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.

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.

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.

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.

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.

The aim of this study was to examine and understand the physiological and biochemical components of the blood and vitreous humor of goldfish (Carassius auratus). Blood was drawn from the arterial (static) line and vitreous humour was extracted using a syringe from healthy goldfish. An automatic haematology analyzer was used to detect 17 physiological indicators, including white blood cells and red blood cells. At the same time, 20 biochemical indexes, including albumin, calcium, and glutamic pyruvic transaminase, were found in the automatic biochemical analyzer. Experiments were also conducted on the effect of blood and vitreous fluid collection on the subsequent survival rate of the celestial goldfish. The findings demonstrated that there were values for 17 physiological indicators in the blood of the goldfish, including red blood cells (2.19 × 1012), white blood cells (62.21 × 109), hemoglobin (138.25g/L), and no eosinophils or basophils. However, no data for 17 physiological indications of vitreous humor were discovered. The quantities of total protein, glutamic oxaloacetic transaminase, and potassium in the vitreous humor were substantially lower than those in the serum (P < 0.01) according to the results of 20 biochemical indexes in the serum and vitreous humor of goldfish. Alkaline phosphatase, chlorine, and creatinine between vitreous humor and serum did not differ significantly(P > 0.05). The levels of glutamic pyruvic transaminase and γ-glutamyl transpeptide in vitreous humor were significantly higher than those in serum (P < 0.01). This experiment provides basic datas for the healthy culture of goldfish and the perfection of hematology in goldfish, and the results will be convenient for the further study of development and formation of celestial eye traits.

The blood-brain barrier (BBB) acts as a specialized structure separating the brain from peripheral blood circulation and plays an important role in brain function. Following an ischaemic stroke or cerebral ischaemia, the BBB is damaged leading to degraded proteins being released into blood circulation. However, little is known about cerebral ischaemia and reperfusion (I/R) induced BBB damage and changes in circulatory biomarkers. This study aims to use both immunohistochemistry and western blotting (WB) to examine neuronal death, glial cell alterations and changes in BBB tight junction (TJ) proteins such as zonula occludens-1 (ZO-1), Occludin and Claudin-5 in the hippocampus in a murine model of cerebral I/R. The changes in these proteins in the blood serum of this model were assessed by enzyme-linked immunosorbent assay. The results showed neuronal death and a significant increase in glial fibrillary acidic protein (GFAP), a protein primarily expressed in astrocytes and a significant decrease in TJ proteins, ZO-1, Occludin and Claudin-5 in the hippocampus of occluded mice as compared to sham-operated mice. These changes are associated with an increased level of these proteins in blood serum in ischaemic mice, suggesting that these proteins can be used as potential biomarkers for determining ischaemic stroke.

This work presented the design and fabrication of blood vessel and breast tumor detection device (BKA-06) based on optical energy spectroscopy. The BKA-06 device uses red-to-near-infrared light-emitting diodes that allow physicians or physicians to visualize blood vessels and surface structures such as breast tumors with the naked eye. The device consisted of built-in current control circuit to have the appropriate brightness (maximum illuminance of 98592 lux) for the examination of superficial tumors deep under the skin, with a scan time of 3-5 minutes. The device BKA-06 could facilely observe each layer of blood vessels at the depth of the skin. For breast tumors, the location, size and invasive areas around the tumor can also be visualized with the naked eye using the BKA-06 sensor. The results show that the BKA-06 sensor can provide clear breast tumor and vascular images with a penetration of up to 15 cm in the skin and tissue layers of the breast. The breast tumor scanning tests with the BKA-06 sensor gave patients quick results and compared them through cell biopsy and MRI respectively. The device has the advantage of being simple, easy to use, providing potential practical applications in the medical field, reducing costs for patients when taking MRI or CT scans. Therefore, the BKA-06 device is expected to help doctors and medical staff overcome difficulties in infusion as well as identify breast tumors to support early breast cancer diagnosis and treatment.

In order to provide a new direction for the diagnosis and treatment of gastric cancer, the differentially expressed blood-based miRNAs in gastric carcinoma were obtained and analyzed from the datasets GSE113486, GSE112264 and GSE113740 by the SangerBox, the miRNA - target genes prediction, GO and KEGG functional enrichment analyses with DAVID 6.8, and the STRING database with Cytoscape, respectively. The correlation between the key miRNAs expression and the prognosis and diagnostic value of gastric cancer patients were detected by survival prognosis and ROC curve. QRT-PCR was used to detect the possible key miRNAs expression in human blood species. The dataset GSE108307 which shows the miRNAs affected by H. pylori infection was analyzed by GEO2R. The expression level of CagA and the clinically used gastric cancer markers were detected in human blood species for contrast. Five key blood-based miRNAs were determined, including hsa-miR-124-3p, hsa-miR-125a-3p, hsa-miR-29b-3p, hsa-miR-4276, and hsa-miR-575.The detection in human blood species as well as the cross analysis with H. pylori infection and clinically used markers expression suggested the importance and efficacy of the specific miRNAs in the early diagnosis and monitoring of gastric carcinoma. The study identified potential novel blood miRNA biomarkers of gastric cancer by bioinformatics and human blood species detection, which may give a new possibility of the important biomarkers for the diagnosis and prognosis of gastric cancer.

(1) Background: The elderly who have chewing difficulty (CD) are prone to malnutrition, frail-ty, and sarcopenia, and those with insufficient physical activity (IPA) are also prone to frailty, overweight, and high blood cholesterol. There is an urgent need to prepare functional foods and to promote healthy physical activity for the elderly over 70 years of age to prevent poor nutri-tion and frailty. (2) Methods: This study prepared functional foods (FF) with softened chicken moose and milkfish without fin for the elderly and compared the different effects of FF from those of music aerobic exercise (MAE) on the complete blood counts, blood biochemistry, in-cluding nutrition index of albumin, and cholesterol levels, and frailty scores before and after in-stitution of FF and MAE among residents of long-term care institutes. (3) Results: The FF signif-icantly increased the high-density lipoprotein cholesterol and albumin levels. In contrast, MAE significantly increased red blood cells (RBC), and decreased the rates of frailty items on fatigue feeling and low physical activity. In comparison between FF and MAE groups, we found that the FF for 5 weeks significantly improved better on HDL-C and MCV while the MAE for 10 weeks improved significantly better on hematopoiesis as increases in red blood cells and platelets. (4) Conclusions: Results from this study suggest that FF and MAE for the elderly have different ef-fects on nutrition status, blood biochemistry and frailty. A combination of both FF and MAE might provide better benefits of nutrition status, physical function, and frailty for the elderly.

Background: The intrauterine and early extrauterine development represents a “window of opportunity” in the immunological development. The underlying mechanisms are still poorly understood. The aim of this study was to provide reference values B cell subpopulations in cord blood of term newborns, juveniles and in adults to find the spectrum of their physiological age-related variation. Methods: In this study, we used flow cytometry to evaluate human B lymphocytes and subpopulations in cord blood (n = 10), in peripheral blood from healthy juveniles aged 1 to 17 years (n=20) and from donors aged 24 to 62 years (n = 10). Results: Our findings showed increasing frequencies of IgM memory B cells, class-switched memory B cells, marginal zone B cells and plasmablasts, from cord blood to peripheral blood of juveniles and adults. In con-trast, the percentage of naïve B cells was higher in newborns than in juveniles and adults. The frequencies of were similar in cord blood and peripheral blood of adults. Interestingly, transitional B cells frequencies were similar in cord blood and adults but significantly lower in juveniles. Conclusions: The frequencies of circulating B cell subpopulation are subject to considerable changes during on-togeny, reflecting overlying effects of maturation and of the acquisition of an adaptive immune memory.

The aim of this study was to verify the effects of blood flow restriction on movement velocity and muscle activity during the back-squat exercise. Methods: Twenty-four university students participated in this study. In two randomized 72-hours apart sessions, participants performed a 4-set protocol consisting of 30-15-15-15 repetitions performed at 30% of their one-repetition maximum in the back-squat exercise. In both sessions, neuromuscular function was monitored by surface electromyography (EMG) and movement velocity (mean propulsive velocity [MPV], peak concentric velocity [Vmax] and the effort index [EI]). Blood flow restriction (BFR) was applied during exercise in one of the experimental sessions with 80% of full arterial occlusion pressure over lower limbs. Results: BFR condition showed higher (p&lt;0.05) EI, peak and rooted mean square normalized EMG in set 1 compared to set 2. Similar MPV and Vmax were observed at each set for both BFR and control conditions. No significant differences were observed between conditions at any set. Conclusions: BFR did not imply changes in neuromuscular performance during low-intensity resistance training, but it might induce greater intra-series velocity loss and less activation of the muscles involved.

Hemorrhage is a detrimental event present in traumatic injury, surgery, and disorders of bleeding, that can become life-threatening if not properly managed. Moreover, uncontrolled bleeding can complicate surgical interventions, altering the outcome of surgical procedures. Therefore, to reduce the risk of complications and decrease the risk of morbidity and mortality associated with hemorrhage, it is necessary to use an effective hemostatic agent that ensures immediate control of bleeding. In recent years, there have been increasingly rapid advances in developing novel generation of biomaterials with hemostatic properties. Nowadays, a wide array of topical hemostatic agents is available, including chitosan-based biomaterials that have shown outstanding properties such as: antibacterial, antifungal, hemostatic, analgesic activity, in addition to their biocompatibility, biodegradability, and wound-healing effects. This review provides an analysis of chitosan-based hemostatic and discusses the progress made in their performance, mechanism of action, efficacy, cost, and safety in recent years.

Chia seed, high in dietary-fiber and protein, may have potential to increase satiety. However, previous studies are confounded by differences in energy intake, and none investigated doses &lt;7g. We compared the subjective appetite and glycaemic responses elicited by 30g cookies containing 0, 3, 5 or 7g chia seed (CS0, CS3, CS5 or CS7, respectively, 140-150kcal, 7-8g fat, 4g protein, 0-2g dietary-fiber, 16g available-carbohydrate) using a randomized, double-blind, cross-over design. Overnight-fasted heathy adults (24 males, 22 females; mean±SD age 37±13y; BMI 27.4±3.9kg/m²) consumed test-cookies and had appetite and plasma-glucose measured before and intermittently for 3h after eating. Data were analyzed by ANOVA with Tukey’s test to adjust for multiple comparisons; the criterion for significance was 2-tailed p&lt;0.025 for the primary endpoints of total area under the curve (tAUC0-3h) for hunger and fullness. Hunger tAUC0-3h was similar among treatments (p=0.49) but fullness differed (p=0.019) with tAUC0-3h after CS3&gt;CS7 (mean±SEM) (140±9 vs 122±10mm×h, p&lt;0.025). Mean incremental glucose AUC0-2h after CS3, CS5 and CS7, respectively, were 22%, 23% and 30% less than CS0 (p&lt;0.05). Thus, although chia reduced glycemic responses, we were unable to demonstrate a significant effect of ≤7g chia seed on the primary endpoints of hunger or fullness tAUC0-3h versus control.

The Neurovascular Unit (NVU), comprised of glia (astrocytes, oligodendrocytes, microglia), neurons, pericytes and endothelial cells, is a dynamic interface ensuring physiological functioning of the central nervous system (CNS), that gets affected and contributes to the pathology of several neurodegenerative diseases. Neuroinflammation is a common feature of neurodegenerative diseases and is primarily related to the activation state of perivascular microglia and astrocytes, which constitute two of its major cellular components. Our studies focus on monitoring in real time the morphological changes of perivascular astrocytes and microglia, as well as their dynamic interactions with the brain vasculature, under physiological conditions and following systemic neuroinflammation triggering both microgliosis and astrogliosis. To this end, we performed 2-photon laser scanning microscopy (2P-LSM) for intravital imaging of the cortex of transgenic mice visualizing the dynamics of microglia and astroglia following neuroinflammation induced by systemic administration of the endotoxin lipopolysaccharide (LPS). Our results indicate that following neuroinflammation the end-feet of activated perivascular astrocytes lose their close proximity and physiological crosstalk with vasculature, an event that most possibly contributes to a loss of blood-brain-barrier (BBB) integrity. At the same time, microglial cells get activated with more frequent contacts of the blood vessels. These dynamic responses of perivascular astrocytes and microglial are peaking at 4 days following LPS administration, however they still persist at a lower level 8 days after LPS, revealing incomplete reversal of inflammation affecting the glial properties and interactions with the NVU.

