The coevolution of species drives diversity in animals and plants and contributes to natural selection, whereas in host–parasite coevolution, a parasite may complete an incomplete evolutionary/developmental function by utilizing the host cell’s machinery. Analysis of related older data suggests that Plasmodium falciparum (P. falciparum), the pathogen of malaria tropica, cannot survive outside its human host because it is unable to perform the evolutionarily first protein glycosylation of serologically A-like, O-GalNAcα1-Ser/Thr-R, Tn antigen (“T nouvelle”) formation, owing to its inability for synthesizing the amino sugar N-acetyl-d-galactosamine (GalNAc). This parasite breaks the species barrier via hijacking the host's physiological A-like/Tn formation through abundantly expressing serine residues and creating hybrid A-like/Tn structures, which in the human blood group O(H) are attacked by the germline-encoded nonimmune polyreactive immunoglobulin M (IgM), exerting the highly anti-A/B/H-aggressive isoagglutinin activities. These activities physiologically undergo the ABO(H) blood group phenotype formation, occurring on the surfaces of red blood cells (RBC), epithelial and endothelial cells and on plasma proteins by identical glycosylation, performed by the ABO(H)-allelic glycotransferases, phenotypically downregulating the anti-A/B/H-reactive IgM (isoagglutinin) activities in the non-O blood groups. ABO(H) phenotype diversity, this way glycosidically linked and molecularly connected to humoral immunity, becomes exposed to the evolution.

Aim: To develop an index for quantitative assessment of the upper limb motor function in children with cerebral palsy before and after robot-assisted therapy. Method: An upper limb motor function index was developed using kinematic, surface electromyography and three-axis inertial measurements unit data collected from 15 children with cerebral palsy (CP) and 15 typically developed children. Children with CP underwent 18 robot-assisted therapy sessions with the REAplan device. All children were evaluated, using kinematic data from the REAplan, electromyography and three-axis inertial measurements unit readings from its accelerometer. A principal component analysis was conducted to produce an evaluation index, which is able to detect the deviation from the upper limb motor function of typically developing children group. Children with CP were evaluated twice before and after the intervention with Box and Blocks test and Finger-To-Nose test. The discriminative and concurrent validity of the upper limb motor function index were investigated. Results: The upper limb motor function index was higher in children with CP post therapy (p<0.001). Finger-To-Nose test values improved after robot-assisted therapy (p<0.03). A weak but positive correlation was observed between upper limb motor function index and clinical tests (r=0.012, p=0.95 and r=0.13, p= 0.54 for Box and Blocks test and Finger-To-Nose test respectively). Interpretation: The upper limb motor function index successfully differentiated between the typically developing children and children with CP and was effective in assessing the improvement of the upper limb motor function after robot-assisted therapy. The upper limb motor function index could be extended to assess and monitor rehabilitation therapies of other populations, such as those with stroke and Parkinson’s disease.

The blood counts of α thalassemia carriers (α-thal) are similar to those of β thalassemia carriers, except for Hgb A2 that is not elevated. The objective of this study was to determine whether mathematical formulas are effective for detecting suspected α-thal. The data were obtained from the database of the prevention program for detecting couples at risk for having a child with hemoglobinopathy. RBC indices were analyzed using mathematical formulas and the sensitivity and negative predictive value (NPV) calculated. Among 1334 blood counts suspected α-thal analyzed, only the Shine&Lal and the Support Vector Machine formulas revealed high sensitivity and NPV. Sensitivity was 85.54 and 99.33% and NPV 98.93 and 99.93%, respectively. Molecular defects were found in 291, 81 had normal α genes. Molecular analysis was not performed in 962. Based on these results, mathematical formulas incorporating one of these reliable formulas for detecting suspected α or β thalassemia carriers in the program of the automatic analyzers can flag these results and increase the awareness of the primary physicians about the carrier risk and send an alert with a recommendation for further testing.

Ischemic stroke (IS) is a group of vascular disease concomitant with high morbidity and mortality. Berberine is a bioactive substance and it has known to improve stroke, but the mechanism is yet to be proven. Mice were fed with BBR for 14 days. Then, mice were made into MCAO/R models. Neurological score, infarct volume, neuronal damage and markers associated with inflammation were detected. We tested the changes of intestinal flora in model mice after BBR administration by 16SrRNA sequencing. Chromatography-mass spectrometry was used to detect butyrate chemically. Tissue immunofluorescence was used to detect the changes of microglia and astroglia in mice brain. Our findings suggest that berberine improves stroke outcomes by modulating gut microbiota. Specifically, after MCAO/R mice were given berberine, beneficial bacteria producing butyric acid increased significantly, and the mice also had significantly higher levels of butyric acid. Administration of butyric acid and an inhibitor of butyric acid synthesis, heptyl-coA, showed that butyric acid improved stroke outcomes in model mice. In addition, butyric acid could inhibit the activation of microglia and astrocytes in the brain of model mice, thereby inhibiting the release of inflammatory cytokines IL-6, IL-1β, TNF-α and improving stroke outcomes. Our results suggest that berberine may improve stroke outcomes by modulating the gut flora to increase the abundance of butyric acid. These findings elucidate the mechanisms by which berberine improves stroke outcomes and provide some basis for clinical treatment.

The affected upper limb in children with Unilateral Spastic Cerebral Palsy (US CP) has motor and somatosensory impairments, that contribute negatively to children’s bimanual performance and quality of life. Mirror Therapy (MT) is being studied to become an approachable intensive and home-based therapy, suitable for children with US CP. The aim of this study is to examine the feasibility of a 5-week home-based program of MT for children with US CP. Six children aged 8-12 years old performed the therapy, five days per week, 30 minutes per day. A minimum of an 80% of compliance was required. The evaluations included the feasibility of the therapy (compliance, total dosage, perceived difficulty of the exercises, and losses of follow-ups and evaluations), the bimanual performance, the somatosensory function and the quality of life at baseline, at the end of the intervention, and at 1-month follow-up. All children completed the therapy and were included in the analysis. The total accomplishment was 86.47 ± 7.67. The perceived difficulty of the exercises ranged from 2,37 to 4,51. As a conclusion, a home-based program of Mirror Therapy is suitable and feasible for children with US CP.

Hippotherapy is a popular rehabilitation method for children with cerebral palsy (CP), which is done by riding an actual horse or a horse riding simulator (HRS) device. Riding a real horse is more expensive than using an HRS device due to its high maintenance cost. However, most HRS devices commonly sold in the market are designed as exercise devices, not rehabilitation devices. Most of them are designed to simulate a horse's walk, trot, canter, or gallop gait at various speeds. Hippotherapy aims to improve the walking ability of CP patients. Therefore, the device should aim to replicate the walking gait of a healthy human, the end goal of hippotherapy. This problem motivates us to design and build a specialized HRS device replicating the walking gait of a healthy human that is suitable for hippotherapy, which is achievable by simulating a horse walking gait with several adjustments. We first studied and observed the walking gait cycle of a horse, then analyzed and derived a formulation of it. We then continue by designing an HRS device using a single electrical rotational motor and mechanical means to replicate the walking gait of a horse, then tune it to an extent to replicate a human walking gait. To measure the performance of our design, we compare the gait of the user when riding our device versus walking.

Human induced pluripotent stem cell (iPSC)-based model systems can be used to produce blood cells for the study of both hematologic and non-hematologic disorders. This commentary discusses recent advances that have utilized iPSC-derived red blood cells, megakaryocytes, myeloid cells, and lymphoid cells to model hematopoietic disorders. In addition, we review recent studies that have defined how microglial cells differentiated from iPSC-derived monocytes impact neurodegenerative disease. Related translational insights highlight the utility of iPSC models for studying pathologic anemia, bleeding, thrombosis, autoimmunity, immunodeficiency, blood cancers, and neurodegenerative disease such as Alzheimer’s.

The individual and combined effects of extracellular products (ECP) from Arthrobotrys oligospora (Ao) and A. musiformis (Am) growth in liquid media against Haemonchus contortus L3 (HcL3) were assessed. The following methodological steps were established: isolation, morphological (MI) and molecular identification (Mol-I), assessment of nematocidal activity (NA) of fungal liq-uid culture filtrates (LCF) produced in two liquid media alone and in combination and finally, the myco-compound profile identification (MCP). The MI of both isolates suggested that the fungi corresponded to the species Ao and Am. This result was confirmed by PCR analysis followed by sequencing, alignment and obtaining coverage and similarity with respect to isolates reported in the NCBI database. Likewise, the highest Hc mortalities were 91.4% with individual LCF of Am and 86.2% with those of Ao at the highest concentration (100 mg/mL) in Czapek-Dox Broth. The combination of both LCF resulted in a similarly high larval mortality with no statistical differ-ences in relation to individual activity (P>0.05). The MCP showed the presence of alkaloids in both fungi. Coumarins, triterpenes and saponins were found only in Ao. Both fungi produced ECP with a high NA that could be identified and assessed in future studies as potential natural an-thelmintic compounds.

This study aimed to examine the physical response of international referees, participating in different levels of world competitions for footballers with cerebral palsy (CP). Thirteen international referees, who officiated 49 matches in the men’s 2022 World Cup (1st to 15th ranked teams) and 2022 World Championships (16th to 30th ranked teams), participated in this study. A cross-sectional design was used to determine the physical responses and compare the 1st and 2nd halves and the performance in the different tournaments, recording physical variables throughout the matches. Significant higher physical responses (p &lt; 0.05; d = 0.50-0.93; moderate to large) were observed in the World Cup in comparison to the World Championship. Overall, high-level tournaments have been shown to elicit more intense physical responses from referees officiating CP football matches compared to lower-level tournaments. For the World Cup, significantly higher number of accelerations (p = 0.01; d = -0.55; moderate) and decelerations (p &lt; 0.01; d = -0.54; moderate) were registered in the 1st half compared to the 2nd half. This information may be useful for the strength and conditioning coaches of referees to plan weekly training sessions more specifically and adjust the periodical training load and post-match recovery protocols.

The purpose of this study was to quantify characteristics of bimanual movement intensity during 30-hour Hand Arm Bimanual Intensive Therapy (HABIT) and bimanual performance (activities and participation) in real-world using accelerometers in children with unilateral cerebral palsy (UCP). Twenty-five children with UCP participated in a 30-hour HABIT program. Data was collected from bilateral wrist-worn accelerometers during 30-hours HABIT to quantify the movement intensity, and three days pre- and post-HABIT to assess real-world performance gains. Movement intensity and performance gains were measured using six standard accelerometer-derived variables. Bimanual capacity (body function and activities) was assessed using standardized hand function tests. We found that accelerometer variables increased significantly during HABIT, indicating increased bimanual symmetry and intensity. Post-HABIT, children demonstrated significant improvements in all accelerometer metrics, reflecting real-world performance gains. Children also achieved significant and clinically relevant changes in the hand capacity following HABIT. Therefore, our findings suggest that accelerometers can objectively quantify bimanual movement intensity during HABIT. Moreover, HABIT enhances hand function as well as activities and participation in real-world situation in children with UCP.

