balanced datasets to investigate the influence of data amount and noise immunity on both neural networks. The PBC results show that Google ViT is an excellent DL neural solution for data scarcity. The BCCD results show that Google ViT is superior to ImageNet CNNs in dealing with unclean, noisy image data because it is able to extract both global and local features and use residual connections, despite the additional time and computational overhead.

In this work, an entropy-stable and well-balanced numerical scheme for a one-dimensional blood flow model is presented. Such scheme is obtained from an explicit entropy conservative flux along with a second order discretization of the source term by using centered finite differences. We prove that the scheme is entropy-stable and preserves steady-states solutions. In addition, some numerical examples are included to test the performance of the proposed scheme.

Our previous studies showed that in patients with brain diseases neurotrophic factors in lacrimal fluid (LF) may change more prominently than in blood serum (BS). Since glial cell line-derived neurotrophic factor (GDNF) is involved in control of neuronal networks in epileptic brain, we aimed to assess GDNF levels in LF and BS as well as BDNF, hypothalamic-pituitary-adrenocortical and inflammation indices in BS of patients with focal epilepsy (PWFE), epilepsy and comorbid depression (PWFE+MDD) compared with major depressive disorder (PWMDD) and healthy controls (HC). GDNF levels in BS were similar in patients and HC and higher in PWFE taking valproates. GDNF levels in LF were significantly lower in all patient groups compared to controls, and independent of drugs used. LF and BS GDNF concentrations positively correlated in HC, but not patient groups. BDNF level was lower in BS of patients compared with HC and higher in PWFE+MDD taking valproates. Logistic regression models demonstrated that GDNF decrease in LF may be an important predictor of focal epilepsy. Probability of focal epilepsy can be evaluated using GDNF in LF and BDNF in BS; MDD - GDNF in LF, cortisol and TNF-α in BS; epilepsy with MDD - GDNF in LF, TNF-α and BDNF in BS.

Familial Exudative Vitreoretinopathy (FEVR), Norrie disease, and persistent fetal vascular syndrome (PFVS) are extremely rare retinopathies that are clinically distinct but are unified by abnormal retinal endothelial cell function – and subsequent irregular retinal vascular development and/or aberrant inner blood-retinal-barrier (iBRB) function. The early angiogenesis of the retina and its iBRB is a delicate process that is mediated by the canonical Norrin Wnt-signaling pathway in retinal endothelial cells. Pathogenic variants in genes that play key roles within this pathway such as NDP, FZD4, TSPAN12, and LRP5, have been associated with the incidence of these retinal diseases. Recent efforts to further elucidate the etiology of these conditions have not only highlighted their multigenic nature but have also resulted in the discovery of pathological variants in additional genes such as CTNNB1, KIF11, and ZNF408, some of which operate outside of the Norrin Wnt-signaling pathway. Recent discoveries of FEVR-linked variants in two other Catenin genes (CTNND1, CTNNA1) and the Endoplasmic Reticulum Membrane Complex Subunit-1 gene (EMC1) suggest that we will continue to find additional genes that impact the neural retinal vasculature, especially in multi-syndromic conditions. The goals of this review are to briefly highlight the current understanding of the roles of their encoded proteins in retinal endothelial cells to understand the essential functional mechanisms that can be altered to cause these very rare pediatric retinal vascular diseases.

This study aimed to investigate the potential correlations and differences between patients with Acute Coronary Syndrome (ACS) and controls. Emphasis was placed on examining the relationship between arterial blood gas PH value and arterial blood gas lactate value as well as assessing the utility of the Peripheral Perfusion Index (PI) in ACS management. Materials and Methods: A prospective observational study was conducted between January 1, 2023, and July 1, 2023, involving 60 ACS patients and 30 control subjects in an emergency department. The diagnosis of ACS was confirmed by experienced emergency physicians, and various parameters, such as peripheral perfusion index, blood gas values, and cardiac biomarker values, were collected. The statistical analyses included Pearson’s chi-square test, Mann-Whitney U test, Student’s t-test, and others, using SPSS version 18.0. There were significant differences in the mean age, perfusion index, and lactate levels between the patient and control groups. A robust negative correlation was found between age and PI, and a moderate negative correlation was observed between pH and lactate levels (r = -0.301, p=0.004). The perfusion index in the patient group was significantly lower, indicating its potential diagnostic utility. The findings demonstrate the importance of arterial blood gas pH and lactate values in understanding ACS patient profiles, emphasizing the potential of PI as a noninvasive diagnostic method. The negative correlation between pH and lactate levels may offer valuable insights into risk stratification and treatment strategies for patients with ACS.

Studies in the field of experimental hypnosis highlighted the role of hypnotizability in the physiological variability of the general population. It is associated, in fact, with a few differences which are observable in the ordinary state of consciousness and in the absence of suggestions. The aim of the present scoping review is summarizing them, and indicate their relevance to the neural mechanisms of hypnosis and to the prognosis and treatment of a few medical conditions. Individuals with high, medium and low hypnotizability scores display different cerebral functional differences – i.e., functional equivalence between imagery and perception/action, excitability of the motor cortex, interoceptive accuracy - possibly related to brain structural and functional characteristics -, and different control of blood supply at peripheral and cerebral level, likely due to different availability of endothelial nitric oxide. These differences are reviewed to support the idea of their participation in hypnotic behaviour and to indicate their prognostic and therapeutic usefulness in a few medical conditions.

The study aimed to manage and to analyse the results of the laboratory tests, routinallypractice for hepatitis C diagnosis, using blood tests. Statistical analysis of this study results, was performed using the laboratory informatic system. The results of the study are substantial and intricate reffering to comparision between two methods concretlly ELISA method (Enzyme-Linked Immunosorbent Assay) and chemiluminescence methods and their results. Good to know our opinion that RT-PCR technique, it is considered proper for the diagnosis of HCV ( Hepatitis C virus).