In a completely randomized design (CRD), 400 day-old Ross 308 broilers were randomly allotted to 5 diets with 0, 5, 10, 15 and 20% MSC, each with 8 replicates of 10. Weekly feed intake (FI), body weight gain (BWG) and feed conversion efficiency (FCE) were calculated whilst haemato-biochemistry was measured at d42. Overall, FI was linearly (P &lt; 0.05) and quadratically (P &lt; 0.01) decreased by MSC, of which the optimum inclusion was 15%, as BWG was linearly (P &lt; 0.001) and quadratically (P &lt; 0.05) decreased and FCE linearly decreased (P &lt; 0.01) by MSC, of which the optimum dietary inclusion was 10%. Also, MSC linearly and quadratically decreased slaughter weight (P &lt; 0.001 and P &lt; 0.05, respectively), hot carcass weight (P &lt; 0.001 and P &lt; 0.05, respectively) and cold carcass weight (P &lt; 0.001 and P &lt; 0.05, respectively). Similarly, it linearly decreased white blood cells (P &lt; 0.01) and lymphocytes (P &lt; 0.05) as it linearly (P &lt; 0.001) and quadratically (P &lt; 0.01) decreased symmetric dimethylarginine (SDMA) and linearly (P &lt; 0.001) increased serum cholesterol. In conclusion, up to 10% MSC can be incorporated into broiler diets in replacement of SBM without adverse effects.

To investigate the impacts of various sources of omega-3 on feed intake, digestibility, and blood metabolites in horses, this research was conducted. In this survey, 6 medium-sized Turkmen horses, aged 14 to 16 years, were used. The horses had no movement and health problems. This research was carried out in the form of a rotating design and included 3 periods, and each treatment had 2 repetitions in each period. In each experimental period, horses were randomly assigned to each of the 3 experimental treatments. The experimental treatments included C) Omega-3-free supplement (control treatment), R) Persialin flaxseed oil, and P) Persialin fat powder. At the beginning of each period, after the withdrawal period for the previous period, blood and feces samples were taken as the covariate factors, then the experimental treatments were consumed for 14 days, and after the adaptation to 100 grams of supplementing fat powder or flax seed oil, blood, and feces samples were taken at the end of the course. Fat supplements were added to the concentrate 1.5 hours before feeding the midday hay. The palatability was affected by the P treatment and was significantly lower than the R and C groups (P<0.05). But the difference between the two treatments (R and C) was insignificant in any of the periods. The digestibility of acid detergent insoluble fiber (ADF), crude protein (CP), ether extract (EE), and organic matter were not affected by any of the experimental treatments. Blood metabolites including glucose, cholesterol, triglyceride, total protein, and blood urea nitrogen were not influenced by experimental treatments. The serum albumin concentration of horses was affected by the R treatment in the first and third periods, but no significant difference was observed between the treatments in the second period.

The blood-brain barrier (BBB) is a selectively permeable boundary that separates the circulating blood from the extracellular fluid of the brain and is an essential component for brain homeostasis. In glioblastoma (GBM), the BBB of peritumoral vessels is often disrupted. Pericytes, being important to maintain the BBB integrity, can be functionally modified by GBM cells by inducing proliferation and cell motility via the TGF-β-mediated induction of central epithelial to mesenchymal transition (EMT) factors., We demonstrate that pericytes strengthen the integrity of the BBB in primary endothelial cell/pericyte co-cultures as in vitro BBB model, using TEER measurement of the barrier integrity. In contrast, this effect was abrogated by TGF-β or conditioned medium from TGF-β secreting GBM cells, finally leading to the disruption of a so far intact and tight BBB. TGF-β dramatically changed the metabolic behavior of pericytes, such as shutting down the TCA cycle, driving energy generation from oxidative phosphorylation towards glycolysis, and by shifting the cells towards the activation of pathways that are necessary to produce molecules used for proliferation and cell division. Furthermore, combined metabolomics and RNASeq analyses indicated that the observed functional changes of TGF-β-treated pericytes are closely connected with their behavior.

Magnetic Nanoparticles (MNPs) is a promising technique to cure brain diseases. On the one hand, by serving as drug carriers, they can bypass the blood-brain barrier and deliver drug molecules to the brain parenchyma; on the other hand, their transport trajectory can be manipulated by applying an external magnetic field. However, due to the complex microstructure of brain tissues, e.g. the anisotropy of white matter (WM), how to achieve desired drug distribution patterns, e.g. uniform distribution, by tuning the drug delivery system is largely unknown. Here, in this study, by adopting a mathematical model capable of capturing the diffusion trajectories of MNPs in the microstructures, we systematically investigated the effects of key parameters in the MNPs delivery system on the equivalent diffusion coefficient of MNPs in the microenvironment of brain WM. The results show that uniform distribution of MNPs in anisotropic tissues can be achieved by adjusting the particle size and magnetic field. We have not only obtained a deeper understanding on how to optimise the MNPs delivery system, it can also be anticipated that an improved mathematical model could even help to achieve complex drug distribution patterns in the complicated brain environment by designing an appropriate combination of the key parameters.

(1) Background: High blood pressure is one of the symptoms of stroke, the Self Care Deficit theory by Dorothea Orem focuses on a person's ability to care for himself independently so that the ability to maintain his health and well-being is achieved. There are currently 600 million hypertensive patients worldwide, of which 3 million die every year. Uncontrolled high blood pressure can lead to a 7-fold increase in the chances of stroke. The existence of this condition can be minimized in patients through several innovative interventions, one of which is foot massage. This study aims to determine the effectiveness of stretching and foot massage with lavender oil in stabilizing high blood pressure in stroke patients.(2) Methods: The method used in this research is descriptive. The subjects of this case study were selected according to the inclusion and exclusion criteria of the journal Evidence-Based. Subjects included intervention patients and control patients. Foot massage therapy with lavender oil is done 2 times a day for 10-15 minutes using the effleurage technique after showering in the morning and evening. Stretching is done 2 times a day every 10-15 minutes.(3) Results: The results of the analysis showed that there was a change in blood pressure after the application of stretching and foot massage with lavender oil. From the initial examination, the results showed that the blood pressure of 170/100 mmHg decreased to 140/90 mmHg and the pain scale decreased from 4 to 0.

Worldwide, it is estimated that at least 1 in 4 adults suffers from hypertension, and this number is expected to increase as populations grow and age. Blood pressure (BP) possesses substantial heritability, but is also heavily modulated by lifestyle factors. As such, digital, lifestyle-based in-terventions are a promising alternative to standard care for hypertension prevention and man-agement. In this study we assessed the prevalence of elevated and high BP in a Dutch general pop-ulation cohort undergoing a health screening, and observed the effects of a subsequent self-initiated, digitally-enabled lifestyle program on BP regulation. Baseline data were available for 348 participants, of which 56 had partaken in a BP-focused lifestyle program and got re-measured 10 months after the intervention. Participants with elevated SBP and DBP at baseline showed a mean decrease of 7.2 mmHg and 5.4 mmHg, respectively. Additionally, 70% and 72.5% of participants showed an improvement in systolic and diastolic BP at remeasurement. These improvements in BP are superior to those seen in other recent studies. The long-term sustainability and the efficacy of this and similar digital lifestyle interventions will need to be estab-lished in additional, larger studies.

Introduction: multiple sclerosis (MS) is the most common immune-mediated chronic neurodegenerative disease of the central nervous system (CNS), affecting young people. Due to the permanent disability, cognitive impairment, and the enormous detrimental impact MS can exert on the patients’ health-related quality of life. It is of great importance to recognise it in time and commence adequate treatment at an early stage. The currently used disease-modifying therapies (DMT) aim to reduce disease activity and thus halt disability development, which in current clinical practice are monitored by clinical and imaging parameters but not by biomarkers found in blood and/or the cerebrospinal fluid (CSF). Both clinical and radiological measures routinely used to monitor disease activity lack information on the fundamental pathophysiological features and mechanisms of MS. Furthermore, they lag behind the disease process itself. By the time a clinical relapse becomes evident or a new lesion appears on the MRI scan, potentially irreversible damage has already occurred in the CNS. In recent years several biomarkers that previously have been linked to other neurological and immunological diseases have received increased attention in MS. Additionally, other novel, potential biomarkers with prognostic and diagnostic properties have been detected in the CSF and blood of MS patients. Areas covered: in this review, we summarise the most up to date knowledge and research conducted on the already known and most promising new biomarker candidates found in the CSF and blood of MS patients. Author commentary: the current diagnostic criteria of MS rely on three pillars; MRI imaging, clinical events and the presence of oligoclonal bands in the CSF (which was reinstated into the diagnostic criteria by the most recent revision). Even though the most recent McDonald criteria made the diagnosis of MS faster than the prior iteration, it is still not an infallible diagnostic toolset, especially at the very early stage of clinically isolated syndrome. Together with the gold standard MRI and clinical measures, ancillary blood and CSF biomarkers may not just improve diagnostic accuracy and speed but very well may become agents to monitor therapeutic efficacy and make even more personalised treatment in MS a reality in the near future. The major disadvantage of these biomarkers in the past has been the need to obtain CSF to measure them. However, the recent advances in extremely sensitive immunoassays made their measurement possible from peripheral blood even when present only in minuscule concentrations. This should mark the beginning of a new biomarker research and utilisation era in MS.

Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with a significantly increased risk of cardiovascular mortality, mainly attributed to accelerated atherosclerosis. Methods: Thirty-two women (aged more than 18 years) with RA, and 25 age-matched healthy women were included in this study. Biomarkers of inflammation, red blood cells (RBCs) redox balance, estrogen receptor alpha (ER-α) expression as well as ERK 1/2 phosphorylation content were evaluated in RA patients at baseline and six months after treatment with disease modifying anti‐rheumatic drugs (DMARDs). Results: For the first times we demonstrated that in RA patients: i) disease activity score (DAS-28) positively correlated with RBC ER-α expression, and negatively with total antioxidant capacity of plasma; ii) RBC ER-α expression positively correlated with systemic inflammatory biomarkers and oxidative stress parameters as well as ERK 1/2 phosphorylation; and iii) DMARDs treatments improved the clinical condition measured by DAS-28 score decrease, although the RBCs appeared to be more prone to pro-oxidant status associated to the expression of survival molecules. Conclusion: Our data strongly suggest that RBCs could also participate in vascular homeostasis through fine modulation of an intracellular signal linked to the ER-α.

Glioblastoma is one of the most difficult tumor types to treat with conventional therapy options like tumor debulking, chemo and radiotherapy. Immunotherapeutic agents like oncolytic viruses, immune checkpoint inhibitors and chimeric antigen receptor T cells have revolutionized cancer therapy, but their success in glioblastoma remains limited and further optimization of immunotherapies is needed. Several oncolytic viruses have demonstrated ability to infect tumors and trigger anti-tumor immune responses in malignant glioma patients. Leading the pack, oncolytic herpesvirus, first in its class, awaits an approval for treating malignant glioma from MHLW, the federal authority of Japan. Nevertheless, some major hurdles like the blood brain barrier, immunosuppressive tumor microenvironment, and tumor heterogeneity can engender suboptimal efficacy in malignant glioma. In this review, we discuss the current status of malignant glioma therapies with a focus on oncolytic viruses in clinical trials. Furthermore, we discuss the obstacles faced by oncolytic viruses in malignant glioma patients and strategies that are being used to overcome these limitations to 1) optimize delivery of oncolytic viruses beyond the blood brain barrier; 2) trigger inflammatory immune responses in and around tumors; and 3) use of multimodal therapies in combination to tackle tumor heterogeneity, with an end goal of optimizing the therapeutic outcome of oncolytic virotherapy.

Sickle cell disease (SCD) is the most common hereditary disorder of hemoglobin (Hb) that affects approximately a millions people worldwide. It is characterized by a single nucleotide substitution on the β-globin gene, leading to the production of abnormal sickle hemoglobin with multi-system consequences. Mutated Hb leads to profound changes in: i) red blood cell metabolism and physiology; ii) endothelial signaling; and iii) immune response. Oxidative stress is an important hallmark of SCD. It plays a key role in the pathophysiology of hemolysis, vessel occlusion and the following organ damage in sickle cell patients. For this reason, reactive oxidizing species and the (end)-products of their oxidative reactions have been proposed as markers of both tissue pro-oxidant status and disease severity. Although more studies are needed to clarify their role, antioxidant agents have been shown to be effective in reducing pathological consequences of the disease by preventing oxidative damage in SCD, i.e. by decreasing the oxidant formation or repairing the induced damage. An improved understanding of oxidative stress will lead to targeted antioxidant therapies that should prevent or delay the development of organ complications in this patient population.