The development of 3D cerebral brain organoids which accurately resemble aspects of the human brain permits a more accurate characterization of physiological processes and neurological diseases. Cerebral organoids can be grown from stem cell lines with various genetic backgrounds allowing multiple neurodegenerative diseases to be modeled. While dysfunction in neurotransmission of patients with neurodegenerative diseases is expected, the impact of chronic neurodegeneration on the response to viral infection of the CNS is poorly understood. For instance, several mosquito-borne viruses like Dengue virus and West Nile Virus cause post-viral parkinsonism. How CNS infection might impact a host with inherent CNS dysfunction such as Parkinson’s Disease in poorly understood. This preliminary, observational study aimed to understand dysfunction in intrinsic and innate expression of a patient with a neurodegenerative disease and a non-affected individual in relation to potential viral infection in the CNS. Cerebral organoids were generated from human induced pluripotent stem cells with a normal genetic background or with idiopathic Parkinson’s Disease. After differentiation and maturation, organoid size, gene expression and immunofluorescence were evaluated to assess neurotransmission and innate immunity. While there was no significant difference in size of the organoids with a normal or Parkinson’s genetic background, gene expression studies identified multiple differences in innate immunity and neurotransmission. Immunofluorescence also identified differences in protein expression related to neurotransmission and innate immunity. Of note, organoids derived from a Parkinson’s patient exhibited endogenous up-regulation of dopamine and muscarinic acetylcholine receptors, GABA, glycine, and glutamate targets, and the majority of cytokines. This expression pattern suggests a chronic state of neuroexcitation and neuroinflammation in this population of organoids.

In this work, we proposed a novel design of microfluidic mixer utilizing the amplified Marangoni chaotic advection induced by AC continuous electrowetting of a metal droplet situated in electrolyte solution, due to the linear and quadratic voltage-dependence of flow velocity at small or large voltages, respectively. Unlike previous researchers exploiting the unidirectional surface stress with DC bias at droplet/medium interface for pumping of electrolyte where the resulting flow rate is linearly proportional to the field intensity, dominance of another kind of dipolar flow pattern caused by local Marangoni stress at the drop surface in sufficiently intense AC electric field is demonstrated by both theoretical analysis and experimental observation, which exhibits a quadratic growth trend as a function of the applied voltage. The dipolar shear stress merely appears at larger voltages and greatly enhances the mixing performance by inducing chaotic advection between the neighboring laminar flow. The mixer design developed herein, on the basis of amplified Marangoni chaotic advection around a liquid metal droplet at larger AC voltages, has great potential for chemical reaction and MEMS actuator applications, because of generating high-throughput and excellent mixing performance at the same time.

Blood gas analysis plays a central role in modern medicine. Advances in technology have expanded the range of available parameters and increased the complexity of their interpretation. By applying user-centered design principles, it is possible to reduce the cognitive load associated with interpreting blood gas analysis. In this international, multicenter study, we explored anesthesiologists' perspectives on Visual Blood, a novel visualization technique for presenting blood gas analysis results. We conducted interviews with participants following two computer-based simulation studies: the first utilizing Virtual Reality (VR) (50 participants) and the second without VR (70 participants). Employing the template approach, we identified key themes in the interview responses and formulated six statements, which were rated using Likert scales: from 1 (strongly disagree) to 5 (strongly agree) in an online questionnaire. The most frequently mentioned theme was the positive usability features of Visual Blood. The online survey revealed that participants found Visual Blood to be an intuitive method for interpreting blood gas analysis (median 4, IQR 4-4, p<0.001). Participants noted that minimal training was required to effectively learn how to interpret Visual Blood (median 4, IQR 4-4, p<0.001). However, adjustments are necessary to reduce visual overload (median 4, IQR 2-4, p<0.001). Overall, Visual Blood received a favorable response. The strengths and weaknesses derived from these data will help optimize future versions of Visual Blood to improve the presentation of blood gas analysis results.

In this paper, we aim to present real implementation cases where non-visible elements of environmental impact assessments (EIA), wind flow, are visualized using a 3D digital twin technology. The conventional EIA process serves as a crucial tool in the evaluation of potential environmental impacts prior to the initiation of development projects. This evaluation helps to establish a legal and institutional framework that seeks to minimize the adverse effects on the environment. However, traditional EIA methods present challenges, particularly for non-experts, in comprehending the results of assessments involving non-visible environmental factors such as noise, air quality, and wind flow. These elements are often represented in static images or numerical tables, limiting accurate understanding and engagement. Our proposed method, termed Digital Twin based EIA, addresses these limitations by leveraging digital twin technology. This advanced methodology allows for the visualization of non-visible environmental elements in a spatio-temporal dimension, providing a more interactive and comprehensive user interface/experience for both citizens and stakeholders. In this context, we present a unique case study that focuses on visualizing wind flow using this technology. This paper serves as an example of how digital twin platforms can enhance traditional EIA processes, offering a more immersive and informative experience. The evolution of EIA into the digital realm signifies an important step forward in fostering public understanding and engagement in environmental protection efforts.

The pressure exerted on the heart and blood vessels because of blood flow is considered as an important parameter for the cardiovascular function. It determines sufficient blood perfusion as well as transportation of nutrition, oxygen and other essential factors to every organ. Pressure in the primary arteries located near the heart and the brain, known as central blood pressure (CBP), while in peripheral arteries, known as peripheral blood pressure (PBP). Normally, CBP and PBP are correlated; however, cardiovascular disorders interfere their regulation and affect the blood flow in vital organs and accessory organs, differently. Therefore, understanding each of them in normal and disease conditions is essential for managing various cardiovascular disorders and increasing their treatment outcomes. In this review, we have described the control systems (neural, hormonal, osmotic and cellular) of the blood pressure and its regulation in hypovolemic shock using centhaquine (Lyfaquin®) as a resuscitative agent.

Backgrounds Linear association has widely been assumed for prediction of aging-related fractional anisotropy (FA) decline in white matter of the brain. While useful for testing significance of the aging effect, it fails to identify a threshold age before and after which the age-FA association changes. Identification of such a threshold is often of clinical interest for timely intervention. Methods We employed a sigmoidal growth function to test a threshold effect in age triggering onset of cerebral decline in 21 white matter tracts, and compared its fitting performance to those of linear, and power regression. The study sample was a normal healthy cohort of 106 participants with ages in mid-life ranging from 18 to 60 years. Results Of the 21 white matter tracts analyzed, the posterior thalamic radiation showed better fit with sigmoidal curve model, compared to a linear or power regression. The estimated threshold age in years (95% confidence interval) were 47.2 (44.1-48.4). Conclusion While available evidence regarding the presence of a specific age threshold for cerebral decline in mid-life based on FA was limited, the posterior thalamic radiation exhibited a threshold age of 47.2. Beyond this age point, we observed a significant change in the FA risk pattern.

Introduction: Adverse events related to vaccines are reactions that can lead to serious complications, in the present that we live at the publication of this article with the need to generate high rates of vaccination have been presented in the case of vaccine agents against COVID-19 adverse events, with thrombotic events being the most important. Case Presentation: This is a 37-year-old female patient who presents 11 days after ChAdOx1-S vaccination against COVID-19 presents with intense headache associated with symptoms of intracranial hypertension, she was initially taken to simple cranial tomography showing presence of cerebral edema and indirect signs of cerebral venous thrombosis, it is proposed to carry out cerebral angiography which showed the presence of thrombosis of both transverse venous sinuses, no hypercoagulability states were found in the laboratories, the immunological tests carried out for antiphospholipid syndrome were negative, the thrombotic event was associated with the ChAdOx1-S vaccine, later the patient was taken to thrombectomy by Neuroradiology, achieving complete channeling of both transverse venous sinuses. Conclusions: Adverse events associated with vaccination have been described with multiple vaccine agents, this component against COVID-19 is also an event to consider, knowing the pathophysiology of these events is essential to be able to reduce these risks and select the least risky agent. Despite this risk, vaccination remains the only cost-effective measure to reduce the morbidity and mortality associated with COVID-19.

Only cross-sectional studies have demonstrated muscle deficits in children with spastic cerebral palsy (SCP). The impact of functional impairments on altered muscle growth remains unclear. This prospective longitudinal study modelled the morphological muscle growth in 87 children with SCP (age range 6 months to 11 years, Gross Motor Function Classification System [GMFCS] level I/II/III=47/22/18). Repeated ultrasound assessments were performed during 2-year (y) follow-up with an interval of minimal 6 months. Three-dimensional freehand ultrasound was applied to assess medial gastrocnemius muscle volume (MV), mid-belly cross-sectional area (CSA) and muscle belly length (ML). Non-linear mixed models compared trajectories of (normalized) muscle growth between GMFCS-I versus GMFCS-II&amp;III. MV and CSA growth trajectories showed piecewise model with 2 breakpoints, with the highest growth before 2y and negative growth rates after 6-9y. Before 2y, children with GMFCS-II&amp;III already showed lower growth rates compared to GMFCS-I. From 2-9y, the growth rates did not differ between GMFCS-levels. After 9y, a more pronounced reduction in normalized CSA was observed in GMFCS-II&amp;III. Different trajectories in ML growth were shown between the GMFCS-level subgroups. These longitudinal trajectories could be used to monitor the SCP muscle pathology during childhood and to optimize treatment planning and goals aiming to stimulate muscle growth

The COVID-19 pandemic has caused unprecedented challenges in the care of children with cerebral palsy (CP) and other neuromuscular complex chronic conditions (NCCC). The purpose of this study was to explore the direct impact of the COVID-19 pandemic on healthcare delivery. From May to August 2020, medical professionals caring for CP and NCCC patients across multiple countries and disciplines completed a self-administered cross-sectional survey comparing practices before and during the COVID-19 pandemic. Of the 79 healthcare workers from 8 countries who participated—predominantly pediatric orthopedic surgeons (32%), pediatricians (30%), and pediatric physiatrists (23%)—most felt that caring for NCCC patients during the pandemic presented with unique difficulties and reported a significant decrease in in-person NCCC clinic volume (p<0.001), multidisciplinary appointments (p<0.001), surgical cases (p=0.005), and botulinum toxin/phenol injections. Most providers affirmed that institutional guidelines for perioperative emergent/urgent and elective procedures, workplace settings, and technology were modified to accommodate the ongoing public health crisis. Usage of telemedicine significantly increased for NCCC patient visits (p<0.001). During the COVID-19 pandemic, many children with NCCC lost access to routine, multidisciplinary care. Telemedicine became an integral part of communication and management. In the setting of the COVID-19 pandemic and threat of future healthcare disruptions, these data lay the foundation for trending the evolution of healthcare delivery and accelerating best practice guidelines for children with CP and NCCC.

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

Unsteady flow is the most common and complicated form of fluid motion in nature. This paper takes the beaches of key waterways in the middle and lower reaches of the Yangtze River as the research object, analyzes the water surface distribution and average flow velocity distribution near the beach, and analyzes the differences. The relationship between the flow pattern of the steep slope and the water flow pattern of the entire survey area and the steep slope of the beach and its nearby water flow structure. The water flow near the beach is divided into four major blocks: the swelling water area, the falling water area, the backwater area and the maximum flow rate area. The water flow structure characteristics and the cause of each block are analyzed.