Peripheral blood is an available source of adult stem cells for both fundamental research and clinical use. Peripheral blood mononuclear cells (PBMCs) contain a number of different multipotent populations of progenitor cells and possess a potential to differentiate into various types of cells under appropriate conditions. We have evaluated a regenerative potential of PBMCs embedded into fibrin matrix (FM) in a model of pig spinal cord injury. The distribution of transplanted PBMCs in the injured spinal cord was previously evaluated, which demonstrated the ability of these cells to penetrate into deep layers of the spinal cord and to concentrate mainly in the grey matter. The pilot study conducted demonstrated that the tissue structure could be improved and the conduction along posterior columns of the spinal cord could be partially recovered in animals in the setting of FM+РВМCs application. The multiplex analysis of blood serum and cerebrospinal fluid (CSF) showed the cytokine imbalance to occur without significantly shifting towards pro-inflammatory or anti-inflammatory cytokine cascades in the setting therapy provided.

Inherited platelet disorders (IPDs) are rare diseases featured by low platelet count and/or defective platelet function. Patients have variable bleeding diathesis and sometimes additional features that can be congenital or acquired. Identification of an IPD is desirable to avoid misdiagnosis of immune thrombocytopenia and use of improper treatments. Diagnostic tools include platelet function studies and genetic testing. The latter can be challenging as the correlation of its outcomes with phenotype is not easy. The immune-morphological evaluation of blood smear (by light- and immunofluorescence microscopy) represents a reliable method to phenotype subjects with suspected IPD. It is relatively cheap, not excessively time-consuming, and applicable to shipped samples. In some forms, it can provide diagnosis by itself, as for MYH9-RD, or in addition to other first-line tests as aggregometry or flow cytometry. In regard to genetic testing, it can guide specific sequencing. Since only minimal amounts of blood are needed for preparation of blood smears, it can be used to further characterize thrombocytopenia in pediatric patients and even newborns. In principle it is based on visualizing alterations in the distribution of proteins, which result from specific genetic mutations, by using monoclonal antibodies. It can be applied to identify deficiencies in membrane proteins, disturbed distribution of cytoskeletal proteins, and alpha as well as delta granules. On the other hand mutations associated with impaired signal transduction are difficult to identify by immunofluorescence of blood smears. This review summarizes technical aspects and the main diagnostic patterns achievable by this method.

Background: Transit-time flow measurement (TTFM) is frequently used to evaluate intraoperative quality control during coronary artery bypass grafting (CABG). Although TTFM has the ability to assess graft failure intraoperatively, the perioperative factors affecting TTFM during CABG surgery remain poorly understood. Methods: Patients who underwent CABG surgery at a single institution between July 2016 and May 2018 were prospectively evaluated. Patients’ demographic characteristics, previous medical history, Euroscore, the results of preoperative blood tests, and intraoperative data were recorded. TTFM and blood viscosity were measured hemodynamically, and mean flow (mL/min) and pulsatility index (PI) were recorded. Arterial blood gas was analyzed immediately after anastomosis of the left internal mammary artery (LIMA) to the left descending artery (LAD) and before sternal closure. Factors associated with TTFM were assessed by multiple linear regression analysis. Results: Of the 62 patients who underwent CABG surgery during the study period, 57 were evaluated, including 49 who underwent off-pump and eight who underwent on-pump surgery. Blood viscosity was not significantly associated with TTFM (p > 0.05). However, TTFM was significantly associated with body mass index (BMI), systolic blood pressure, and cardiac index (p < 0.05 each). Conclusions: Blood viscosity was not significantly associated with intraoperative graft flow. Blood flow of graft vessels, however, was significantly associated with BMI, systolic blood pressure, and cardiac index.

Background: Sex differences in blood pressure (BP) exist during all reproductive life between women and men whereas a sharper increase in BP occurs after menopause which is associated with increased prevalence of cardiovascular diseases. This study examined cardiovascular and biochemical parameters in perimenopausal women (PW) aiming to investigate the influence of sex on a) office BP and for 24 hours; b) cardiac autonomic modulation; c) redox state by measuring MDA, SOD, and catalase; d) NO_x^- concentration. In addition, aerobic exercise training (AET) was applied for detecting changes in cardiovascular responsiveness during the menopausal transition. Methods: Thirty-one participants were enrolled, healthy PW and age-matched men. Cardiovascular and biochemical biomarkers were evaluated at baseline and after AET (8 weeks of exercise on a treadmill, three sessions/week, duration of 30-40 minutes). Results: At rest, PW presented: a) a lower diastolic BP during daytime; b) a lower absolute and normalized LF component as well as a higher HF normalized component; d) no sex differences for redox biomarkers and NO_x^- concentration. After AET, only PW was responsive in lowering systolic BP that was accompanied by an increase in NO_x^- concentration and SOD activity. Regarding HRV, both groups were responsive to the AET. Conclusions: During the menopausal transition, systolic BP was similar to men whereas cardiac autonomic modulation remained unaltered showing the influence of sex steroids on BP. In Addition, AET was fundamental during the menopause transition by preventing an elevation in BP, minimizing the effects of aging associated with estrogen deficiency on women's cardiovascular health.

The aim of this study is to provide the scientists with a straightforward correlation that can be applied for predicting the Fanning friction factor and consequently the pressure drop during blood flow in small caliber vessels. Due to the small diameter of the conduit, the Reynolds numbers are low and thus the flow is laminar. The study has been conducted using CFD simulations validated with relevant experimental data acquired using an appropriate experimental set-up. The experiments concern pressure drop measurement during the flow of a blood analogue that follows the Casson model, i.e. an aqueous glycerol solution that contains a small amount of xanthan gum and exhibits similar behavior to blood, in a smooth, stainless steel microtube (L=5.6cm and D=400 μm). The interpretation of the resulting numerical data led to the proposal of a simplified model that incorporates the effect of the flow rate, the hematocrit value (35-55%) and the vessel diameter (300-1800 μm) and predicts with better than ±10% the Fanning friction factor and consequently the pressure drop during laminar blood flow in small caliber vessels.

This paper investigates existing mathematical morphology based techniques applied for performing malaria parasites detection and identification in both Giemsa and Leishman stained blood smears images. Malaria is an epidemic health disease and a rapid, accurate diagnosis is necessary for proper intervention. Generally, pathologists visually examine blood stained slides for malaria diagnosis; this kind of visual inspection is subjective, errorprone and time consuming. In order to cope with such issues, computer-aided methods have been increasingly evolved for abnormal erythrocyte and/or parasites detection, segmentation and semi/fully automated classification. The aim of this paper is to present a review of recent mathematical morphology based methods for malaria parasite detection.

Background: Nowadays vital signs in clinics are electronically monitored excepted for urine output which still requires, manual recording, which is subject to human errors. We, in-vitro, assessed in this study the ability a novel electronic device to measure by a combination of two different methods, the real time flow-output, like urine output. Methods: Flow or urine output was measured by a combination technique of gravimetry using a dynamometer and capacitive sensing to improve precision. Data were obtained in 3 different situations, low, medium, and high flow. Results: Three different situations were tested: full or empty dead space and Pasteur’s chamber. The differences between the injected and measured volume varies from 0 to 5 ml representing a maximal error of 3 % regardless of the volume injected and the flow in ml/hour. The capacitive sensors behave as expected with a parallel curve of the expected and measured flow. Conclusion: We have shown in this in-vitro study that the combination of gravimetry and capacitive sensors analysis allow accurate measurement of volume and flow-output. Clinical trials should be conducted to confirm its usefulness in urine output measurement in the real life.

Molluscs are significant species in aquatic ecology. Molluscs are crucial for maintaining ecological balance as secondary consumers and serving as bioindicator species in biomonitoring systems. Molluscs are threatened by pesticides such as commonly used pyrethroid insecticides. Pyrethroids are typical insecticides used to control insects in agriculture and gardening. Pyrethroids are increasingly being utilized in both agricultural and human activities. Pyrethroids enter aquatic bodies through rainfall and drainage systems. The use of pyrethroids is becoming a significant concern for aquatic creatures, particularly molluscs. The discussion will focus on the increasing issue of pyrethroids becoming a nightmare for molluscs. Pyrethroids, due to their lipophilic nature, pose a significant risk to molluscs by affecting their metabolites, producing reactive oxygen species, and influencing neurotransmitter actions. Molluscs are crucial organisms in aquatic ecosystems, and their threats warrant significant discussion and attention. This review will delve into the behaviour of pyrethroids on molluscs.

Soil moisture can be an important indicator of climate change in humid and semi-arid areas. This indicator can more efficiently propose different public policies related to climate change than just using precipitation and temperature data. Given the above, the objective of this study is to evaluate changes in soil moisture in the state of Pernambuco during the period 1961-2021, using the System of Hydrological Response Units for Pernambuco. In this study, two river basins in the state of Pernambuco that represent the different climatic conditions of the state will be chosen. The results show that in the coastal region, there is a tendency towards more saturated soils, and in the semi-arid region, there is a tendency towards drier soils. With these results, it is possible to conclude that public policy decisions for the economy, environment, and society must consider this vital water balance variable.

In cutting processes tool condition affects the quality of the manufactured parts. As such an essential component to prevent unplanned downtime and to assure machining quality is having information about the state of the cutting tool. The primary function of it is to alert the operator that the tool has reached or is reaching a level of ware beyond which behavior is unreliable. In this paper the tool condition is being monitored by analyzing the electric current on the main spindle via an artificial intelligence model utilizing a LSTM neural network. In the current study the tool is monitored while working on a cylindrical raw piece made of AA6013 aluminum alloy with a custom polycrystalline diamond tool, for the purposes of monitoring the ware of these tools. Spindle current characteristics were obtained using external measuring equipment to not influence the operation of the machine included in a larger production line. As a novel approach, an artificial intelligence model based on a LSTM neural network is utilized for the analysis of the spindle current obtained during a manufacturing cycle and assessing the tool ware range in real time. The neural network was designed and trained to notice significant char-acteristics of the captured current signal. The conducted research serves as a proof of concept for use of a LSTM neural network-based model as a method of monitoring the condition of cutting tools.

The research aimed at the ecological assessment of the environment around uranium mining enterprises in the Turkestan region. The authors examined the state of the soil and vegetation for 2021-2023, their chemical composition and the effects of radiation. Excesses of background radiation were detected by alpha and beta studies. To study the structural organization of plant communities, we conducted floristic studies in the areas immediately adjacent to NAC “Kazatomprom” enterprises. The general habitus, size, number and shape of vegetative parts of plants were taken into account as comparison parameters. The flora growing in the study areas of the Suzak district of the region, which is distinguished by its uniqueness and narrow relevance to the ecological conditions of the area, was taken as biological objects of study. To determine the ecological state of the adjacent territories of NAC “Kazatomprom” and for physical, chemical and taxonomic analyses, 78 soil samples and 37 plant samples were obtained. The studied samples were taken near settlements N, B and S, which are closest to the territories of NAC “Kazatomprom”.

Respiratory allergic diseases, affect over 500 million people globally and pose a substantial burden in terms of morbidity, mortality, and healthcare costs. Restrictive factors such as geographical disparities, infectious pandemics, limitations in resource, and shortage of allergy specialists in underserved areas, impede effective management. Moreover, the well-established suboptimal adherence in patients with respiratory allergies, contribute further to the accelerated loss of disease control. Telemedicine encompasses real-time visits, store-and-forward options triage, and computer-based technologies for establishing and efficient doctor-patient communication. Recent advances in digital technology, including designated applications, informative materials, digital examination devices, wearables, digital inhalers, and integrated platforms, facilitate personalized and evidence-based care delivery. The integration of telemonitoring in respiratory allergy care has shown beneficial effects in disease control, adherence, and quality of life. While the COVID-19 pandemic accelerated the adoption of telemedicine, certain concerns regarding technical requirements, platform quality, safety, reimbursement, and regulatory considerations remain unresolved. Challenges in telemonitoring implementation further include ensuring effective doctor-patient collaboration, addressing privacy concerns, and establishing cost-effective models. The integration of artificial intelligence (AI) in telemonitoring applications holds promise for data analysis, pattern recognition, and personalized treatment plans. Striking the balance between AI-enabled insights and human expertise is crucial for optimizing the benefits of telemonitoring. This overview reports the up- to- date telemedicine approaches in managing patients with respiratory allergies. While telemonitoring exhibits potential in enhancing patient care and healthcare delivery, critical considerations have to be addressed in order to ensure the successful integration of telemonitoring into the healthcare landscape.

A temporary monitoring system was installed on the 175-years-old historical Széchenyi chain bridge under its reconstruction process. The bridge is in the downtown area of the capital city of Hungary and plays a significant role in city life of Budapest. Six-month-long measurements were conducted during the reconstruction process of the bridge, yielding crucial insights into the structural behaviour of the historical structure. Measurement results were evaluated; the findings encompass the rotation capacity of pins between chain elements, and structural response to temperature changes. This information helped the decision-making of designers and construction company during the reconstruction made between 2021 and 2023. For instance, daily temperature fluctuations result in increased bending moments in the chain elements, rising up to 158% compared to the values observed during a proof load test in 2018. Furthermore, the measurements reveal an approximate 42% increase in normal forces compared to the proof load test, which highlights the high sensitivity of chain bridges to temperature fluctuations, where geometric stiffness plays a crucial role. Reconstruction, reducing self-weight, notably intensifies the impact on normal forces and bending moments. These outcomes strongly emphasize the dominance of dead load and self-weight in the case of chain bridges.

Road pavement monitoring represents the baseline to the pavement maintenance process. To quickly fix a damaged road, relevant authorities need a high-efficiency methodology that allows them to obtain data describing the current conditions of a network of roads. In urban areas, large-scale monitoring campaigns may be more expensive and not fast enough to describe how pavement degradation has evolved over time. Furthermore, at low speeds, many technologies are inadequate for monitoring the streets. In such a context, employing black box equipped vehicles to perform a routine inspection could be an excellent starting point. However, the vibration-based methodologies used to detect road anomalies are strongly affected by the speed of these vehicles. In this study, a statistical method was to analyze the effects of speed on road pavement conditions at different severity levels through the data recorded by taxi vehicles. Likewise introduced was a process that overcomes the speed effect when considering road surface conditions. The methodology proposed has succeeded in predicting the right damage severity level based on only two recorded parameters: speed and pavement deterioration index.

This observational pilot study aimed to investigate continuous glucose monitoring (CGM) metrics in older Japanese patients with type 2 diabetes mellitus (T2DM) using a continuous glucose monitoring system (FreeStyle Libre Pro) for CGM during the first tirzepatide administration and compared the glycemic control measures before and after the treatment. The four patients re-ported a mean age of 79.5 years (standard deviation [SD]: 5.8), mean body mass index of 24.63 kg/m2 (SD: 4.7), and mean glycated hemoglobin level of 9.1% (SD: 2.1). After tirzepatide treatment, the mean of time in range, time above range, and time below range changed from 53.2% to 78.9% (p = 0.041), 45.8% to 19.7% (p = 0.038), and 1.0% to 1.5% (p = 0.206), respectively. Improved hy-perglycemia reduced the oral glucose medication in two cases and decreased the frequency of insulin injections in two cases. All cases demonstrated the CGM index improvement during short-term observation despite some differences. Future studies need to investigate the long-term impact on functional prognosis, safety, and tolerability, especially in nonobese older Asian pa-tients, to elucidate the potential benefits of tirzepatide. However, tirzepatide-associated robust glycemic improvement may simplify and reduce diabetes treatment-associated complication in older patients with T2DM.

The previous studies on the diversion pipe of pumped storage power stations (PSPS) primarily focused on numerical simulations of pulsating pressure propagation within the pipe and its inducing factors. However, there was a lack of field monitoring and analysis of measured data to support surface ambient vibration, resulting in insufficient credibility and practicality of the numerical results. Based on ambient monitoring and data analysis, this paper examines the factors contributing to the ambient vibration of the water diversion pipeline in Changlongshan (CLS) PSPS. It is concluded that: (1) The primary source of vibration originates from units operation-induced ambient vibrations; (2) Vibration during pumping conditions exceeds that during power generation conditions; (3) The ground measuring point's vibration acceleration primarily depends on the distance from the vibration source; (4) Different types of units have varying effects on water diversion pipeline vibrations.

The Internet of Things (IoT) is experiencing exponential growth, revolutionizing various industries with its ability to connect devices and enable advanced applications. In the realm of energy production, IoT offers significant potential for optimizing processes and improving efficiency. This study presents a comprehensive monitoring and energy management strategy for the University of Cuenca's microgrid photovoltaic (PV) system, utilizing IoT and ThingSpeak as key technologies. The proposed strategy leverages intelligent environments and utilizes ThingSpeak as a robust platform for data presentation and analysis. By integrating IoT devices and sensors, real-time monitoring of PV system parameters such as solar radiation and temperature is achieved. The collected data is then analyzed using advanced algorithms and visualized through ThingSpeak, enabling effective energy management and decision-making. The developed monitoring system was rigorously tested in a laboratory microgrid setting, where the PV system is interconnected with other generation and storage systems, as well as the electrical grid. Through the seamless integration of these components, the monitoring system provides enhanced visibility and control over the microgrid's energy production. The results demonstrate the successful implementation of the monitoring system, showcasing its ability to improve the supervision, automation, and analysis of daily energy production. By leveraging IoT technologies and ThingSpeak, stakeholders can access real-time data, analyze performance trends, and optimize energy resources.

Influenced by geological, climatic, and natural weathering factors, the Great Wall heritage is sus-ceptible to deformations, posing significant challenges to the comprehensive preservation of the Great Wall sites. To investigate techniques for monitoring deformations in extensive linear cultural heritage sites, such as the Great Wall, this study utilizes the SBAS-InSAR technique for deformation monitoring and analysis. A dataset comprising 161 Sentinel-1A images spanning from March 2017 to January 2022 was chosen for SBAS-InSAR processing, yielding a deformation velocity field. To verify result credibility, a typical mountainous segment spanning approximately 896.53 km within the Great Wall landscape corridor underwent analysis. The findings suggest that around 75.8% of the landscape corridor along the Shanxi section of the Ming Great Wall maintain relative stability, displaying deformation rates varying from -10 to 10 mm/year. The remaining 24.2% of the land-scape corridor experiences notable deformations, including a maximum subsidence rate of 33.1 mm/year and a maximum subsidence of 148.6 mm. This study illustrates the potential utility of the SBAS-InSAR technique for monitoring and evaluating surface deformations in extensive linear cultural heritage sites.

Effective management of retinoblastoma (RB), the most prevalent childhood eye cancer, depends on reliable monitoring and diagnosis. A promising candidate in this context is the secreted trefoil family factor peptide 1 (TFF1), recently discovered as a promising new biomarker in patients with a more advanced subtype of retinoblastoma. The present study investigated TFF1 expression within aqueous humor (AH) of enucleated eyes and compared TFF1 levels in AH and corresponding blood serum samples from RB patients undergoing intravitreal chemotherapy (IVC). TFF1 was consistently detectable in AH, confirming its potential as a biomarker. Crucially, our data confirmed that TFF1 secreting cells within the tumor mass originate from RB tumor cells, not from surrounding stromal cells. IVC therapy responsive patients exhibited remarkably reduced TFF1 levels post-therapy. By contrast, RB patients` blood serum displayed low to undetectable levels of TFF1 even after sample concentration and no therapy-dependent changes were observed. Our findings suggest that compared to blood serum AH represents the more reliable source for TFF1 if used for liquid biopsy RB marker analysis in RB patients. Thus, analysis of TFF1 in AH of RB patients potentially provides a minimal invasive tool for monitoring RB therapy efficacy, suggesting its importance for effective treatment regimens.

Aim was to develop a population pharmacokinetic model for methotrexate (MTX) during high-dose treatment (HDMTX) in pediatric patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL) and to describe the sources of variability. The study included 50 patients (1-18 years) who received 3 or 5 g/m2 of HDMTX. Nonlinear mixed effects modeling approach was applied for data analysis. Parameter estimation was performed by FOCEI, whereas stepwise covariate modeling was used to assess variability factors. The final two-compartment model incorporates the effect of body weight using allometric scaling and the influence of hemoglobin and serum creatinine on MTX clearance (CL). Population pharmacokinetic values for a typical 70 kg subject were: 11 L/h for clearance (CL), 46.5 L and 16.4 L for volume of central (V1) and peripheral compartment (V2), respectively, and 0.168 L/h for intercompartmental clearance (Q). According to the final model, MTX CL decreases with increasing serum creatinine, whereas a positive effect was captured for hemoglobin. A difference of almost 30% in MTX CL was observed among patients’ hemoglobin values reported in the study. In addition to renal function and body weight, it describes the influence of hemoglobin on CL, allowing better understanding of its contribution to HDMTX disposition.

Agricultural soils serve as crucial storage sites for soil organic carbon (SOC). Their appropriate management is pivotal for mitigating climate change. To evaluate spatial and temporal changes in SOC within agricultural fields, continuous monitoring is imperative. In-field data sets of Vis-NIR soil spectra were collected on a long-term experimental site using an on-the-go spectrophotometer. Data processing for continuous SOC prediction involves a two-steps modelling approach. In Step 1, a Partial Least Square (PLSR) regression model is trained to establish a relationship between the SOC content and the spectral information also including spectral preprocesisng. In Step 2, the predicted SOC content obtained from the PLSR models is interpolated using ordinary kriging. Among the tested spectral preprocessing techniques and semivariogram models, SG and gapDer preprocessing along with a Gaussian semivariogram model, yielded the best performance resulting in a root mean square error of of 1.24 and 1.26 g kg-1. A striping effect due to the transect-based data collection was addressed by testing the effectiveness of extending the spatial separation distance, employing data aggregation, and defining the distribution based on treatment plots using block kriging. Overall, the results highlight the immense potential of on-the-go spectral Vis-NIR data for field-scale spatial-temporal monitoring of SOC.

High efficiency and safety are critical factors in ensuring optimal performance and reliability of systems and equipment across various industries. Fault Monitoring (FM) techniques play a pivotal role in this regard by continuously monitoring system performance and identifying the presence of faults or abnormalities. However, traditional FM methods face limitations in fully capturing the complex interactions within a system and providing real-time monitoring capabilities. To overcome these challenges, Digital Twin (DT) technology has emerged as a promising solution to enhance existing FM practices. By creating a virtual replica or digital copy of a physical equipment or system, DT offers the potential to revolutionize fault monitoring approaches. This paper aims to explore and discuss the diverse range of predictive methods utilized in DT and their implementations in FM across industries. Furthermore, it will showcase successful implementations of DT in FM across a wide array of industries, including manufacturing, energy, transportation, and healthcare The utilization of DT in FM enables a comprehensive understanding of system behavior and performance by leveraging real-time data, advanced analytics, and machine learning algorithms. By integrating physical and virtual components, DT facilitates the monitoring and prediction of faults, providing valuable insights into the system’s health and enabling proactive maintenance and decision-making.

Plankton monitoring by microscopy offers long-term ecological perspective of plankton com-munities but different detection approaches are biased uniquely. Genetic identification of marine plankton has become standard but is still not used in routine monitoring. This study assessed the diversity of plankton taxa using 18S high throughput sequencing from 2011-2012 from small-volume (~200ml) samples from the Water and Microplankton Sampler (WaMS) deployed on the Continuous Plankton Recorder platform (CPR). The 18S-HTS survey revealed a bias towards heterotrophic taxa, and phototrophs under 10µm within the photosynthetic community. In comparison with phytoplankton microscopic counts from the CPR survey and Western Channel Observatory station L4, only 8-12 taxonomic families were common to all three surveys, with a bias towards larger diatoms and dinoflagellate taxa in microscopy surveys. The WaMS survey detected a contrasting but complementary taxa set to that of microscopic surveys. Additional Quantitative PCR was carried out on the picoeukaryotic pelagophyte, Aureococcus anophagefferens, and the nanoeukaryotic potential harmful algae, Pseudo-nitzschia delicatissima, from 2011-2013. This confirmed the persistence presence of A. anophagefferens in the Western Channel and an elevated abundance of both species in 2011. Species specific seasonality were distinct from those of aggregrate phytoplankton groups.