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

Recanalization poses challenge in coil embolization for cerebral aneurysms. Establishing predictive models for post-embolization recanalization is important for clinical decision-making. However, conventional statistical and machine learning (ML) models may overlook critical parameters during the initial selection process. In this study, we automated the identification of significant hemodynamic parameters using a PointNet-based deep neural network (DNN), leveraging their inherent 3D features. Further feature analysis was conducted utilizing saliency mapping, an explainable artificial intelligence (XAI) technique. The study encompassed the analysis of velocity, pressure, and wall shear stress (WSS) in both pre- and post-coiling models derived from computational fluid dynamic (CFD) simulations for 59 aneurysms. Velocity was identified as the most pivotal parameter, supported by the lowest P-value from statistical analysis and the highest area under the curves (AUROC)/precision-recall curves (AUPRC) values from DNN model. Moreover, visual XAI analysis revealed robust injection flow zones with notable impingement points in pre-coiling models, as well as pronounced interplay between flow dynamics and the coiling plane were important 3D features in identifying the recanalized aneurysms. The combination of DNN and XAI was found to be an accurate and explainable approach not only at predicting post-embolization recanalization but also at discovering unknown features in the future.

The pathogenesis of Cerebral Small Vessel Disease (CSVD) is largely unknown. Endothelial disfunction has been suggested as the turning point in CSVD development. In this study we tested the effect of plasma from CSVD patients on human cerebral microvascular endothelial cells with the aim of describing the pattern of endothelial activation. Plasma samples from 3 groups of young subjects have been tested: PTs (subjects affected by early stage CSVD); CTRLs (control subjects without abnormalities at MRI scanning); BDs (blood donors). Human Brain Endothelial Cells 5i (HBEC5i) were treated with plasma and total RNA was extracted. RNAs were pooled to reduce gene expression-based variability and NGS analysis was performed. Differentially expressed genes were highlighted comparing PTs, CTRLs and BDs with HBEC5i untreated cells. No significantly altered pathway was evaluated in BD related treatment. Regulation of p38 MAPK cascade (GO:1900744) was the solely pathway altered in CTRLs related treatment. Indeed, 36 different biological processes turned out to be deregulated after PTs treatment of HBEC5i, i.e., the cytokine-mediated signaling pathway (GO:0019221). Endothelial cells activate inflammatory pathways in response to stimuli from CSVD patients’ plasma, suggesting the pathogenetic role of neuroinflammation from the early asymptomatic phases of cerebrovascular disease.

Investigations are currently in progress to assess the potential of elevated FABP3 levels as biomarkers for assessing cardiac and cerebral injury post-stroke. Ongoing research endeavors are concentrated on elucidating the specific mechanisms by which FABPs, particularly FABP3, contribute to the complex processes involved in ischemic stroke. This study employs molecular docking techniques within a Virtual Screening framework to examine the interaction between various natural substances and the active site of human heart fatty acid-binding protein (PDB Code 4TKH). Utilizing Pyrx and Autodock Vina, the research aims to pinpoint compounds demonstrating robust binding interactions, characterized by high binding energy scores (kcal/mol) and the formation of multiple chemical bonds. The anticipated outcomes have the potential to yield valuable insights into the molecular interactions influencing human heart fatty acid-binding protein, suggesting possible implications for therapeutic interventions using these natural substances.From the docking and predicted toxicity results, Resistomycin has demonstrated superior characteristics compared to Morusin.

This study focuses on traffic condition analysis, especially in under developing country India and makes more visible of traffic flow by using traffic flow theory in order to understand real traffic condition. India is one of rapid economic growing countries and large market with second largest population 1.3 billion in 2018. On the other hand, there are social issues such as environment air pollution and global warming by traffic CO2 emission of transportation. This kind of condition is not only in India, but in other South East Asia and Africa in future. From recent more than one-month traffic observation in a typical major city Ahmedabad in Gujarat state, which has about 8 million population and industrialized city. In terms of traffic data collection, 14 CCTV cameras are used in the city. Based on multiple traffic cameras monitoring, author found the unique traffic flow characteristics and compares traffic flow theory. In this study, it is described what is key parameters to show real traffic congestion condition and how these congestion occurs.

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

Polymer flooding is one of the most successful chemical EOR methods, and is primarily implemented to accelerate oil production by sweep improvement. However, other benefits have extended the utility of polymers. During the last decade, it has been evaluated for an increasing number of fields, both offshore and onshore. This is a consequence of improved polymer properties, which extends the use to HTHS (high temperature high salinity) conditions and of improved understanding of flow mechanisms such as for heavy oil mobilization. A key issue in understanding polymer performance is to control and predict in-situ porous medium rheology. The first part of this paper reviews recent developments in understanding polymer flow in porous medium. Especially, polymer in-situ rheology and injectivity is discussed. The second part of this paper reports polymer flow experiments using the most applied polymer for EOR processes, HPAM (partially hydrolyzed polyacrylamide). The experiments address high rate near-wellbore behavior (radial flow) as well as reservoir rate steady state flow (linear flow) and discuss differences observed in terms of flow conditions. In addition, impact of oil on polymer rheology was investigated, and compared to single-phase polymer flow in Bentheimer sandstone rock material. Presence of oil leads to a reduction in apparent viscosity.

Imaging flow cytometry (ImFC) represents a significant technological advancement in the field of cytometry, effectively merging the high-throughput capabilities of flow analysis with the image-based features of microscopy. In this comprehensive review article, we take a historical perspective and delve into the evolution of this methodology, presenting its past, exploring current state-of-the-art and forecasting potential future advancements. The inception of ImFC arose from the innovative combination of a flow cytometer's hydraulics with the technology of an advanced camera. This synergistic coupling facilitated the morphological analysis of cell populations at a high-throughput scale, effectively evolving the landscape of cytometry. However, the application of ImFC faced several challenges. Among the most prominent ones, is the development and implementation of software systems that can reliably and efficiently handle the robust data acquisition and analysis inherent in ImFC. The scale and complexity of the data generated by ImFC necessitates the creation of novel analytical tools that can effectively manage and interpret this data, thus allowing us to unlock the full potential of ImFC. Interestingly, artificial intelligence (AI) algorithms have begun to be implemented on ImFC, offering a promise for enhancing analytical capabilities. The adaptability and learning capacity of AI may prove to be essential in knowledge mining from high-dimensional data produced by ImFC, potentially enabling more accurate analyses. Looking forward, we project that ImFC may become an indispensable tool, not only in research laboratories but also in clinical settings. Given the unique combination of high-throughput cytometry and detailed imaging offered by ImFC, we foresee a critical role for this technology in the next generation of scientific research and diagnostics. As such, we encourage both current and future scientists to consider the integration of ImFC as an addition to their research toolkit and clinical diagnostic routine.

Oxidative stress has been implicated in cellular senescence and aging, as well as in the onset and progression of many diverse genetic and acquired diseases and conditions. The search for biomarkers of oxidative stress has become relevant to many biomedical fields using many different methods and approaches. Fluorescence methodology is advantageous because of its simplicity and high sensitivity. Fluorescent probes are frequently used to investigate the role of reactive oxygen species in oxidative stress in experimental or clinical settings, often involving the use of flow cytometry and related single-cell based technologies. To assess the specific role of reactive oxygen species in oxidative stress studies by cytometric methodologies, it is essential to detect and characterize these species accurately. However, the detection and quantitation of individual intracellular ROS is still a challenge, but different and complementary strategies may focus on other endpoints of oxidative stress. In this review we present and discuss briefly the limitations and perspectives of such approaches. Based on our results, we also provide recommendations for proper design of cytometric studies of oxidative stress in order to prevent or minimize experimental errors..

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

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

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.

The adoption of Pump as Turbines (PATs) both in small scale hydroelectric plants and water supply systems has brought different advantages, the most recognized being cost-effectiveness as compared to other hydroturbines. However, due to their lack of flow control ability, their intolerance to off-design operations constitutes one tough shortfall. Moreover, this technology’s newness leads to PAT flow dynamics still being ununderstood even to date. Therefore, this study intends to numerically investigate the mixed flow PAT’s pump mode flow dynamics for five operating conditions expanding from optimum (1QBEP) to deep part-load (0.41 QBEP) conditions. Moreover the effect of runner blade angle on the same has been investigated where three angles namely -2°, 0°, and 2° have been considered. PAT flow stability was found to deteriorate as the flow decreased, where associated pressure pulsation level worsened at different flow zones. In addition, the blade angle increase led correspondingly increasing flow unsteadiness and pressure pulsation levels, where the pulsation frequencies from rotor-stator interactions were dominant for most of flow zones. This study’s findings are of a crucial importance to both scientific and engineering communities as they contribute to thorough understanding of PAT flow dynamics.

We evaluated the association of blood pressure with blood levels of cadmium, lead, and cadmium and lead together (cadmium+lead) in a representative sample of adolescents from Korea by use of 2010-2016 data from the Korean National Health and Nutrition Examination Survey (KNHANES). This cross-sectional study enrolled adolescents aged at 10-18 years-old who completed a health examination survey and had blood measurements of lead and cadmium. The association of adjusted mean differences in diastolic and systolic blood pressure with doubling of blood lead and cadmium were estimated by regression of blood pressure against log₂-transformed blood metals and their quartiles after covariate adjustment. Adjusted odds ratios for prehypertension were calculated for log₂-transformed blood levels of lead and cadmium and their quartiles. Our analysis of adolescents in Korea indicated that blood levels of lead and cadmium were not significantly associated with increased blood pressure or risk of pre-hypertension. However, the cadmium+lead level was associated with pre-hypertension. Previous studies showed that blood levels of lead and cadmium were associated with increased blood pressure and risk of hypertension in adult populations. We found no such effect in Korean adolescents, although the cadmium+lead level was associated with prehypertension. These differences may be because adolescents generally have lower levels of these blood metals or because adolescents only rarely have hypertension.

This study aimed to evaluate the early-childhood comorbidities of cerebral palsy (CP) in children with low birth weight (LBW) and assess the impact of maternal bio-psychosocial factors on the risk of CP in preterm infants across varying birth weights. Data for 15,181 prematurely born infants from 2009 to 2013 and 151,810 matched controls from Taiwan's National Health Insurance Research Database were analyzed. Period prevalence of CP, and comorbidities of LBW were verified, and odds ratios (ORs) were calculated. Results confirmed that increasing prematurity and low birth weight (LBW) rates in Taiwan. LBW was associated with higher CP prevalence. Maternal age extremes (&lt;20 and &gt;40 years) were significant risk factors of CP in LBW infants. LBW infants showed higher risks of respiratory, circulatory, and nervous system and psycho-developmental comorbidities compared to controls. Infants with the lowest birth weights had even higher ORs for these comorbidities. However, gastrointestinal and nutritional comorbidities were less prevalent in premature infants. Maternal factors such as family income, number of hospital admissions, and length of hospital stay were significantly correlated with birth weight and subsequent complications. Each additional gestational week significantly reduced the risk of complications in premature infants. Additionally, maternal bio-psychosocial factors were associated with birth weight and related outcomes in premature infants, emphasizing the importance of addressing these factors in prenatal care and interventions.

This study centers on childcare facilities catering to children with moderate cerebral palsy, exploring a four-phase process: (1) cultivating an understanding and acceptance, (2) integrating specialized resources, (3) developing strategic plans, and (4) establishing stable collaboration. The case study demonstrates the profound impact of well-rounded support systems. Children with cerebral palsy showed marked improvements in development and emotional stability. Concurrently, their peers developed greater empathy and cooperative skills, smoothly adjusting to the inclusive setting. Additionally, the childcare staff refined their methods and attitudes, enhancing their ability to meet each child's specific needs and thus elevating the standard of integrated care.Concluding with three strategic recommendations, the paper proposes measures to augment the quality of care for children with special needs. These include defining clearer guidelines and policies for special needs care in childcare environments, emphasizing professional development and the amalgamation of diverse resources to cultivate a more skilled caregiving workforce, and encouraging robust partnerships between parents and childcare facilities. These recommendations are expected to significantly influence the domain of inclusive education, providing crucial insights for those engaged in early childhood care and education..