Background/Objectives: The purpose of the proposed study is disclosure of correlations between the dynamics of the Breathe Rate (BR) and Heart Rate (HR) when performing the intermittent physical operation at maximum power on a cycle ergometer.Methods: The stage on the study of the General functional athlete readiness (GFAR) performed using the sports standard “Red Engine” and the cycle ergometer in 16 volunteers (10 men, 6 women) whose average age was 21±1.17 years. To determine the sports potential of the volunteers in this study, we used own Coefficient of Anaerobic Capacity (CANAC Q, beats). Continuous recording of the heart rate and respiratory rate of volunteers in the maximum power sports test was carried out by the “RheoCardioMonitor” device with an athlete functional readiness module based on the method of Transthoracic electrical impedance rheography (TEIRG).Results: The degree of correlation of functional indicators (M, HR_M, GFAR) with CANAC Q for the group in full (n=80) occurred at a very high level, which confirmed the effectiveness of using the Coefficient of Anaerobic Capacity (CANAC Q) in assessing the general functional athlete readiness of the volunteers. Conclusions: CANAC Q measured in “beats” of the heart and recorded very accurately using the method of transthoracic electrical impedance rheography (TEIRG). For this reason as promising sports PSM-system, CANAC Q can replace the methods for determining the functional athlete readiness by blood lactate concentration and maximum oxygen consumption.

Drought is considered one of the severest natural disasters and it is difficult to predict it. This review article aimed to display the state of the art of methods used to predict and monitor types of droughts. We examine more than 30 indices and models to identify the strengths and weaknesses of methods and identify gaps remaining in this field. Examples of examined indies are Palmer Drought Severity Index (PDSI), Standardized Precipitation Index (SPI), and Standardized Precipitation Evapotranspiration Index (SPEI). The research found improvement in drought modeling, however, more focus and improvement are required to monitor and predict drought types. It also found that some methods outperform others such as PDSI, SPI, SPEI, EVI, NDVI, NDWI, VCI and TCI.

Plankton monitoring by microscopy offers long-term ecological perspective of plankton communities but is biased towards those organisms that can be distinguished using the microscope. Genetic identification of marine plankton has become standard but is still not used. This study is a comprehensive study genetically measured taxa in the Western Channel of UK using a small-volume automated water sampler deployed on the CPR platform. The study present one year of high-throughput sequencing data focussing on smaller plankton and separate community to that measured by microscopy that can complement each other for a holistic view of plankton. Quantitative tests of two harmful algae show relatively high abundance of the Pelagophyte Aureococcus anophagefferens during 2011 with low nitrite levels. Three years of Pseudo-nitzschia delicatissima quantitative monitoring also shows a greater abundance of this potentially harmful taxa in 2011. Flow cytometry reveals distinct seasonal cycles with distinct timings.

Abstract: Background: Stunting is primarily a public health concern in LMIC. The involvement of Integrated Service Post cadres is one of the strategies to combat stunting in Indonesia. Objective: This study aimed to determine the effect of a short course on cadres knowledge. Method: A single group pre-post test design was conducted in Yogyakarta, Indonesia, from March to May 2022. Thirty cadres were selected based on the following criteria: willingness to participate, the number of stunted children in their Integrated Service Post (Posyandu), and full attendance at short course. The knowledge scores were measured by a structured questionnaire after short course (post-test 1) and 4 weeks later (post-test 2). We apply STATA 16 to calculate the mean difference (MD) using a t-test and Generalized Estimated Equation (GEE). Furthermore, the adequacy of the short course was evaluated with in-depth interviews. Result: On post-tests 1 and 2, cadres' knowledge of IYCF, children growth monitoring (CGM) and children development monitoring (CDM) significantly improved. The GEE analysis showed that a short course significantly improves cadres' knowledge after age control, education, occupation, and years of experience. Conclusion: Short course in-creased their affection, self-efficacy, and confidence, hence, they are capable of assisting children through home visits.

Accurately monitoring insecticide resistance in target mosquito populations is important to combating malaria and other vector-borne diseases, and robust methods are key. The “WHO susceptibility bioassay” has been used for +60 years: mosquitoes of known physiological status are exposed to a discriminating concentration of insecticide. Several changes to the test procedures have been made historically which may seem minor but could impact bioassay results. The published test procedures and literature for this method were reviewed for methodological details. Areas where there was room for interpretation in the test procedures or where the test procedures were not being followed were assessed experimentally for impact on bioassay results: covering or uncovering of the tube end during exposure, number of mosquitoes per test unit, and mosquito age. Many publications do not cite the most recent test procedures, methodological details are reported which contradict the test procedures referenced or methodological details are not fully reported. As a result, the precise methodology is unclear. Experimental testing showed that using fewer than the recommended 15-30 mosquitoes per test unit significantly reduced mortality, covering the exposure tube had no effect, and using mosquitoes older than 2-5 days old increased mortality, particularly in the resistant strain. Recommendations are made for better reporting of experimental parameters.

Abstract: The Hanqu Joint Station of the Dingbian Oil Production Plant of Yanchang Oilfield Co., Ltd is located at the edge of the desert in northern China. the bad field conditions and strong sandstorm, the hardware of computer monitoring system of Joint Station is often damaged. At the same time, the core equipment of the joint station three-phase separator oil chamber liquid level is hard to achieve high precision constant value control, the general control algorithm is difficult to meet the control requirements.This paper proposed a design scheme of a oilfield joint station computer monitoring system based on the Siemens S7-300 PLC, the hardware of the monitoring system adopts the redundancy scheme of dual monitoring computers, dual programmable logic controllers (PLCs), and dual industrial Ethernet. The BP neural network PID control algorithm was used to realize constant value control of the oil chamber liquid level of the three-phase separator of the core equipment of the joint station，and realized high control precision. The monitoring system could well adapt to the harsh environment of the scene, and showed high reliability and efficiency.

As the number of legal and illegal mining sites increase, integrative methods to evaluate the effects of mining pollution on Andes-Amazonia freshwater ecosystems are paramount. Here, we sampled water and sediments in 11 sites potentially affected by mining activities in the Napo province (Ecuador). The environmental impacts were evaluated using four lines of evidence (LOEs): water physico-chemical parameters; metal exposure concentrations; macroinvertebrate community response (AAMBI); and toxicity by conducting bioassays with Lactuca sativa and Daphnia magna. Overall, dissolved oxygen and total suspended solids were, under (&lt;80%) and above (&gt;130 mg/Ls) quality standards. Ag, Al, As, Cd, Cu, Fe, Mn, Pb and Zn in water and V, B and Cr in sediments were detected above quality standards. Nine out of eleven sites were classified as having bad environmental quality based on the AAMBI. Ranges of L. sativa seed germination in both water (37% to 70%) and sediment (0% to 65%), indicate significant toxicity. In 5 sites, neonates of D. magna showed a 25% reduction in survival compared to the control. Our integrated LOEs index ranked sites regarding their environmental degradation. Given the importance of the Andes-Amazon region, we recommend environmental impact monitoring of the mining expansion using multiple LOEs.

There are numerous challenges involved in the diagnosis and treatment of lung cancer. Globally, majority of people suffers from cancerous disease involving throat cancer, lung cancer, stomach cancer, cancerous brain tumor. Among these the most common ones is the lung cancer or lung carcinoma. The leading cause of the lung cancer is the smoking. Around 80% to 90% of deaths are caused due to Non-small cell lung cancer (NSCLC). The inadequate diagnostic techniques and low chances for the survival of lung cancer patients results from the lack of an early prognosis and incompetency in traditional therapies. However, such challenges involved in the prognosis and treatment of lung cancer are on decline with the progression in magnetic nanoparticle (MNP) technology. Many break-through discoveries and inventions have been made in the field of cancer therapy by using magnetic nanoparticles. The implication of nanotechnology has led to the recent advancement in nanomedicine field. This has encouraged the improvement in different therapeutic and diagnosis strategies employing nanotechnology. The generation of immense technological benefits for nanoparticles systems has been accredited to its remarkable nanoscale physico-chemical properties. This in turns provides the early detection of lung cancer and active drugs delivery for an improved theranostics strategy. The present review provides a general idea of the current progression in the therapeutic and prognosis purpose of magnetic nanoparticles. Further, we disclose the development in the lung cancer theranostics by functionalization of magnetic nanoparticles. The established importance of magnetic nanoparticles in the theranostics centers for lung cancer has been revealed in this paper. The challenges existing in the theranostics of lung cancer are addressed through the functioning of magnetic nanoparticles in the process.

Objectives: To investigate the value of early lactate dynamic monitoring index in predicting prognosis of patients with sepsis and septic shock. Methods: We performed our test on 50 patients. Out of 50 patients, 28 are male, and 22 are female. Prospectively studied pediatric patients with septic shock were performed. Vital signs, Lactate clearance, were obtained at presentation 6 h, 12 h, 24 h over the first 48 h of hospitalization. The therapy received, outcome parameters of mortality and duration of hospitalization were recorded. Results: The statistical data and comparative analysis showed that an average of 16.88 days after admission, 5 patients have died, 17 patients are poorly prognosis leaves the hospital, and the remaining 28 are recovered and discharged. The primary outcome variable of mean 16 days hospitalization mortality rate was 10%. Poor prognosis 34% and fully recovery 56 % were observed. In this retrospective cohort study, a lactate level of more than 2.5mmol/L was the best threshold to predict 28-day mortality among severe sepsis and septic shock patients. In our research, we found mean LC 6 h 3.08mmol/L, and after 48 h mean it is 1.79mmol/L. Significant LC 6 h found, which is 8.08mmol/L in the death group patient where 48 h mmol/L shows significant high. Poor prognosis also presents a clinical increase of lactate level high in the LC 6 h analysis, which is 3.32mmol/L. Recovered patients showed a significant improvement after administering treatment depending on the patient organ involvement and good decrease of lactate reports achieved, which is 1.20mmol/L, where admission reports show it was 1.91mmol/L in LC 6 h. Mean Heart rate 94/51mmhg, pulse 119, temperature 39℃, respiratory rate 32.26, and urine output 456 ml recorded during our study. Death patient shows a remarkable detonation of those reports but has a significant clinical report with the recovered patients. Conclusion: The early lactate dynamic monitoring index has a high value in predicting sepsis and septic shock patients' prognosis, thus worth popularizing.

The green biomass of horticultural plants contains valuable secondary metabolites (SM) which can potentially be extracted and sold. When exposed to stress, plants accumulate higher amounts of these SMs, making the extraction and commercialization even more attractive. We evaluated the potential for accumulating of the flavones cynaroside and graveobioside A in leaves of two bell pepper cultivars (Mavras and Stayer) when exposed to salt stress (100 mM NaCl), UVA/B excitation (UVA 4-5 W/m²; UVB 10-14 W/m² for 3 hours per day) or a combination of both stressors. HPLC analyses proved the enhanced accumulation of both metabolites under stress conditions. Cynaroside accumulation is effectively triggered by high-UV stress, whereas graveobioside A contents increase under salt stress. Highest contents were observed in plants exposed to combined stress. Effects of stress on overall plant performance differed significantly between treatments, with least negative impact on aboveground biomass found for high-UV stressed plants. The usage of two non-destructive instruments (Dualex and Multiplex) allowed us to gain insights in ontogenetical effects at the leaf level and temporal development of SM contents over time. Indices provided by those devices correlate fairly with amounts detected via HPLC (Cynaroside: R2 = 0.46 – 0.66; Graveobioside A: R2 = 0.51 – 0.71). The concentrations of both metabolites tend to decrease at leaf level during the ontogenetical development even under stress conditions. High-UV stress is a promising tool for enriching plant leaves with valuable SM without major effects on plant biomass. All data is available online [1].

The paper presents a case study and a model for condition monitoring of Diesel engines’ oil of urban buses, through the accompaniment of the evolution of its degradation, with the objective to implement a predictive maintenance policy. Along time, because the usage, there is some decay in the lubricant properties. However, in normal functioning conditions, the lubricants properties, at the time the manufacturers recommend its changing, regardless of they are within the safety limits. Then, based on the accompaniment of the lubricants’ oil condition, the intervals of oil replacement can be enlarged what implies the availability increasing and the corresponding production increasing of the equipment. The model presented in this paper shows its potential to be spread to other types of equipment and organisations that want can implement similar maintenance policies, to achieve the best availability based on the real equipment health conditioning conditions

Multi-view stereo (MVS) employs multi-point photography for image point positioning and three-dimensional reconstruction technology. Recently, this technology has been introduced into the monitoring of road slopes due to advances in photography and computing technology. In general, the various phases of post-image processing procedures are applied to various photographic data. In this study a novel, automated image-monitoring system is proposed to improve the ability of automatic processing. First, an Internet of things (IoT)-based digital photography system architecture was constructed to provide automatic control of camera photography and real-time transmission of image data. In addition, a visual SfM-MVS 3D reconstruction technique was used to develop related software and hardware interfaces based on the built-in Python computing framework of Photoscan Pro. The software integrates fully automatic photography, image transmission, monitoring of data processing and product release programs. The experimental results show that the system architecture can be applied to fully automatic three-dimensional monitoring of road slopes.