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

Pregnancy at advanced maternal age is considered a risk factor for adverse maternal, fetal, and neonatal outcomes. Here we investigated whether maternal age could be associated with differences in the blood levels of newborn screening (NBS) markers for inborn metabolic disorders on the Recommended Universal Screening Panel (RUSP). Population-level NBS data from screen-negative singleton infants were examined, which included blood metabolic markers and covariates such as gestational age, birth weight, age at blood collection, infant sex, parent-reported ethnicity, and maternal age at delivery. Marker levels were compared between maternal age groups (age range: 15-44 years) using effect size analyses, which controlled for group size differences and potential confounding from other covariates. Our results showed that 13% of the markers had maternal age-related differences including newborn metabolites with either increased (C14, C16, C18, C18:1, C3DC) or decreased (C5OH) levels at advanced maternal age group (≥35 years, absolute Cohen’s d ≥ 0.2). The increased C3DC levels in this group correlated with a higher false-positive rate in newborn screening for malonic acidemia (p-value < 0.001), while no significant difference in screening performance was seen for other markers. Maternal age at delivery is associated with inborn metabolic differences and should be considered together with other clinical variables in genetic disease screening.

The giant panda (Ailuropoda melanoleuca) is one of the most endangered species of land mammals and has significant academic research value worldwide. The evaluation of hematological parameters in giant pandas is important for assessing the physiological status of animals. This study collected blood samples from 12 healthy giant pandas from September 2018 to August 2020 under non-anesthetic conditions. The samples were then analyzed for basic blood indices and blood rheology, and normal values for hematological parameters and blood rheology under non-anesthetic conditions in giant pandas in Beijing area were obtained. The study confirmed the influence of age and season on hematological and biochemical parameters in captive giant pandas: hematological morphology, blood rheology, and serum enzymes showed seasonal variations, while age affected the changes in serum enzymes, serum protein content, and serum metabolite content. There are significant differences in blood indicators among different age groups of giant pandas, indicating variations in the overall metabolic processes and differences among pandas of different age groups. Seasonal variations showed a regulatory effect on blood rheology parameters and a negative effect on blood viscosity. Further research should be conducted to investigate whether factors such as season and climate cause environmental stress in captive giant pandas. The results obtained in this study aim to better protect the stability of the giant panda population and provide references for the appropriate feeding and medical care of captive giant pandas.

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.

Blood cell analysis is a crucial diagnostic process in medical practice. In particular, detecting white blood cells (WBCs) is essential for diagnosing of many diseases. The manual screening of blood films is a time-consuming and subjective process, which can lead to inconsistencies and errors. Therefore, automated detection of blood cells can improve the accuracy and efficiency of the screening process. In this study, an explainable Vision Transformer (ViT) model was proposed for the automatic detection of WBCs from blood films. The proposed model utilizes the self-attention mechanism to extract relevant features from the input images and leverages transfer learning by incorporating pre-trained model weights to improve its performance. The proposed model achieved a classification accuracy of 99.40% for five distinct types of WBCs and exhibited potential in reducing the time required for manual screening of blood films by pathologists. Upon examination of the misclassified test samples, it was observed that incorrect predictions were correlated with the presence or absence of granules in the cell samples. To validate this observation, the dataset was divided into two classes, namely Granulocytes and Agranulocytes, and a secondary training process was conducted. The resulting ViT model trained for binary classification achieved an accuracy of 99.70%, recall of 99.54%, precision of 99.32%, and F-1 score of 99.43% during the test phase. To ensure the reliability of the ViT model's multi-class classification of WBCs, the pixel areas that the model focuses on in its predictions are visualized through the Score-CAM algorithm.

Background of the Study: We investigated the link between hypertension and cancer since it has been suggested that hypertension may raise the long-term risk of cancer. Previous large observational cohort studies found that greater blood pressure (BP) was related to a higher risk of cancer. Mendelian randomization (MR) was utilized to produce less confounded blood pressure estimates (BP) on overall and site-specific malignancies. The study aims to draw conclusions on the relationship between high blood pressure and cancer. Methods: Studies on high blood pressure and various malignancies are inconclusive, except for renal cell carcinoma. However, given that most meta-analyses only contained a limited number of trials, some relative risks had small to moderate magnitudes, and several may have been impacted by residual confounding, careful interpretation is necessary. The study was conducted using the meta-analysis technique. Cochran's Q test and I2 test were used to assess statistical heterogeneity between studies in the current investigation for research involving two or more cause and outcome combinations. Results: Positive correlations were also reported between high blood pressure and esophageal adenocarcinoma, squamous cell carcinoma, liver, and squamous cell carcinoma. However, most studies lacked multivariable adjustments. Physical and numerical risk of cardiovascular disease is linked to bowel cancer but no other cancers. According to a meta-analysis, hypertensive persons could also be at increased danger of gastrointestinal and breast cancer. Most meta-analyses comprised several trials with moderate or mild hazard ratios.ConclusionDifferent types of cancers have been noted to be directly caused by hypertension. In addition, some treatments have also been associated with the side effects of cancer treatments to cause hypertension. Women facing hypertension have an increased risk of getting breast cancer. Although some cancers showed a real relationship with hypertension, others had no connection at all.

After the first weeks of vaccination against the SARS-CoV-2, several cases of acute thrombosis were reported. These news reports began to be shared frequently across social media platforms. The aim of this study was to conduct an analysis of Twitter data related to the overall discussion. Data was retrieved from 14th March to 14th April using the keyword ‘blood clots’. A dataset with n=266,677 tweets was retrieved, and a systematic random sample of 5% of tweets (n=13,334) were entered into NodeXL for further analysis. Social network analysis was used to analyse the data by drawing upon the Clauset-Newman-Moore algorithm. Influential users were identified by drawing upon the betweenness centrality metric. Text analysis was applied to identify the key hashtags and websites used at this time. More than half of the network was comprised of retweets and the largest groups within the network were broadcast clusters where a number of key users were retweeted. The most popular narratives were around highlighting the low risk of obtaining a blood clot from a vaccine and highlighting higher blood clot risks in medicines commonly consumed. A wide-variety of actors drove the discussion on Twitter ranging from writers, physicians, the general public academics, celebrities, and journalists. Twitter was used to highlight the low potential of obtaining a blood clot from a vaccine and encouraged vaccinations among the public.

Blood-brain-barrier is a major obstacle in treating brain-related disorders as it does not allow to deliver drugs in the brain. In order to facilitate delivery of drugs in brain, we developed a method for predicting blood-brain-barrier penetrating peptides. These blood-brain barriers penetrating peptides (B3PPs) can act as therapeutic as well as drug delivery agents. We trained, tested, and evaluated our models on blood-brain-barrier peptides obtained from the B3Pdb database. First, we compute a wide range of peptide features then we select relevant peptide features. Finally, we developed numerous machine learning-based models for predicting blood-brain-barrier peptides using selected features. Our model based on random forest performed best on the top 80 selected features and achieved a maximum 85.08% accuracy with 0.93 AUROC. We also developed a web server, B3pred that implements our best models. It has three major modules that allow users to; i) predict B3PPs, ii) scanning B3PPs in a protein sequence, and iii) designing B3PPs using analogs. Our web server and standalone software is freely available at https://webs.iiitd.edu.in/raghava/b3pred/.

Since its introduction almost 50 years ago, the concept of ‘flow’ has been descriptive of optimal experiences, also in relation to play. However, the explorative nature of play leads to some discrepancies between flow and the optimal experience of play. In this paper the differences between flow and play are explored, leading to proposing the state of ‘wonder’ (directed at exploration) as an alternative to ‘flow’. From this perspective, the study further explores how we may design toys that enable meaningful experiences of play, identifying opportunities in designing for toys as the enablers of immersed experiences of wonder.

This paper presents some results from a computational fluid dynamics (CFD) model of a multi-megawatt crosswind kite spinning on a circular path in a straight downwind configuration. The unsteady Reynolds averaged Navier-Stokes equations closed by the k−ω SST turbulence model are solved in the three-dimensional space using ANSYS Fluent. The flow behaviour is examined at the rotation plane, and the overall (or global) induction factor is obtained by getting the weighted average of induction factors on multiple annuli over the swept area. The wake flow behaviour is also discussed in some details using velocity and pressure contour plots. In addition to the CFD model, an analytical model for calculating the average flow velocity and radii of the annular wake downstream of the kite is developed. The model is formulated based on the widely-used Jensen’s model (Technical Report Risø-M; No. 2411, 1983), which was developed for conventional wind turbines, and thus has a simple form. Expressions for the dimensionless wake flow velocity and wake radii are obtained by assuming self-similarity of flow velocity and linear wake expansion. Comparisons are made between numerical results from the analytical model and those from the CFD simulation. The level of agreement was found to be reasonably good. Such computational and analytical models are indispensable for kite farm layout design and optimization, where aerodynamic interactions between kites should be considered.

In this study, the author proposes to evaluate the effect of sales growth, Receivable Turnover and operating cash flow on the liquidity of PT. Unilever Indonesia Plc. The research method used is descriptive method with a quantitative approach. In this statement, the population used in this study is the financial statement data from PT. Unilever Indonesia Plc. from 2010 to 2018, the technique of determining the sampling uses Purposive Sampling. This research data uses secondary data from PT. Unilever Indonesia Plc financial statements from 2010 to 2018. All data sources were obtained from the website of the Indonesia Stock Exchange at https://www.idx.co.id, the company's website and Google search. Our analysis reveals that sales growth and accounts receivable turnover from PT. Unilever Indonesia Plc. has no influence on the liquidity of PT. Unilever Indonesia Plc, while operating cash flow has an influence on the Liquidity of PT Unilever Indonesia Plc. This means the ups and downs of the value of sales and accounts receivable turnover of a company has no influence on the liquidity of PT. Unilever Indonesia Plc, while operating cash flow has increased or decreased has an influence on the liquidity of PT Unilever Indonesia Plc. The value of sales growth, accounts receivable turnover and operating cash flow can explain the liquidity of PT Unilever Indonesia Plc. by 78%, while 22% is explained by other factors which are not included in this study.

The study focused on two climatic variables i.e. precipitation and stream flow for analysing change in trend of rainfall for the River Ssezibwa Catchment area and stream flow of River Ssezibwa. This Catchment is found in the districts of Mukono and Buikwe in Uganda. In this area agriculture is majorly dependent on rainfall and irrigation on a small scale. However, rainfall occurrence has become unpredictable over the past few years as result of the changes in patterns of weather. This has caused severe effects on the agricultural cropping system as well as caused negative effects on the natural water resources. Stream flow data of 57 years (1960 – 2017) and rainfall data for 35 years (1982 – 2017) on a daily basis was analysed to find out the trend and detect change point. Trend analysis was done by using the non-parametric analysis while the change point detection was carried out by using the Pettit test (1979).Magnitude of trend for the time series data was carried out using Sen’s Slope estimator and Mann – Kendall test was done to determine the trend. Results from the statistical analysis highlighted that; for stream flow the trend was generally positive and change point detected to be in the year 2000 while for rainfall data analysis indicated that the trend was predominantly negative and change point was in the year 1998.