This paper focuses on optimal sensor positioning for monitoring activities of daily living and investigates different combinations of features and models on different sensor positions, i.e., the side of the waist, front of the waist, chest, thigh, head, upper arm, wrist, and ankle. Sixteen features are extracted and the feature importance is measured by using the Relief-F feature selection algorithm. Eight classification algorithms are evaluated on a dataset collected from young subjects and that collected from elderly subjects, with two different experimental settings. To deal with different sampling rates, signals with a high data rate are down-sampled and a transformation matrix is used for aligning signals to the same coordinate system. The thigh, chest, side of the waist, and front of the waist are the best four sensor positions for the first dataset (young subjects), with average accuracy values being greater than 95%. The best model obtained from the first dataset for the side of the waist is validated on the second dataset (elderly subjects). The most appropriate number of features for each sensor position is reported. The results provide a reference for building activity recognition models for different sensor positions, as well as for data acquired from different hardware platforms and subject groups.

This paper present a platform for airborne sensor applications using low-cost, open-source components carried by an easy-to-fly unmanned aircraft vehicle (UAV). The system, available in open-source [1], is designed for researchers, students and makers for a broad range of their exploration and data-collection needs. The main contribution is the extensible architecture for modularized airborne sensor deployment and real-time data visualisation. Our open-source Android application provides data collection, flight path definition and map tools. Total cost of the system is below 800 dollars. The flexibility of the system are illustrated by mapping the location of Bluetooth beacons (iBeacons) on a ground field and by measuring water temperatures in a lake.

This paper investigates an Energy Neutral System using Micro Energy Harvesters for a Health Monitoring Wireless Sensor Node (HM-WSN). We have implemented HM-WSN consisting of a solar cell energy harvester, a Power Management Unit (PMU) and the ucontroller, sensor and transmitter acting as load. A battery extender and a switching logic circuit for sensor node is designed to evaluate the efficiency of the proposed system. The HM-WSN senses body temperature with improvement in lifetime of coincell. The HM-WSN is built using commercially available off the shelf (COTS components and consumes 47.2uW for data being updated every 134s. It can be operated for approximately 1.32 years only on a coincell. Furthermore, the HM-WSN can be operated with solar energy at 200lux, achieving 96.36 years with a combination of a coincell with an additional capacitor of 2.2mF. It attains 4.07 years to 16.87 years lifetime with the load capacitor varying from 1mF to 1.5mF at 350lux lighting condition. With the same ambient condition and a 2mF load capacitor, HM-WSN attains complete energy autonomy.

The Fruit Harvest Helper, a mobile application developed by Northwest Nazarene University’s (NNU) Robotics Vision Lab, aims to assist farmers in estimating fruit yield for apple orchards. Currently, farmers manually estimate the fruit yield for an orchard, which is a laborious task. Fruit Harvest Helper seeks to simplify their process. While prior research efforts at NNU concentrated on developing an iOS app for blossom detection, this current research aims to adapt that smart farming application for apple detection across multiple platforms, iOS and Android. The old and new applications were designed with an intuitive user interface that is easy for farmers to use, allowing for quick image selection and processing. Unlike before, the adapted app utilizes a color ratio-based image segmentation algorithm implemented in OpenCV C++ to detect apples in apple tree images selected for processing. The results of testing the algorithm with a dataset of images indicate an 8.52% Mean Absolute Percentage Error (MAPE) and a Pearson correlation coefficient of 0.6 between detected and actual apples on the trees. These findings were obtained by evaluating the images from both the east and west sides of the trees, which was the best method to reduce the error of this algorithm. Although the Fruit Harvest Helper shows promise, there are many opportunities for improvement. These opportunities include exploring alternative machine-learning approaches for apple detection, conducting real-world testing without any human assistance, and expanding the app to detect various types of fruit. The Fruit Harvest Helper mobile application is among the many mobile applications contributing to precision agriculture, nearing readiness for farmers to use in yield monitoring and farm management.

The paper presents the final results from the research project “Urban Abacus of Building Energy performances (Abaco Urbano Energeticodegli Edifci – AUREE)” aimed at supporting the renovation and energy efficiency enhancement of urban building heritage financed by the “Ricerca Sistema Elettrico (MISE) program”. The crux of AUREE project is a Web – GIS GeoBlog portal with customized semantic dashboards aimed at sharing information on urban built environment and promoting the participation of local stakeholders to its improvement. As the latest development of this research, a workflow integrating the AUREE portal with BIM authoring and an open source IoT platform has been implemented and applied to an experimental case study concerning a public building in Carbonia (Italy). The headquarters of the sustainable energy research center Sotacarbo was selected as case study. The presented results proved that it was possible to create an open system, which could be easily consulted by "non-expert" users as well, to make available real-time monitoring data obtained from IoT sensors measuring the energy consumption, the indoor environmental conditions and the usage profiles of public buildings. The proposed open system could also be suitable to be later used as an effective tool to support the rising “energy communities”.

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.

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.

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.

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.

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.

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

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.

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.

Chronic exposure to the nephrotoxic metal pollutant, cadmium (Cd), has been associated with the pathogenesis of hypertension, but so far, the mechanism has not been well defined. We hypothesize that exposure to Cd causes a decline in the glomerular filtration rate (GFR), which in turn, causes a rise in blood pressure. Data were collected from 447 Thai subjects with a mean age of 51.1 years, of which 48.8% had hypertension, 15.4% had diabetes and 6.9% had an estimated GFR (eGFR) below 60 mL/min/1.73m2 (low eGFR). The mean blood Cd and mean urinary Cd concentrations were 2.75 and 4.23 µg/L, respectively. Prevalence odds ratio (POR) for hypertension rose twofold in those with a medium Cd burden and blood Cd levels of 0.61-1.69 µg/L. In the hypertensive group, the eGFR was inversely associated with age (β =−0.517), the Cd excretion rate (β = −0.177), and diabetes (β = −0.175). Mean eGFR in those with hypertension was 7.5 mL/min/1.73m2 lower than those who were normotensive with the same Cd body burden. In addition, higher systolic blood pressure (SBP) values were associated with older age (β = 0.243), higher BMI (β = 0.113), lower eGFR (β = −0.106) and diabetes (β = 0.216). Mean SBP in those who had low eGFR and medium and heavy Cd body burden was 9.5 mmHg higher than those with the same Cd body burden and a normal eGFR. Thus, chronic environmental exposure to Cd that produces urinary and blood Cd levels of 0.57-0.61 µg/L, increases the risk of hypertension, and this could be mediated by a declining GFR.

Emerging evidence demonstrated that using a new manufacturing technology to produce γ-aminobutyric acid (GABA)-fortified oolong (GO) tea could relieve human stress and exert versatile physiological benefits. The purpose of this human research aims to investigate therapeutic effects of daily GO tea consumption on the improvement of blood pressure, relaxation-related brain waves and quality of life (QOL) during a period of 28 consecutive days. Total polyphenols, major catechins and free amino acids were analyzed via HPLC assay. Changes of heart rate, blood pressure, α-brain wave (index of relaxation) and eight-item QOL score were investigated on day 0, 7, 14, 21 and 28, respectively. The chemical analysis results showed that GO tea contained the most abundant amino acids and GABA, contributing to the relaxation activity. Among all study participants, daily drinking GO tea could reduce systolic blood pressure on day 21 and diastolic blood pressure on day 28 (p &lt; 0.05, respectively). For participants with pre-hypertension, GO tea could effectively reduce heart rate, systolic and diastolic blood pressure on day 28 (p &lt; 0.05). At the end of the study, incremental changes in alpha-brain wave and QOL scores were also demonstrated (p &lt; 0.05, respectively). This study recommended that GO tea might potentially serve as a natural source of alternative therapy to benefit blood pressure, stress-relief and QOL.

Astragaloside IV (AIV) – triterpenoid saponin from the Astragalus mongholicus roots with the proved acetylcholinesterase (AChE)-inhibitory capability was used as the substance with the potential to attenuate memory impairment. Scopolamine (SCOP), antagonist of muscarinic cholinergic receptors and lipopolysaccharide (LPS), neuroinflammation inducer were used to impair memory processes in the passive avoidance (PA) test in mice. This memory impairment in the SCOP-treated mice was attenuated by the earlier intraperitoneal (ip) administration of AIV in the dose of 25 mg/kg. The reduction of memory impairment by LPS was not observed, therefore AIV does not reverse memory impairments through the anti-inflammatory mechanisms. All the studied doses of AIV did not affect basic locomotor activity of mice. As a result of the post-mortem analysis of mice body tissues, the largest content of AIV was determined in the kidneys, then in the spleen, liver and the smallest one in brain by mass spectrometry.

Bacteremia and fungemia are significant causes of morbidity and mortality which frequently occur as co-infections with viral respiratory infections including SARS-CoV-2. It was aimed to evaluate the microorganisms isolated from blood cultures of SARS-CoV-2 positive and negative patients and investigate their antimicrobial resistance patterns. A retrospective analysis was performed with the total number of 22,944 blood cultures sent to the laboratory between November 2020 and December 2021. Blood cultures were performed on the BD Bactec automated system. Identification was performed using conventional methods, VITEK-2 and MALDI-TOF MS. Antibacterial/antifungal susceptibility tests were performed according to EUCAST/CLSI recommendations. SARS-CoV-2 tests were performed with RT-PCR. It was detected 1,630 culture positivity belonging to 652 patients. Totally 633 of 652 patients were tested for SARS-CoV-2; 118 (18.6%) were positive and 515 (81.3%) were negative. The bacteria and fungi isolated at the high-est rate in SARS-CoV-2 positive patients were methicillin-resistant coagulase negative staphylococci (MR-CoNS) (21.5%), Escherichia coli (12.4%), Klebsiella pneumoniae (12.4%), Candida albicans (1.65%) and Candida glabrata complex (1.65%); while in negative patients, E. coli (21.3%), MR-CoNS (13.5%), K. pneumoniae (12.05%), C. albicans (2.1%), Candida parapsilosis (1.1%) and Candida tropicalis (0.9%). The fact that the most common isolate was MR-CoNS in SARS-CoV-2 positive patients (p = 0.028); the detection of Acinetobacter baumannii was more frequent (p = 0.001) and the isolation of carbapenem-resistant K. pneumoniae was at a higher rate than in SARS-CoV-2 negative patients; also, the increase in multidrug-resistant strains indicate that healthcare-associated infec-tions should not be disregarded while focusing on the outbreak.