In Shark Bay, a large hypersaline bay in Western Australia, longitudinal density gradients force gravitational circulation that is important for Bay-ocean exchange. Observations of vertical stratification and velocity are presented, confirming a steady near-bed dense water outflow from Shark Bay’s northern Geographe Channel that persisted through all stages of the tide. Outflow velocities were 2–3 times stronger than the outflows recorded previously in Naturaliste Channel (in the west) and were more resistant to breakdown by tidal mixing. Estimates of turbulent kinetic energy production derived from ADCP data using the variance method showed a more complex structure in Geographe Channel, due to shear associated with the stratified conditions, with peak levels of turbulence occurring during reversal of tidal flows. For both channels the main source of turbulence was tidal flow along the seabed, with the bottom current speed cubed, |U_b³|, providing a reasonable proxy for tidal mixing and prediction of dense water outflows from Shark Bay the majority of the time. Orientation and deeper water of Geographe Channel along the main axis of the longitudinal density gradient provided an explanation for the predominant outflow from the Bay’s northern entrance. These density-driven currents could potentially influence recruitment of commercially fished scallops and prawns through dispersal and flushing of larvae.

A techno-economic model was developed to investigate the influence of components on the system costs of redox flow batteries. Sensitivity analyses were carried out based on a example of a 10 kW/120 kWh vanadium redox flow battery system and the costs of the individual components were analyzed. Particular consideration was given to the influence of material costs and resistances of bipolar plates and energy storage media as well as voltages and electric currents. Based on the developed model it was possible to formulate statements about the targeted optimization of existing battery systems and general aspects for future developments of redox flow batteries.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists throughout the world with over 65 million registered cases of survivors with post-COVID-19 sequelae, also known as LongCOVID-19 (LongC). LongC survivors exhibit various symptoms that span multiple organ systems, including the nervous system. To search for neurological biomarkers of LongC, we investigated the soluble proteins present in the plasma and the proteins associated with plasma neuronal-enriched extracellular vesicles (nEVs) in 33 LongC patients with neurological impairment (nLongC), 12 COVID-19 survivors without any LongC symptoms (Cov), and 28 pre-COVID-19 healthy controls (HC). COVID-19 positive participants were infected from 2020-2022, not hospitalized, and were vaccinated or unvaccinated before infection. IL-1b was significantly increased in both nLongC and Cov and IL-8 elevated in only nLongC. Both brain-derived neurotropic factor and cortisol were significantly elevated in nLongC and Cov compared to HC. nEVs from people with nLongC had significantly elevated protein markers of neuronal dysfunction, including amyloid beta 42, pTau181 and TDP-43. This study shows chronic peripheral inflammation with increased stress after COVID-19 infection. Additionally, differentially expressed nEV neurodegenerative proteins were identified in people recovering from COVID-19 regardless of persistent symptoms.

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.

Approximately 300 different types of blood groups are identified so far, the ABO and Rh antigens are still the clinically most significant and genetically most polymorphic of all human blood group systems to date. A total of 200 unrelated individuals from Uttar Pradesh were studied for the phenotype and allele frequency distribution of ABO and Rh (D) blood groups. In total 200 samples analyzed, phenotype B blood type has the highest frequency 36.5% (n=73), followed by O (34.5%; n=69), A (20.5%; n=41) and AB (8.5%; n=17). The O, A and B frequencies were 0.5849, 0.1571 and 0.2580 respectively. The overall phenotypic frequencies of ABO blood groups were B>O>A>AB. The variation in phenotypic frequencies between male and female might be due to small sample size of male sample. The allelic frequency of Rh-negative was 0.2.

Clinically, knowing the number of red blood cells (RBCs) and white blood cells (WBCs) helps doctors to make the better decision on accurate diagnosis of numerous diseases. The manual cell counting is a very time-consuming and expensive process, and it depends on the experience of specialists. Therefore, a completely automatic method supporting cell counting is a viable solution for clinical laboratories. This paper proposes a novel blood cell counting procedure to address this challenge. The proposed method adopts SegNet - a deep learning semantic segmentation to simultaneously segment RBCs and WBCs. The global accuracy of the segmentation of WBCs, RBCs, and the background of peripheral blood smear images obtains 89% when segment WBCs and RBCs from the background of blood smear images. Moreover, an effective solution to separate grouped or overlapping cells and cell count is presented using Euclidean distance transform, local maxima, and connected component labeling. The counting result of the proposed procedure achieves an accuracy of 93.3% for red blood cell count using dataset 1 and 97.38% for white blood cell count using dataset 2.

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.

Self-organized criticality (SOC) is a celebrated paradigm from the 90’s for understanding dynamical systems naturally driven to its critical point, where the power-law dynamics taking place make predictions practically impossible, such as in stock prices, earthquakes, pandemics and many other problems in science related to phase transitions. Shortly thereafter, it was realized that traffic flow might be in the SOC category, implying that conventional traffic management strategies seeking to maximize the local flows can become detrimental. This paper shows that the Kinematic Wave model with triangular fundamental diagram, and many other related traffic models, indeed exhibit SOC, thanks in part to the fractal nature of traffic exposed here on the one hand, and our need to get to our destinations as soon as possible, on the other hand. Important implications for congestion management of traffic near the critical region are discussed, such as: (i) Jam sizes obey a power-law distribution with exponent 1/2, implying that both its mean and variance become ill-defined and therefore impossible to estimate. (ii) Traffic in the critical region is chaotic in the sense that predictions becomes extremely sensitive to initial conditions. (iii) However, aggregate measures of performance such as delays and average speeds are not heavy tailed, and can be characterized exactly by different scalings of the Airy distribution, (iv) Traffic state time-space “heat maps” are self-affine fractals where the basic unit is a triangle, in the shape of the fundamental diagram, containing 3 traffic states: voids, capacity and jams. This fractal nature of traffic flow calls for analysis methods currently not used in our field.

Acquisition of real-time hydraulic data is an essential component for flood forecasting. However, we frequently face difficulties in obtaining discharge data using classical contact methods during high magnitude floods and for systems experiencing rapid hydro-geomorphological adjustment. Therefore, we developed low-cost, non-contact sensors and platforms that are designed to overcome these difficulties. These advances enable flood flow properties to be monitored at multiple locations across a river catchment, at low-cost, and communicated in near real-time by using an image velocimetry method. This is an optics-based approach for stream flow measurement using commercially available near-infrared digital cameras to acquire video footage in full HD (30fps). Video footage is then subjected to optical flow tracking techniques based on cross-correlation, and feature-based tracking, enabling the displacement rates of detected features (for example natural foam, seeds, woody debris, and turbulent structures) to be computed. This manual provides step by step guidance to install an image-based gauging station. It contains the list of necessary components, the calibration process of a new camera and the assembly procedure of the system.

While laminar flow heat transfer and mixing in microfluidic geometries has been investigated experimentally, as has the effect of geometry-induced turbulence in microfluidic flow (it is well documented that turbulence increases convective heat transfer in macrofluidic flow), little literature exists investigating the effect of electrokinetically-induced turbulence on heat transfer at the micro scale. Using recently observed experimental data, this work employed computational fluid dynamics coupled with electromagnetic simulations to determine if electrokinetically-forced, low-Reynolds number turbulence could be observed in a rectangular microchannel with using Newtonian fluids. Analysis of the results was done via comparison to the experimental criteria defined for turbulent flow. This work shows that, even with a simplified simulation setup, computational fluid dynamics (CFD) software can produce results comparable to experimental observations of low-Reynolds turbulence in microchannels using Newtonian fluids. In addition to comparing simulated velocities and turbulent energies to experimental data this work also presents initial data on the effects of electrokinetic forcing on microfluidic flow based on entropy generation rates.

Flow sensing in hostile environment is of increasing interest for applications in automotive, aerospace, and chemical and resource industries. Compared to their counterparts, thermal flow sensors are attractive candidates due to the ease of fabrication, lack of moving parts and higher sensitivity. Recently, a number of thermal flow sensor prototypes have been reported in the literature demonstrating the measurement of fluid flows under hostile conditions. This paper summarizes the concept of thermal flow sensing, operational modes and transduction mechanisms. Then, the choice of materials and their corresponding properties are presented in details. The paper also reports recent progress in the development of thermal flow sensors for harsh environment. In addition, the issues and considerations in packaging are reviewed. Finally, we conclude the review with the future prospects.

Coptisine (Cop) exerts a neuroprotective effect in central nervous system disease, particularly ischemic stroke. However, its protective mechanism is still unclear. This study aimed to investigate the protective effect of Cop on cerebral ischemia-reperfusion (IR) rats with a middle cerebral artery occlusion model by integrating a gas chromatography-mass spectrometry (GC-MS) based metabolomics approach with biochemical assessment. Our results showed that Cop could improve neurobehavioral function and decrease the ischemia size in IR rats. In addition, Cop was found to decrease inflammatory mediators (e.g., prostaglandin D2 (PGD2) and tumor necrosis factor-α (TNF-α) and attenuate oxidative stress response (e.g., increase the superoxide dismutase (SOD) expression and decrease 8-iso-PGF2α level). Furthermore, GC-MS based cerebrospinal fluid (CSF) metabolomics analysis indicated that Cop influenced the level of glycine, 2,3,4-trihydroxybutyric acid, oleic acid, glycerol, and ribose during IR injury. Cop exhibited a good neuroprotective effect against cerebral IR injury and metabolic alterations which might be mediated through its antioxidant and anti-inflammatory property.

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

Rapid isolation of white blood cells (WBCs) from whole blood is an essential part of any WBC examination platform. However, most conventional cell separation techniques are labor-intensive and low throughput, require large volumes of samples, need extensive cell manipulation, and have low purity. To address these challenges, we report the design and fabrication of a passive, label-free microfluidic device with a unique U-shaped cross-section to separate WBCs from whole blood using hydrodynamic forces that exist in a microchannel with curvilinear geometry. It is shown that the spiral microchannel with a U-shaped cross-section concentrates larger blood cells (e.g., WBCs) in the inner cross-section of the microchannel by moving smaller blood cells (e.g., red blood cells (RBCs) and platelets) to the outer microchannel section and preventing them from returning to the inner microchannel section. Therefore, it overcomes the major limitation of a rectangular cross-section where secondary Dean vortices constantly enforce particles throughout the entire cross-section and decrease its isolation efficiency. Under optimal settings, more than 95% of WBCs can be isolated from whole blood under high-throughput (6 ml/min), high-purity (88%), and high-capacity (180 ml of sample in 1 hour) conditions. High efficiency, fast processing time, and non-invasive WBC isolation from large blood samples without centrifugation, RBC lysis, cell biomarkers, and chemical pre-treatments make this method an ideal choice for downstream cell study platforms.

Cannabinoids are prescribed to children with cerebral palsy (CP) despite limited evidence. We aimed to assess the prescription practices of cannabinoids in children with CP with a particular focus on indications, what kind of preparations are used and how well cannabinoids are tolerated. Furthermore, we investigated how physicians acquire knowledge on cannabinoid medication. We asked physicians with expertise in the care of children with CP about their prescription prac-tices of cannabinoids. Data was collected through an online survey, which was distributed by email. In addition to the demographic information of participants, we also inquired about the indications for the prescription of cannabinoids, about experiences regarding efficacy, and ob-served side effects of the therapy. Seventy physicians from Europe, North America and Australia completed the survey. Forty-seven participants were experienced in the treatment of children with CP by cannabinoids. The most common indication was epilepsy (69%), followed by spasticity (64%) and pain (63%). The pre-scribed preparations and doses varied considerably. Half of the participants evaluated the effect of the cannabinoids as moderate. Twenty-nine physicians reported side effects, most frequently drowsiness (26%), somnolence (19%), fatigue (13%), and diarrhea (13%). Despite the lack of evidence to date, cannabinoids are used to treat children with CP in a wide variety of indications. Randomized controlled trials in this vulnerable patient group are therefore of utmost importance.

This study explored the effects of a comprehensive health care program (CHCP) on blood pressure, blood glucose, body composition, and depression in older adults living alone. We used a quasi-experimental, two-group, pre-posttest design. The CHCP consisted of open lectures, health counseling, exercise classes, nutrition counseling, and self-help group meetings at a local senior welfare center. Fifty-eight subjects participated in this study, with thirty subjects in the experimental group and twenty-eight subjects in the control group. Data were analyzed using the descriptive statistics, χ²-test, and t-test. Comparisons of the pretest and posttest systolic blood pressure (t = - 2.530, p < .016) and blood glucose (t = 3.089, p < .004) between the experimental and control groups showed significant differences. In both the experimental (t = 3.949, p < .001) and control groups (t = 3.816, p < .002), depression symptoms showed a significant decrease post-test, compared with pre-test. Our findings infer that older adults require physical and psychosocial healthcare and that more efforts must be made to improve the general health and wellbeing of this population group.

(1) Background: The Gárdos channel (KCNN4) and Piezo1 are the best-known ion channels in the red blood cell (RBC) membrane. Nevertheless, the quantitative electrophysiological behavior of RBCs and its heterogeneity are still not completely understood.; (2) Methods: Here we use state-of-the-art biochemical methods to probe for the abundance of the channels in RBCs. Furthermore, we utilize automated patch-clamp, based on planar chips, to compare the activity of the two channels in reticulocytes and mature RBCs. Besides this characterization, we performed membrane potential measurements to demonstrate the effect of channel activity and interplay on the RBC properties.; (3) Results: Both, Gárdos channel and Piezo1, albeit their average copy number of activatable channels per cell is in the single digit range, can be detected by transcriptome analysis of reticulocytes. Proteomics analysis of RBCs could only detect Piezo1 but not the Gárdos channel. Furthermore, they can be reliably measured in the whole-cell configuration of the patch-clamp method. While for the Gárdos channel the activity is higher in reticulocytes compared to mature RBCs, for Piezo1 the tendency is the opposite. While the interplay between Piezo1 and Gárdos channel cannot be followed using the patch-clamp measurements, it could be proved based on membrane potential measurements in populations of intact RBCs.; (4) Conclusions: We discuss the Gárdos channel and Piezo1 abundance, interdependencies and interactions in the context of their proposed physiological and pathophysiological functions, which are the passing of small constrictions, e.g., in the spleen, and their active participation in blood clot formation and thrombosis.

Background: Glioblastoma is the deadliest, yet most common, brain tumor in adults, with poor survival and response to aggressive therapy. Therapeutic failure results from a number of causes inherent to these tumors. Imaging, computational, and drug delivery approaches can aid in the quest to access and kill each tumor cell in patients. One factor, interstitial fluid flow, is a driving force therapeutic delivery. However, convective and diffusive transport mechanisms are un-der-studied. In this study, we examine the application of a novel image analysis method to meas-ure fluid flow and diffusion in glioblastoma patients with MRI and compare to patient outcomes. Methods: Building on a prior imaging methodology tested and validated in vitro, in silico and in preclinical models of disease, here we apply our analysis method to archival patient data from the Ivy GAP dataset. Results: We characterize interstitial fluid flow and diffusion patterns in patients. We find strong correlations between flow rates measured within tumors and in the surrounding parenchymal space, where we hypothesized that velocities would be higher. Looking at overall magnitudes, there is significant correlation with both age and survival in this patient cohort. Additionally, we find that tumor size nor resection significantly alter the velocity magnitude. Last, we map the flow pathways in patient tumors and find variability in degree of directionality that we hypothesize in future studies may lead to information concerning treatment, invasive spread, and progression. Conclusions: Analysis of standard DCE-MRI in patients with glioblastoma offers more infor-mation regarding transport within and around tumor, can be measured post-resection and mag-nitudes correlate with patient prognosis.

Metal foams are widely studied as possible tools for the enhancement of heat transfer from hot bodies. The basic idea is that a metal foam tends to increase significantly the heat exchange area between the hot solid body and the external cooling fluid. For this reason, this class of porous materials are considered as good candidates for an alternative to finned surfaces, with different pros and cons. Among the pros, we mention the generally wider area of contact between solid and fluid. Among the cons is the difficulty of producing different specimens with the same inner structure, with the consequence that their performance may be significantly variable. This paper will offer a survey of the literature with a focus on the main heat transfer characteristics of the metal foams. Then, a numerical simulation of the heat transfer at the pore scale level for an artificial foam with a spatially periodic structure will be discussed. Finally, these numerical results will be employed to assess the macroscopic modelling of the flow and heat transfer in a metal foam.

Pollution of sub-surface water reservoirs mainly rivers and streams through contaminated water point sources (CWPS) was studied. The objective was to formulate a discrete time delay mathematical model which describes the dynamics of reservoir pollution using mixing-problem processes that involve single species contaminants such as nitrates, phosphorous and detergents. The concentration of pollutants was expressed as a function of the inflow and outflow rates using the principle for the conservation of mass. Systems of ODEs generated from principles of mixing problems were refined into a system of DDEs so that the concentration of pollutant leaving the reservoir at time would be determined at some earlier instant, for the delay. The formulated model is a mathematical discrete time delay model which would be used to describe the dynamics of sub-surface water reservoir pollution. The results from the validation of the model were analyzed to determine how time delays in the mixing processes affect the rate of particle movement in water reservoirs.

Ischemia stroke is one of a clinically common cerebrovascular disease. And Inhibition of brain tissue ischemia and reperfusion-induced damage, especially apoptosis, has an irreplaceable protective effect on ischemic nerves, and has special significance for the treatment of patients after treatment. However, the development of neuroprotective drugs still has certain challenges. Radix scrophulariae as a valuable medicine, has been discovered to has neuroprotective effects. Our researches initially proved that Radix scrophulariae aqueous extract (RSAE) exerting a neuroprotective effects on cerebral ischemia and reperfusion (I/R) injury in oxygen glucose deprivation and reperfusion (OGD/R)-induced PC12 cells and middle cerebral artery occlusion/reperfusion (MCAO/R) model mice, were associated with attenuation of infarct volume, brain water content, nitric oxide (NO) and malondialdehyde (MDA), inhibiting I/R-induced damage by reducing the levels of LDH release, improving anti-oxidant capacity by upregulating the SOD, GSH-Px and CAT activity, stabilizing mitochondrial membrane potential, reducing neuronal apoptosis, necrosis and neuronal loss by regulating the expression of anti-apoptotic BCL-2and pro-apoptotic protein Bax, and elucidating downregulate the phosphorylation levels of MAPK pathways. Our findings may elaborate the neuroprotective effects and potential mechanisms of RSAE on focal cerebral I/R injury in mice. Since, Radix scrophulariae, as a potential neuroprotective natural plant, has originally been identified to, our results may offer directions and clues for discovering new active compounds or drugs for treatment of ischemic stroke, which allows us to discover many new natural active chemicals by chemical separation and identification, and provide new insights into therapeutic targets in stroke patients.

Horse riding therapy, also known as hippotherapy, is a popular treatment for children with cerebral palsy (CP). However, the need for trained therapists, massive land use, and expensive maintenance of the horse ranch makes hippotherapy not affordable or even available for most patients in Indonesia. This problem motivates us to consider mechanical horse riding simulator machines to replace actual horse hippotherapy. However, most patients are children and are easily bored when asked to do monotonous activities for an extended period. The room setting also does not give the patient visual inputs that usually help motivates the children in real-horse hippotherapy activities. To solve this problem, we designed an exercise game (exergaming) software which we named \textit{Sirkus Apel}, providing the patients with fun activities while doing the therapy. We also design an inertial sensor-based controller that lets the patients control the in-game horse by their back movements, which also benefits CP patients. To make the visual input enjoyable to the user while also considering the user's safety, we built a convex mirror-based dome virtual reality to provide an immersive 3-D experience. We then project the game content to the dome to provide an immersive experience to the patients making it as if they are riding a real horse inside the game.

We present our experience with the implantation of flow diverter stents (FDSs) for the management of intern carotid artery (ICA) dissections in tortuous tonsillar loop segments. 16 patients (10 women, 62.5%; mean age 39±8 years; median baseline NIHSS 13; median ASPECTS 8.5) with acute ischemic stroke due to ICA dissection in a tortuous tonsillar loop segment, with/without large intracranial vessel thrombotic occlusion, from 6/2015−2/2022 were included in this retrospective study under a waiver of informed consent. An FDS device was deployed from the petrous ICA toward the upper cervical ICA, completely covering the tonsillar loop. Stentriever-assisted thrombectomy was performed when indicated. A dual antiplatelet regimen was used during and after the procedure. Thrombocyte inhibition levels were evaluated before, during, and after the intervention. The ICA occlusion/near occlusion was successfully recanalized in all 16 patients with postangioplasty residual stenosis of 34±14% (range 0−50%). Stent-assisted embolectomy was performed in 15/16 patients (93.7%), achieving revascularization (TICI 2b−3) in all. There were no procedural complications and no intraprocedural embolic events; one asymptomatic petechial hemorrhage was detected. At 3-month follow-up, mRS 0−2 was seen in all patients. This report provides pilot data for a subsequent study on the use of flow diverter stents for ischemic cerebrovascular conditions. Our encouraging preliminary results await confirmation from further experience and prospective randomized studies.