Per- and polyfluoroalkyl substances (PFASs) are a group of fluorinated, organic, man-made chemicals; they do not occur naturally in the environment. This study aimed to determine the profile and content of PFASs in volunteers’ blood plasma and urine after fermented red beetroot juice consumption and correlated it with the blood parameters. During 42 days, 24 healthy volunteers intake 200 mL/60 kg of body weight fermented red beetroot juice. PFASs were analyzed using micro-HPLC-MS/MS method. Five perfluoroalkyl substances were found in human body fluids. After juice consumption, PFASs, due to the consumption of food contaminated with them, was discovered that for perfluorocarboxylic acids, a downward trend was observed, while for perfluoroalkane sulfonates, their plasma content showed a statistically significant upward trend. Analysis of the hematology parameters indicated that the intake the fermented red beetroot juice showed a significant decrease in mean corpuscular volume (MCV), platelets concentration, mean platelet volume (MPV), platelet large cell ratio (P-LCR) at the significance level p < 0.01, and he-matocrit (p < 0.05). On the other hand, the dietary intervention also indicated a significant (p < 0.01) increase corpuscular/ cellular hemoglobin concentration (MCHC). In the case of blood biochemi-stry, no significant change in blood samples after intake the fermented beetroot juice was observed. However, a decreasing tendency of total cholesterol and low-density lipoprotein concentration (LDL-C) were observed. Based on the presented results, there is a need to analyze and monitor health-promoting food regarding undesirable substances and their impact on consumer health.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women, characterized by fluid-filled sacs in the ovaries and various symptoms including high androgen levels, endometrial irregularities, and cysts. While the cause of PCOS is unknown, it has been linked to genetic, endocrine, and metabolic factors, and there are several treatment options, including lifestyle modifications, medications, and surgery. Natural products, such as medicinal plants and fruits, are being explored as potential treatments for PCOS due to their bioactive compounds with pharmacological effects related to antioxidant, antimicrobial, anticancer, and antidiabetic properties. Some of these compounds improve insulin sensitivity, reduce inflammation, and enhance glucose metabolism, which is beneficial for women with PCOS. This review examined the effects of natural products on PCOS, including their effects on ovarian histological changes, blood glucose, sex hormones, and lipid profile, based on animal and human studies. This study suggests that the use of natural products as complementary medicine can be a promising resource for the development of effective therapeutics for PCOS, but that further research is needed to fully understand their benefits

Hypertension and arterial stiffness are the main factors contributing to cardiovascular disease. L-citrulline, a nitric oxide precursor, has been proposed as a blood pressure-lowering intervention. This study aimed to investigate the impact of L-citrulline on central and peripheral blood pressure, arterial stiffness, and muscle oxygenation at rest and during an isometric knee extension exercise protocol. Twelve older males received 6 g of L-citrulline or a placebo for six days using a double-blind crossover design. Blood hemodynamics parameters (i.e., arterial and brachial systolic and diastolic blood pressure, mean arterial pressure, pulse pressure, heart rate), arterial stiffness (i.e., augmented pressure, augmentation index, forward, backward wave pressure and carotid-femoral pulse wave velocity) and muscle oxygenation [i.e., oxyhemoglobin (Δ[O2Hb]) and deoxyhemoglobin (Δ[HHb]), total hemoglobin concentration (Δ[tHb]) and tissue saturation index (TSI%)], were measured at baseline, post-supplementation and during isometric exercise. No significant effects of L-citrulline supplementation were observed at rest or during exercise on blood pressure, arterial stiffness, and muscle blood flow. Both central and peripheral blood pressure were increased during the exercise, which is consistent with isometric contractions. The results of the present study question the efficacy of short-term L-citrulline in decreasing blood pressure at rest or attenuating blood pressure increases during isometric exercise.

In this paper, the feasibility of automated and accurate in vivo measurements of vascular parameters continuously and non-invasively using ultrasound sensor is presented. Vascular parameters such as pulse wave velocity (PWV), blood pressure (BP), arterial compliance (AC) and stiffness index (SI) are affluent indicators of cardiovascular disorders and needs to be monitored non-invasively and continuously during surgeries and follow-up procedures. Cuff based or invasive catheter techniques are considered as gold standard to measure BP and are fed manually to compute AC and SI which employ imaging algorithms. In this context, a Continuous and Non-Invasive Vascular Stiffness and Arterial Compliance Screener (CaNVAS) is developed to measure said parameters continuously and non-invasively using ultrasound sensor. Acoustic waves of 5 MHz (2.2 – 10 MHz) are driven through target arterial walls, reflected echoes captured, pre-processed and frequency shift is used to calculate PWV. It is observed that PWV measured using CaNVAS varies exponentially with BP values obtained from sphygmomanometer (BPMR-120) and this relationship is used to compute instantaneous values of BP. The proposed device is validated by performing measurements on 250 subjects in pre and post exercise conditions and found to have 95% accuracy and an average of 12.5% coefficient of variation.

The importance of PAs for CNS functions are well known. Less clear is, however, where PAs in the brain are derived from. Principally, there are three possibilities: (i) intake by nutrition, release into the bloodstream, and subsequent uptake from CNS capillaries, (ii) products of parenchymatous organs as the liver, and again uptake from CNS capillaries, and (iii) uptake of precursors such as arginine from the blood and subsequent local biosynthesis of polyamines within the CNS.The present investigation aimed to unequivocally answer the question, whether PAs, especially the higher ones like SPD and SPM can or cannot be taken up into the brain from the bloodstream. For this purpose a biotin-labelled analogue of SPM was synthesized, characterized, and used to visualize its uptake into brain cells subsequent to application to surviving brain slices, to the intraventricular space, or to the bloodstream.In surviving slices uptake of B-X-SPM is massive into protoplasmic and absent in fibrous type astrocytes. It is also taken up by neurons but to a lesser degree. Under in-vivo conditions astrocyte uptake of biotinylated SPM also is massive from the brain interstitial fluid subsequent to intraventricular application. In contrast, following intracardial injection there is no uptake from the bloodstream, indicating that the brain is completely dependent on the local synthesis of polyamines.

In order to realize the accurate measurement of wearable sphygmomanometer, this paper selects the micro electro mechanical system (MEMS) pressure sensor with small size, low cost and high accuracy, and proposes a flexible packaging method combining Parylene and Polydimethylsiloxane (PDMS). The flexible packaging sensor protects the sensor chip while ensuring the comfort of the measured person. It can be worn for a long time, and the encapsulated sensor has good accuracy and sensitivity. At the same time, the encapsulated MEMS pressure sensor was used to collect good pulse signals and extract multiple pulse wave characteristic parameters. A blood pressure measurement method based on the combination of arterial tonometry method and pulse wave parameters method was proposed, and multiple machine learning algorithms were compared and analyzed to select the algorithm model with the smallest error as the optimal regressor. The experimental results show that the blood pressure measurement method combining the arterial tonometry method and the pulse wave parameters method can effectively improve the accuracy of blood pressure measurement. The experimental results demonstrate that the combination of arterial tonometry and pulse wave parameter methods can effectively enhance the accuracy of blood pressure measurement, with the random forest model serving as the optimal regressor. The average deviation between the systolic blood pressure measured by our self-made sphygmomanometer and the commercial sphygmomanometer was 0.86mmHg, with a standard deviation of 4.04mmHg. The average deviation of diastolic blood pressure was 0.63mmHg, with a standard deviation of 5.15mmHg, meeting the AAMI standard for clinical practice.

Abstract Coenzyme Q10 (CoQ10) has a number of vital functions in all cells, both mitochondrial and extra-mitochondrial. In addition to its key role in mitochondrial oxidative phosphorylation, CoQ10 serves as a lipid soluble antioxidant, plays an important role in fatty acid beta-oxidation and pyrimidine and lysosomal metabolism, as well as directly mediating the expression of a number of genes, including those involved in inflammation. Because of the multiplicity of roles in cell function, it is not surprising that deficiency of CoQ10 has been implicated in the pathogenesis of a wide range of disorders. CoQ10 deficiency is broadly divided into primary and secondary types. Primary CoQ10 deficiency results from mutations in genes involved in the CoQ10 biosynthetic pathway. In man, at least 10 genes are required for the biosynthesis of functional CoQ10, a mutation in any one of which can result in a deficit in CoQ10 status. Patients may respond well to oral CoQ10 supplementation, although the condition must be recognised sufficiently early, before irreversible tissue damage has occurred. In this article, we have reviewed clinical studies (up to March 2023) relating to the identification of these deficiencies, and the therapeutic outcomes of CoQ10 supplementation.

Theoretical approaches were applied to study the effect of magnetic field and heat transfer on the flow of blood plasma through an asymmetric arterial segment. The plasma was considered to be unsteady, laminar and an incompressible fluid through non-uniform arterial segment in a two-dimensional flow. Axial velocity, pressure gradient, stream function and pressure shift per wavelength were evaluated in blood plasma flow in arteries by use of coupled linear partial differential equations, solved with the help of Finite difference method. The corresponding initial and boundary conditions were obtained by discretizing the flow channel. The effect of magnetic field on blood plasma in arteries was determined by creating a magnetic field gradient through the application of a varying strength of magnetic field on the flow. Heat transfer characteristics due to applied magnetic field and viscosity of blood was obtained by use of linear partial differential equations to determine varying temperature conditions in heat transfer characteristics. Numerical results for velocity profiles, magnetic profiles and temperature profiles were obtained to characterize blood plasma viscosity by use of various non-dimensional parameters. The results were graphically presented using MATLAB software. The results obtained helped in analyzing theoretically the effects of magnetic field and heat transfer in arterial plasma flow.

Despite the recent advances in melanoma therapy, the need for new targets and novel approaches to therapy is urgent. We previously reported melanoma actives that work via binding and downregulating spliceosomal proteins hnRNPH1 and H2 (Palrasu et al., 2019). Given lack of knowledge about side effects of using spliceosomal binders in humans, an acute toxicity study was conducted to evaluate these compounds in mice. Male and female mice were treated with compounds 2155-14 and 2155-18 at 50mg/kg/day via subcutaneous injections and the clinical signs of distress were monitored for 21 days and compared with control mice. Additionally, effect of the leads on blood chemistry, blood cell counts, and organs was evaluated. No significant changes were observed in the mice body weight, blood cell count, blood chemistry, or organs following the compound treatment. The results show that our compounds 2155-14 and 2155-18 are not toxic for the study period of three weeks.

The onset of embryonic heart beating may be regarded as the defining feature for the beginning of personal human life. Clarifying the timing of the 1^st human heartbeat, therefore, has religious, philosophical, ethical, and medicolegal implications. This article reviews the historical and contemporary sources of knowledge on the beginning of human heart activity. Special attention is given to the problem of the determination of the true age of human embryos and to the problem of visualization of the human embryonic heart activity. It is shown that historical and current textbook statements about the onset of blood circulation in man do not derive from observations on living human embryos but derive from the extrapolation of observations on animal embryos to the human species. This fact does not preclude the existence of documented observations on human embryonic heart activity: Modern diagnostic (ultrasound) and therapeutic (IVF) procedures facilitate the visualization of early embryonic heart activity in precisely dated pregnancies. Such studies showed that the human heart started its pumping action during the 4^th post-fertilization week. A small number of direct observations on the heart activity of aborted human embryos were reported since the 19^th century but did not receive much recognition by embryologists.

Background: Evidence supports a causal relationship between circadian disturbance and impaired glucose homeostasis. Method: To determine the effect of a nursing educational intervention on improving healthy sleep, a parallel, open-label clinical trial in subjects with Impaired Fasting Glucose (IFG) or Type 2 Diabetes Mellitus (T2DM) and 18 and older was performed. Study variables were sex, age, fasting glucose, glycated hemoglobin A1c (HbA1c), Pittsburgh Sleep Quality Index (PSQI), sleep duration and efficiency, BMI, antidiabetic treatment and diet and physical exercise. An individual informative educational intervention was carried out following a bidirectional feedback method. It was intended to develop skills to improve sleep through 9 simple tips. An analysis of covariance was performed on all the mean centered outcome variables controlling for the respective baseline scores. Results: After the intervention, in the experimental group, PSQI dropped, the duration and quality of sleep increased. Further, a decrease in fasting glucose and in HbA1c levels was observed. Conclusion: The proposed intervention has proven to be effective to improve sleep quality, time, and efficiency and in only 3 months, to achieve a decrease in fasting glucose and HbA1c levels. These findings support the importance of sleep and circadian rhythms education focused on improving in T2DM or IFG.

Background: Research continues to search for blood-based biomarkers sensitive to Alzheimer’s disease (AD) pathology during the initial stages when symptoms of cognitive decline are not yet apparent. A blood-based biomarker candidate is metalloprotein p53, the conformation of which was previously found to be altered in peripheral cells from individuals with mild cognitive impairment (MCI) and AD, presenting as an unfolded p53 (U-p53) conformational variant. Methods: Plasma samples from the well-characterized Australian Imaging, Biomarkers, and Lifestyle (AIBL) cohort were used to identify the clinically relevant AZ 284^® peptide, specifically present in samples from individuals with symptomatic AD. The AZ 284^® peptide, which is a marker of the U-p53 conformational variant (U-p53^AZ), was identified by immunoprecipitation (IP) with a novel U-p53 conformational variant-specific antibody followed by liquid chromatography (LC) tandem mass spectrometry (MS/MS) and protein sequencing. Using IP-LC surface-activated chemical ionization (SACI) MS/MS analysis, the prognostic and diagnostic performance of U-p53^AZ were examined in the longitudinal AIBL cohort, including 252 plasma samples derived from 214 elderly individuals. For the prognostic analyses, U-p53^AZ levels were assessed at 36, 72, and 90 months after baseline assessment. Results: The prognostic performance of U-p53^AZ to predict the progression to AD from preclinical or prodromal AD was high, with area under the receiver operating characteristic curve (AUC) values close to or above 0.90. Furthermore, U-p53^AZ predicted the progression to AD more than 6 years prior to symptom onset with positive and negative predictive values of about 90%. Additionally, the estimated prognostic performance of U-p53^AZ was superior to other main risk factors (i.e., age, sex, and either alone or in combination with amyloid status. Furthermore, U-p53^AZ had high diagnostic performance to differentiate cognitively normal individuals from those with AD (AUC values >0.88). Conclusion: These findings support the use of U-p53^AZ as a prognostic blood-based biomarker accurately predicting the progression to AD dementia during the preclinical and prodromal stages at least 6 years before receiving the clinical diagnosis of AD dementia.