Parkinson’s disease (PD) is the second most common degenerative disease which may cause blood pressure abnormalities due to autonomic dysfunction. Early morning rise of blood pressure which is called morning surge is found to be related with some cardiovascular diseases when it is exaggerated. We wanted to search the relation of Morning blood pressure surge (MBPS) and inflammation in PD. Method: Ambulatory blood pressure monitoring for 24 hours, fibrinogen to albumin ratio, hs-CRP are used in this retrospective study. Fifty idiopathic PD patients and 50 age and sex matched control cases were included. MBPS, it has been defined as the difference between morning BP (measured 2 hours after awakening) and the lowest night-time BP. Body mass index (BMI) is used as an independent variable. Results: Median value of MBPS for PD group (21,63) was significantly different from the control group values (18,63) (p

Background: Although the link between environmental lead exposure and several patterns of cardiovascular disease (CVD) has been reported, its association with silent myocardial infarc-tion (SMI) has not been explored. We aimed to assess the association between blood lead levels (BLL) and risk of SMI. Methods: This analysis included 7283 (mean age 56.1±2.52 years, 52.5% women) participants from the Third National Health and Nutrition Examination Survey who were free of clinical CVD. Ascertainment of BLL done using graphite furnace atomic absorption spectrophotometry. SMI defined as ECG evidence of MI without history of MI. Multivariable lo-gistic regression analysis was used to examine the association between SMI and BLL. Results: SMI was detected in 120 participants corresponding to an unweighted prevalence of 1.65%. Par-ticipants with higher levels of BLL had higher prevalence of SMI (0.4%, 0.9%, and 2.4% across BLL tertiles; p-value

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

The gut-liver axis plays a pivotal role in the development of liver diseases, necessitating exploration into substances capable of modulating the microbiota to prevent dysbiosis. Over the past decade, diverse therapeutic approaches have emerged to target pathogenic factors involved in the hepatic gut microbiota axis. This study investigated the impact of a supplement with hepatoprotective activity, containing extracts of Silybum marianum, prebiotics, probiotics, n-3 polyunsaturated fatty acids, minerals, and vitamins on hematological markers of liver functions and on the intestinal microbiota of 10 adult dogs with metabolic liver disease over a 35-day time span. Animals underwent clinical and laboratory evaluations every 7 days, before administration of the supplement (T0) and after 7, 14, 21, 28 and 35 days (T1, T2, T3, T4 and T5). In comparison to T0, a significant (P&lt;0.05) decrease of AST activity was measured at T2, T3, T4 and T5. The activity of ALP, glucose and CRP significantly decreased (P&lt;0.05) at T3, T4, and T5. The alpha diversity of the fecal microbiota significantly decreased (P&lt;0.05) only at T1, a high variability was observed between dogs. The total short-chain fatty acid and lactic acid were also lower at T1 (P&lt;0.05) in comparison to the other times of sampling. The beta diversity of fecal microbiota failed to find a clear pattern in relation to the sampling times. These results underscore the usefulness of the supplement on liver function and highlight high individual variability in its interaction with the fecal microbiome.

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 study aimed to assess the prognostic significance of total leukocyte count (TLC) and hemoglobin (Hb) levels upon admission for patients with acute pulmonary embolism (PE), considering the European Society of Cardiology (ESC) model for mortality risk. 1622 patients from a regional PE registry were included. Decision tree statistics were employed to evaluate TLC and Hb's prognostic value, both independently and in conjunction with the ESC model. Results indicated all-cause and PE-related in-hospital mortality rates of 10.7% and 6.5% respectively. Subgrouping patients based on TLC cutoff values (≤11.2, 11.2-16.84, &gt;16.84 x10^9/L) revealed increasing all-cause mortality risks (7.0%, 11.8%, 30.2%). Incorporating Hb levels (≤126 g/L or above) further stratified the lowest risk group into two strata with all-cause mortality rates of 10.1% and 4.7%. Similar trends were observed for PE-related mortality. Notably, TLC improved risk assessment for intermediate-high risk patients within the ESC model, while Hb levels enhanced mortality risk stratification for lower risk PE patients in the ESC model for all-cause mortality. In conclusion, TLC and Hb levels upon admission can refine the ESC model's mortality risk classification for patients with acute PE, providing valuable insights for improved patient management.

An aneurysm is a vascular malformation, it can be classified according to its location (cerebral, aortic); and according its shape (saccular, fusiform, and mycotic). The study of blood flow interaction with the aneurysms has gained attention from physicists an engineers in recent years. Shear stresses, oscillatory shear index (OSI), gradient oscillatory number (GON), and residence time had been used as potential variables to describe the hemodynamics as well as the origin and evolution of aneurysm. However, the causes of aneurysms and the hemodynamics conditions that promote the growth of these structures are still under debate. The present work presents numerical simulation on three aneurysms: 2 aortic and 1 cerebral. The results shows that the blood rheology is not relevant for aortic aneurysms, however, for cerebral aneurysm could play a relevant role in the hemodynamics. The turbulence models evaluated show equivalent results in both cases. Lastly, a simulation considering the fluid-structure interaction (FSI) shows that this phenomenon is the dominant factor for aneurysms simulation.

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.

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.

P-glycoprotein (Pgp) determines resistance to a broad spectrum of drugs in glioblastoma multiforme (GB) because it is highly expressed in GB stem cells and in brain-blood barrier (BBB), the peculiar endothelium surrounding brain. Inhibiting Pgp activity in BBB and GB is still an open challenge. Here, we tested the efficacy of a small library of tetrahydroisoquinoline derivatives with an EC₅₀ for Pgp < 50 nM, in primary human BBB cells and in patients-derived GB, from which we isolated differentiated/adherent cells (AC, i.e. Pgp-negative/doxorubicin-sensitive cells) and stem cells (neurospheres, NS, i.e. Pgp-positive/doxorubicin-resistant cells). At 1 nM, 3 compounds increased the delivery of doxorubicin, a typical substrate of Pgp, across BBB monolayer, without altering expression and activity of other transporters. The compounds increased the drug accumulation within NS, restoring necrosis, apoptosis and reduction in cell viability induced by doxorubicin. In co-culture systems, the compounds added to the luminal face of BBB increased the delivery of doxorubicin to NS growing under BBB and rescued the drug’s cytotoxicity. Our work identified new ligands of Pgp active at low nanomolar concentrations, that effectively reduce Pgp activity in BBB and GB, and can improve chemotherapy efficacy in this tumor.

Astringency is an important sensory characteristic of food and beverages containing polyphenols. However, astringency perception in elderly people has not been documented. The aim of the present work was to evaluate sensitivity to astringency as a function of age and salivary flow. Fifty-four panellists, including 30 elderly people (age=75±4.2 years) and 24 young people (age=29.4±3.8 years), participated in this study. Astringency sensitivity was evaluated by the 2-alternative forced choice (2-AFC) procedure using tannic acid solutions. Whole saliva was collected for 5 min before and after sensory tests. The results showed that the astringency threshold was significantly higher in the elderly group than in the young group. Moreover, a negative correlation between salivary flow and threshold was observed in the young group only. These results showed a difference in oral astringency perception as a function of age for the first time. This difference can be linked to salivary properties that differ as a function of age.

The paper argues that universal approaches to infiltration and drainage in permeable media that pivot around capillarity and that led to dual porosity, non-equilibrium, or preferential flow need to be replaced by a dual process approach. One process has to account for relatively fast infiltration and drainage based on Newton's shear flow, while the other one is responsible for storage and relatively slow redistribution of soil water by focusing on capillarity. Already Schumacher (1864) postulated two separate processes. However, Buckingham's (1907) and Richards' (1931) apparent universal capillary-based approach to flow and storage of water in soils dominated. The paper introduces the basics of Newton's shear flow in permeable media. It presents experimental support for the four presumptions of (i) sharp wetting shock fronts; (ii) that move with constant velocities; (iii) atmospheric pressure prevails behind the wetting shock front; (iv) laminar flow. It further discusses the scale tolerance of the approach, its relationship to Darcy's (1856) law, and its extension to solute transport.

Comparison between hydraulic and hydrologic computational methods is conducted in this study, regarding prismatic open channels under unsteady subcritical flow conditions. One-dimensional unsteady flow continuity and momentum equations are solved using explicit and implicit finite difference schemes for a symmetrical trapezoidal cross section, where the flow discharge and depth are the dependent variables. The results have been compared to those derived from Muskingum-Cunge hydraulic/hydrologic method as well as the commercial software HEC-RAS. The results from explicit and implicit code compare well to those from commercial software and hydraulic/hydrologic methods for long prismatic channels, thus directing the hydraulic engineer to quick preliminary design of prismatic open channels for unsteady flow with satisfactory accuracy.

The present study provides molecular insight into the mechanisms underlying energy dissipation and lubrication of a smooth contact lubricated by an ionic liquid. We have performed normal and lateral force measurements with a surface forces apparatus and by colloidal probe atomic force microscopy on following model systems: 1-ethyl-3-methyl imidazolium bis-(trifluoro-methylsulfonyl)imide, in dry state and in equilibrium with ambient (humid) air; the surface was either bare mica or functionalized with a polymer brush. The velocity-dependence of the friction force reveals two different regimes of lubrication, boundary-film lubrication, with distinct characteristics for each model system, and fluid-film lubrication above a transition velocity V*. The underlying mechanisms of energy dissipation are evaluated with molecular models for stress-activated slip and flow, respectively. The stress-activated slip assumes that two boundary layers (composed of ions/water strongly adsorbed to the surface) slide pass each; the bond dynamics and the strength of the interaction at the slip plane dictate the change in friction -decreasing, increasing or remaining constant- with velocity in the boundary-film lubrication regime. Above a transition velocity V*, friction monotonically increases with velocity in the three model systems. Here, layers of ions slide past each (“flow”) under a shear stress and friction depends on a shear-activation volume that is significantly affected by confinement. The proposed friction model provides a molecular perspective of the lubrication of smooth contacts by ionic liquids and allows identifying the physical parameters that control friction.

According to the World Health Organisation ischemic stroke is the second leading cause of death in the world. More frequent it is caused by brachiocephalic arteries (BCA) atherosclerosis. Timely detection of the atherosclerosis and it`s unstable course can allow a timely response to potentially dangerous changes and reduce the risk of vascular complications. Omics technologies allow us to identify new biomarkers that we can use in diagnosing diseases. The research included 90 blood plasma samples. The first group - 52 patients with severe atherosclerotic lesions, second group - 38 patients with no BCA atherosclerosis. Targeted and panoramic lipidomic profiling of blood plasma was carried out. There is a statistically significant difference (р

Blood-based biomarkers for early detection of recurrence have a significant clinical impact on the improved management of breast cancer patients, as cancer recurrence results in poor prognosis. This study aimed to investigate if the measurement of blood endocan in breast cancer patients with high ESM1 expression could be an effective tool to detect postoperative recurrence compared with existing tumor markers. Blood was collected before and after the tumor resection from the mouse models of breast cancer, and endocan levels were measured while visualizing metastatic recurrence with noninvasive luminescence imaging. In clinical settings, blood was withdrawn from 16 breast cancer patients before and after the tumor resection, and the effect of lumpectomy on blood endocan level was evaluated. Additionally, the blood endocan from 20 patients diagnosed with postoperative recurrence was measured, and their positivity rate for endocan was compared with that for serum carcinoembryonic antigen (CEA) or cancer antigen 15-3 (CA15-3). Our preclinical and clinical experiments revealed that blood endocan levels reflected tumor burden. Furthermore, over 60% of patients suffering from postoperative recurrence who tested negative for CEA or CA15-3 were positive for endocan. Our results support the clinical significance of endocan in breast cancer patients for detecting breast cancer recurrence.

Severe COVID-19 alters the biochemical and morphological characteristics of blood cells in a wide variety of ways. To date, however, the vast majority of research has been devoted to the study of leukocytes, while erythrocyte morphological changes have received significantly less attention. The purpose of this research was to identify erythrocyte types that were unique to COVID-19, compare the number of different poikilocyte types, and measure erythrocyte sizes to provide data on size dispersion. Red blood cells obtained from 6 control donors (800-2200 cells for each donor) and 5 COVID-19 patients (800-1900 cells for each patient) were examined using low voltage scanning electron microscopy. We did not discover any forms of poikilocytes that would be unique to COVID-19. Among COVID-19 patients, we observed an increase in the number of acanthocytes (p=0.01) and a decrease in the number of spherocytes (p=0.03). In addition, our research demonstrates that COVID-19 causes an increase in the median (p=0.004) and interquartile range (p=0.009) when assessing erythrocyte size.

Abstract: The ability to detect several types of cancer using a non-invasive, blood-based test holds the potential to revolutionize oncology screening. We mined tumor methylation array data from the Cancer Genome Atlas (TCGA) covering 14 cancer types and identified two novel, broadly oc-curring methylation markers at TLX1 and GALR1. To evaluate their performance as a general-ized blood-based screening approach, along with our previously reported methylation bi-omarker, ZNF154, we rigorously assessed each marker individually or combined. Utilizing the TCGA methylation data and applying logistic regression models within each individual cancer type, we found that the three-marker combination significantly increased the average area under the ROC curve (AUC) across the 14 tumor types compared to single markers (p= 1.158e-10; Friedman test). Furthermore, we simulated dilutions of tumor DNA into healthy blood cell DNA and demonstrated increased AUC of combined markers across all dilution levels. Finally, we evaluated assay performance in bisulfite sequenced DNA from patient tumors and plasma, in-cluding early-stage samples. When combining all three markers the assay achieved 100% sensi-tivity and specificity, as demonstrated in lung cancer plasma samples. In patient plasma from hepatocellular carcinoma, ZNF154 alone yielded the highest combined sensitivity and specificity values averaging 68% and 72%, whereas multiple markers could achieve higher sensitivity or specificity, but not both. Altogether this study presents a comprehensive pipeline for the identifi-cation, testing and validation of multi-cancer methylation biomarkers with a considerable poten-tial for detecting a broad range of cancer types in patient blood samples.

Fourier Transform Infrared Spectroscopy (FTIR), provides valuable biochemical information for biomedical analysis. It aids in identifying cancerous tissues, diagnosing diseases like acute pancreatitis or Alzheimer's, and has applications in genomics, proteomics, and metabolomics. A combination of FTIR and chemometrics constitute an approach that shows promise in fields like biology, forensics, food quality control, and plant variety identification. The study aims to explore the feasibility of ATR-FTIR spectroscopy for identifying ABO-blood types using spectroscopic tools. We employ various classifying algorithms, including Linear Discriminant Analysis (LDA), Naïve Bayes Classifier (NBC), Principal Component Analysis (PCA), and combinations of these methods, to detect A and B antigens and determine the ABO blood type. The results show that these algorithms predict the blood type to a greater extent than random selection, although they do not match the precision of biochemical blood typing tools. Additionally, our findings suggest a higher sensitivity of the methodology in identifying B antigens compared to A antigens.

Background The main aim of reconstructive surgery (RS) is to restore the integrity of soft tissues damaged by trauma, surgery, congenital deformity, burns or infection. Microsurgical techniques consist of harvesting tissues that are separated from the vascular sources of the donor site and anastomosed to the vessels of the recipient site. In these procedures, there are some preoperative modifiable factors that have the potential to influence the outcome of the flap transfer and its anastomosis. Methods Chronic inflammatory anaemia (ACD) is a constant condition in patients who have undergone RS and correlates with the perfusion of the free flap. In RS, it is important to maintain good tissue oxyporesis, avoiding blood hyperviscosity. From January 2017 to September 2019, we studied 16 patients (16 males, mean age 38 years) who underwent microsurgical procedures for RS. Haemoglobin (Hb) levels, Corpuscular Indexes, Transferring saturation (TSAT) ferritin concentrations and creatinine clearance have been measured the first day after surgery (T0), after the first week (T1) and after five weeks (T2). At T0 all patients showed low hemoglobin levels (average 7.4 g/dl, STD 0,71range 6,2-7,4 g dL-1), with an MCV of 72, MCH 28, MCHC 33, RDW 16, Sideremy 35, Ferritin 28, Ret% 1,36, TRF 277 and Creatinine Clearance 119. . We assessed all patients for clinical status, medical history and comorbidities before starting therapy. Results. In collaboration between the two departments, we started a therapeutic protocol with erythropoietic stimulating agents (ESAs) (Binocrit 6000 UI/week) and intravenous iron every other day, on the second day after surgery. Thirteen patients received ESAs and FCM (500-1000 mg per session), three patients received ESAs and iron gluconate (1 vial every other day). No patients received blood transfusions. No side effects were observed and, most importantly, no limb or flap rejection. Conclusions Preliminary data from our protocol show an optimal therapeutic response in a surgical setting with limited data in the scientific literature. The enrolment of further patients will allow us to validate this therapeutic protocol with statistically significant data.

ACE2 impact on the severity of COVID-19 is widely discussed but still controversial. To estimate its role in aspects of the main risk factors and comorbidities, we involved post-COVID-19 patients in Ternopil region (Ukraine). Recruitment period was July 2020 to December 2021. Medical records, treatment modalities and outcomes were recorded and analyzed. Serum human ACE2 protein was measured with Cusabio ELISA kits (Houston, TX, USA). Statistical analysis was performed with SPSS21.0 software (SPSS Inc., Chicago, IL, USA). The level of ACE2 serum protein was significantly higher (p < 0.001) in patients with mild symptoms compared to more severe course of disease, and inversely had changed from 1 to 90 days after recovery. In patients with mild COVID-19, ACE2 level significantly decreased over time, while among critical patients, it increased by 34.1percent. Such results could be explained by ACE2 shedding from tissues into circulation. Loss of the membrane-bound form of the enzyme decreases the virus entry into cells. Our studies did not identify any sex-related ACE2 serum levels correlation. The most common comorbidities were hypertension, cardiovascular diseases, respiratory diseases and diabetes mellitus. All comorbidities except respiratory diseases contribute to the severity of disease and correlate with ACE2 blood serum level.

Background: a 17 years-old girl with a Mitrofanoff appendicovesicostomy developed a large bladder clot due to hematuria after a surgical cystolithotomy in an augmented bladder. Trans-urethral approaches were not feasible due to a previous surgical closure of the bladder neck. Methods: after an unsuccessful trans-appendicovesicostomy bladder washing, the endoscopic evaluation was performed using a 14 Ch rigid cystoscope, surrounded by its own urethral sheath. The clot was progressively fragmented through the cystoscope and a urethral catheter under direct vision. Clot fragments were aspirated obtaining a complete evacuation; Results: the urethral sheath prevented damages to the appendicovesicostomy, allowing at the same time repeated accesses of the cystoscope into the neobladder and ensuring the success of the procedure; Conclusions: the use of urethral sheath 14 Ch though an appendicovesicostomy preserves both the stoma and the channel, making possible endoscopic procedures as blood clot evacuation into the neobladder.

The blood-brain barrier (BBB), built by brain endothelial cells (BECs), is impermeable to biologics. Liposomes and other nanoparticles are good candidates for delivery of biologics across the BECs, as they can encapsulate numerous molecules of interest in an omnipotent manner. The liposomes need attachment of a targeting molecule, as BECs unfortunately are virtually incapable of uptake of non-targeted liposomes from the circulation. Experiments of independent research groups have qualified antibodies targeting the transferrin receptor as superior for targeted delivery of nanoparticles to BECs. Functionalization of nanoparticles via conjugation with anti-transferrin receptor antibodies leads to nanoparticle uptake by endothelial cells of both brain capillaries and post-capillary venules. Reducing the density of transferrin receptor-targeted antibodies conjugated to liposomes limits uptake in BECs. Opposing the transport of nanoparticles conjugated to high-affine anti-transferrin receptor antibodies, lowering the affinity of the targeting antibodies or implementing monovalent antibodies increase uptake by BECs and allows for further transport across the BBB. The novel demonstration of transport of targeted liposomes in post-capillary venules from blood to the brain is interesting and clearly warrants further mechanistic pursuit. The recent evidence for passing targeted nanoparticles through the BBB shows great promise for future drug delivery of biologics to the brain.

Malaria comprises a spectrum of disease syndromes and the immune system is a major participant in malarial disease. This is particularly true in relation to the immune responses elicited against blood stages of Plasmodium-parasites that are responsible for the pathogenesis of infection. Mouse models of malaria are commonly used to dissect the immune mechanisms underlying disease. While no one mouse model of Plasmodium infection completely recapitulates all the features of malaria in humans, collectively the existing models are invaluable for defining the events that lead to the immunopathogenesis of malaria. Here we review the different mouse models of Plasmodium infection that are available, and highlight some of the main contributions these models have made with regards to identifying immune mechanisms of parasite control and the immunopathogenesis of malaria.

Surgeries that take place in medicine and dentistry or during any form of childbirth results in a significant amount of blood loss. The prevalent measurement methods that surgeons and anesthesiologists utilize as the “gold - standard” has several drawbacks. There are numerous other methods to measure blood loss, which, however, due to their impracticality and limitations, are not ideal either. This paper focuses on minimally invasive neurosurgery in particular, by taking into account a surgical technique known as Endoscopic Endonasal Transphenoidal surgery (EETS), which is used to treat pituitary tumors and adenomas. Along with the review of the existing literature pertaining to blood loss management, this paper proposes a modified electrode probe method along with the concept of usage, computer interface, and the system of integration. The probe is intended to measure the hematocrit count from the collected blood under all circumstances, such that the medical practitioner is assisted to improve the blood loss management technique for better patient recovery.

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.

Our understanding of how microbiome signatures are modulated in wild fish populations remains poorly known and has, until now, mostly been inferred from studies in commercial and farmed fish populations. Here, we have studied for the first time changes in the skin and blood microbiomes of the Salmo trutta population of the volcanic Kerguelen archipelago located at the northern limit of the Antarctic Ocean. Kerguelen is a natural framework of population expansion and a likely situation under further climate change in distribution areas. Our results showed that S. trutta of Kerguelen has a microbiome signature distinct from those of salmonids of the Northern Hemisphere. Our study also revealed that the skin and blood microbiomes differ between sedentary and migratory S. trutta. While 18 phyla were shared between both groups of trout, independent of the compartment, six phyla were unique to migratory trout. Further analyses showed that microbiome signatures undergo significant site-specific variations that correlate, in some cases, to the peculiarity of specific ecosystems. Our study also revealed the presence of potential pathogens at particular sites and the impact of abiotic factors on the microbiome, most notably due to the volcanic nature of the environment. This study contributes to a better understanding of the factors that modulate the microbiome signatures of migratory and sedentary fish populations. It will also help better monitor climate change's impacts on the colonization process in the sub-Antarctic region.

Introduction: Leprosy, caused by Mycobacterium leprae is one of the oldest infectious diseases in human history and its eradication is linked to poverty control, lack of basic sanitation, the fragility of health, and education services. Objective: To evaluate the frequency of blood groups (ABO/Rh) and the sociodemographic and clinical profile of Angolan patients with Leprosy treated at the Anti-Tuberculosis and Leprosy Dispensary in Luanda, the capital city of Angola. Methodology: A descriptive, introspective, cross-sectional study with a quantitative approach was carried out with 102 patients of Luanda, in the second half of 2021. Results: Of the 102 patients included in the study, the majority belonged to the ORh+ group (51.9%), followed by the BRh+ group (27.4%) and ARh+ (18.6%), most were under 51 years of age ( 87.3%), with low education (54.9%), coming from urban areas (44.1%). As for clinical conditions, most had a multibacillary infection (93.1%), diagnosed mainly by smear microscopy (75.5%) without other infection (79.4%), some of them with complications (28.4%) and individuals with non-O blood group showed changes in the blood count. Conclusion: Leprosy seems to be common in ORh+ individuals, it continues to affect especially those residing in areas of population agglomerations and with low education, presenting itself as a multibacillary infection, where changes in the blood count are greater in non-O individuals.