Here, we review findings and trends in sleep research in 2020-2021 demonstrating how COVID-19 and sleep disorders can induce the BBB leakage via neuroinflammation, which might contribute to the 'coronasomnia' phenomenon. The new studies suggest that the controlling of sleep hygiene and quality should be incorporated into the rehabilitation of COVID-19 patients. We also discuss perspective strategies for prevention of COVID-19-related BBB disorders. We demonstrate that sleep might be a novel biomarker of the BBB leakage and the analysis of sleep EEG patterns can be a breakthrough non-invasive technology for diagnosis of the COVID-19-caused BBB disruption.

The neurovascular niche is crucial for constant blood supply and blood-brain barrier (BBB) function and is altered in a number of different neurological conditions, making this an intensely active field of research. Brain vasculature is unique for its tight association of endothelial cells with astrocytic endfeet processes. Separation of the vascular compartment by centrifugation-based methods confirmed enrichment of astrocytic endfeet processes, making it possible to study the entire vascular niche with such methods. Several centrifugation-based separation protocols are found in the literature; however, with some constraints which limit their applicability and the scope of the studies. Here, we describe and validate a protocol for physically separating the neurovascular niche from the parenchyma, which is optimized for smaller tissue quantities. Using endothelial, neuronal and astrocyte markers, we show that quantitative Western blot-based target detection can be performed of both the vascular and parenchymal fractions using as little as a single mouse brain hemisphere. Validation of our protocol in rodent stroke models by detecting changes in serum albumin signals and astrocyte activation, i.e. increased glial fibrillary acidic protein expression, between the ipsilateral and the lesion-free contralateral hemisphere demonstrates this protocol as a new way of detecting BBB breakdown and astrogliosis, respectively.

Objective: On March 11, 2020 the WHO declared that COVID-19 is pandemic. Among the risk factors for many infectious diseases, a role of the ABO blood group system is reported in the literature. We argue whether it is necessary to investigate the relationship between ABO blood groups and susceptibility to SARS-CoV-2 infection and if we should consider some blood groups as potential risk factors for COVID-19. Results: Based on the scientific evidence reported in this letter, we believe that further studies are needed to investigate how the ABO polymorphism influences the host susceptibility, individual response and clinical risk for SARS-CoV-2 infection.

Background: Besides anemia, iron deficiency may cause more subtle symptoms including those of the restless legs syndrome (RLS), the chronic fatigue syndrome (CFS) or sleeping disorders. Objective: The aim of this pre-planned secondary analysis was to compare the frequency and severity of symptoms associated with iron deficiency before and after (intravenous or oral) iron supplementation in iron deficient blood donors. Methods/Design: Prospective, randomized, controlled, single centre trial. (ClinicalTrials.gov: NCT01787526). Setting: Tertiary care center in Graz, Austria Participants: 138 female and 38 male whole blood and platelet apheresis donors aged ≥18 and ≤65 years with iron deficiency (ferritin ≤30ng/ml at the time of blood donation). Interventions: Intravenous iron (1 g ferric carboxymaltose, n=86) or oral iron supplementation (10 g iron fumarate, 100 capsules, n=90). Measurements: Clinical symptoms were evaluated by a survey before iron therapy (visit 0, V0) and after 8-12 weeks (visit 1, V1) including questions about symptoms of RLS, CFS, sleeping disorders, quality of life and symptoms like headaches, dyspnoea, dizziness, palpitations, pica and trophic changes of fingernails or hair. Results: We found a significant improvement in the severity of symptoms for RLS, fatigue and sleep quality (p<0.001). Furthermore, a significant decrease of headaches, dyspnoea, dizziness and palpitations was reported (p<0.05). There was no difference between the type of iron supplementation (intravenous versus oral) and clinical outcome data. Conclusion: Iron supplementation in iron deficient blood donors may be an effective strategy to improve symptoms related to iron deficiency and the wellbeing of blood donors.

Cerebral blood flow (CBF) decreases across the lifespan, and chronic conditions such as dementia and stroke accelerate this decline. Impaired CBF results in reduced delivery of oxygen and nutrients, which can damage the brain over time. Thus, there is a need to identify lifestyle interventions including diet and exercise to maintain CBF with aging and in the presence of chronic disease. In the present study, we used transcranial Doppler ultrasound to record middle cerebral artery velocity (MCAv), a surrogate measure of CBF, during moderate-intensity exercise in sedentary, cognitively-normal older adults (N = 90). A multiple linear regression model (F(4, 85) = 3.21, p = 0.02) showed self-reported omega-3 supplement use significantly moderated the association between age and mean exercising MCAv in these individuals (p = 0.01). Older age was associated with lower exercising MCAv in the group not taking omega-3 supplements, while exercising MCAv showed no decline with increasing age in the group who reported omega-3 supplement use. These findings suggest omega-3 supplementation may have an important role in the preservation of CBF with aging.

Abstract: The broad clinical use of synthetic vascular grafts for vascular diseases is limited by their thrombogenicity and low patency rate, especially for vessels with a diameter inferior to 6 mm. Alternatives such as tissue-engineered blood grafts (TEBGs) have gained increasing interest. Among the different manufacturing approaches, 3D bioprinting presents numerous advantages and enables the fabrication of multi-scale, multi-material, and multicellular tissues with heterogeneous and functional intrinsic structures. Extrusion-, inkjet- and light-based 3D printing techniques have been used for the fabrication of TEBG out of hydrogels, cells, and/or solid polymers. This review discusses the state-of-the-art research on the use of 3D printing for TEBG with a focus on the biomaterials and deposition methods.

The peripheral lymphatic system plays a crucial role in the recovery mechanisms after many pathological changes, such as infection, trauma, vascular, or metabolic diseases. The lymphatic clearance of different tissues from waste products, viruses, bacteria and toxic proteins significantly contributes to the correspondent recovery processes. However, understanding of the meningeal lymphatics functions is a challenging problem. The exploration of mechanisms of lymphatic communication with brain fluids as well as the role of the lymphatic system in the brain drainage, clearance and recovery are still in its infancy. Here we review novel concepts on the anatomy and physiology of the lymphatics in the brain, which warrant a substantial revision of our knowledge about the role of lymphatics in the rehabilitation of the brain functions after neural pathologies. We discuss a new vision on how to recruit the meningeal lymphatics by the opening of blood-brain barrier as a trigger mechanism of activation of the meningeal lymphatic drainage. This leads to innovative strategies in neurorehabilitation therapy.

BACKGROUND G6PD deficiency is an inherited an X-linked recessive condition leading to insufficient levels of glucose-6-phosphate dehydrogenase, thus causing hemolytic anaemia under certain conditions. METHODS Our study is explorative for cases admitted to Jordan University Hospital. The studied parameters include demographics, clinical manifestations, biochemical markers including Hb level, WBC count, liver enzymes, and blood grouping. RESULTS Most of the patients were admitted to the emergency unit (53.13%). Individuals who were Rh-positive represented 57.81%, while patients of AB blood group accounted for 75%. The mean values were 4.81 years (age), 29.06 hours (time-to-hospital admission), 38.10 degree Celsius (temperature), 6.11 gm/dl (Hb), 13242.19 (WBC count), 343.20 U/L (S. ALP), and 50.98 IU/L (S. ALT). There was no significant difference between males and females or between favism-induced versus drug-induced hemolytic episodes. AB and Rh positive blood groups are of protective effect in relation to liver enzymes. Patients who were admitted to the hospital within 24 hours from having clinical manifestations had a better prognosis. CONCLUSION This study is the first inferential research on G6PD deficiency from the Middle East to explore cases from one of the largest healthcare centres in Jordan. The role of blood grouping should be investigated prospectively.

The tumor microenvironment is known to have increased levels of cytokines and metabolites, such as glutamate, due to their release from the surrounding cells. A normal cell around the tumor that responds to the inflammatory environment is likely to be subsequently altered. We will discuss how these abnormalities will support tumor survival via the actions of gap junctions (GJs) and hemichannels (HCs) which are composed of hexamer of connexin 43 (Cx43) protein. In particular, we will discuss how GJ intercellular communication (GJIC) in glioma cells, the primary brain tumor, is a regulatory factor and its attenuation leads to tumor invasion. In contrast, the astrocytes, which are normal cells around the glioma, are "hijacked" by tumor cells, either by receiving the transmission of malignant substances from the cancer cells via GJIC, or perhaps via astrocytic HC activity through the paracrine signaling which enable the delivery of these substances to the distal astrocytes. This astrocytic signaling would promote tumor expansion in the brain. In addition, brain metastasis from peripheral tissues has also been known to be facilitated by GJs formed between cerebral vascular endothelial cells and cancer cells. Astrocytes and microglia are generally thought to eliminate cancer cells at the blood brain barrier. In contrast, some reports suggest they facilitate tumor progression as tumor cells take advantage of the normal functions of astrocytes that support the survival of the neurons by exchanging nutrients and metabolites. In summary, GJIC is essential for the normal physiological function of growth and allowing the diffusion of physiological substances. Therefore, whether GJIC is cancer promoting or suppressing may be dependent by what permeates through GJs, when it is active, and to which cells. The nature of GJs, which has been ambiguous in brain tumor progression, will need to be re-visited and understood together with new findings on Cx proteins and HC activities.

Shiga toxin (Stx) produced by Escherichia coli is the main pathogenic factor of diarrhea-associated hemolytic uremic syndrome (HUS), which is characterized by obstruction of renal microvasculature by platelet-fibrin thrombi. It is well known that the oxidative imbalance generated by Stx induces platelet activation, contributing to thrombus formation. Moreover, activated platelets release soluble CD40 ligand (sCD40L) which in turn contributes to oxidative imbalance, triggering the release of reactive oxidative species (ROS) on various cellular types. The aim of this work was to determine if the interaction between the oxidative response and platelet-derived sCD40L participates in the pathogenic mechanism during HUS. Activated human glomerular endothelial cells (HGEC) by Stx2 induced platelets to adhere to them. Although platelet adhesion did not contribute to endothelial damage, high levels of sCD40L were released to the medium. The release of sCD40L by activated platelets was inhibited by antioxidant treatment. Furthermore, we found increased levels of sCD40L in plasma from HUS patients, which were also able to trigger the respiratory burst in monocytes, in a sCD40L-dependent manner. Thus, we concluded that platelet-derived sCD40L and the oxidative response are reciprocally stimulated during Stx2-associated HUS. This process may contribute to the evolution of glomerular occlusion and the microangiopathic lesions.

The nature of the interaction between Th17 cells and the blood-brain barrier (BBB) is critical for the development of autoimmune inflammation in the central nervous system (CNS). TNF-a or IL-17 stimulation is known to enhance the adherence of Th17 cells to the brain endothelium. The brain endothelial cells (bEnd.3) express VCAM-1, the receptor responsible for inflammatory cell adhesion, which binds VLA-4 on migrating effector lymphocytes at the early stage of brain inflammation. The present study examines the effect of the pro-inflammatory cytokines TNF-a and IL-17 on the adherence of Th17 cells to bEnd.3 The bEnd.3 cells were found to increase production of CCL2 and CXCL1 after stimulation by pro-inflammatory cytokines, while CCL2, CCL5, CCL20 and IL17 induced Th17 cell migration through a bEnd.3 monolayer. This interaction between Th17 cells and the brain endothelium appears to be mediated by VCAM-1 and some chemotactic cytokines. This observation may suggest potential therapeutic targets for the prevention of autoimmune neuroinflammation development in the CNS.