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.

In the last decade, the drone market has grown rapidly for both civil and military purposes. Due to their versatility, drones demand is constantly increasing, with several industrial players joining the venture to transfer urban mobility to the air. This has exacerbated the problem of noise pollution, mainly due to the relatively lower altitude of these vehicles and to the proximity of their routes to extremely densely populated areas. In particular, both the aerodynamic and aeroacoustic optimization of the propulsive system and of its interaction with the airframe are key aspects of the design of aerial vehicles for the success or the failure of their mission. The industrial challenge involves finding the best performance in terms of loading, efficiency and weight, and, at the same time, the most silent configuration. For this reason, research has focused on an initial localization of the noise sources and, on further analysis, of the noise generation mechanism, focusing particularly on directivity and scattering. The aim of the present study is to review the noise source mechanisms and the state-of-the-art technologies available in literature for its suppression, focusing especially on the fluid-dynamic aspects of low Reynolds numbers of the propulsive system and on the interaction of the propulsive-system flow with the airframe.

Circulating tumor DNA (ctDNA) in fluids has gained attention because ctDNA seems to identify tumor-specific abnormalities, which could be used for diagnosis, follow-up of treatment, and prognosis: the so-called liquid biopsy. Liquid biopsy is a minimally invasive approach and presents the sum of ctDNA from primary and secondary tumor sites. It has been possible not only to quantify the amount of ctDNA but also to identify (epi)genetic changes. Specific mutations in genes have been identified in the plasma of patients with several types of cancer, which highlights ctDNA as a possible cancer biomarker. However, achieving detectable concentrations of ctDNA in body fluids is not an easy task. ctDNA fragments present a short half-life, and there are no cut-off values to discriminate high and low ctDNA concentrations. Here, we discuss the use of ctDNA as a cancer biomarker, the main methodologies, the inherent difficulties, and the clinical predictive value of ctDNA.

When focusing on materials science in civil engineering, the current trend is to investigate the use of innovative solutions in order to enhance thermal and energy performances. This trend is amplified with the need for a sustainable development strategy for the construction sector. This paper assesses the integration of a Phase Change Material (PCM) in cement intended for building construction. The key characteristic of PCMs is their capacity to absorb energy and restore it. In building construction, this feature could be harnessed to save energy by incorporating PCMs in the materials used. In this study, passive integration of PCM in cement was tested and thermal properties of such an integration was assessed. The results provide insights into how PCMs affect cement as part of the concrete mixture, thus identifying the contribution of PCM-based cements in concrete mixtures.

Blood has certain significant physical properties, which the authors investigated. This paper provides values of surface tension and viscosity of blood at 37 °C, as well as relationship between them plotted on a cross-plot. By applying Hagen- Poiseuille equation and Jurin's law to the experimentally obtained data, the authors calculated with great accuracy viscosity and surface tension of blood. Evaluating both of the properties using described methods required from the authors to know the density of investigated liquid, which was found to be on average $\rho=1063,56 \frac{kg}{m^3}$. The authors took blood samples from 30 healthy subjects and determined aforementioned physical properties. There has been made a distinction in regard of a sex of the blood donor. Results indicate that both surface tension and viscosity are independent from sex of a subject, as well as indicate that there is no correlation between viscosity and surface tension of blood at 37\degree C. Average values of surface tension and viscosity were found to be $\sigma=5,241\pm 0,262 \cdot 10^{-2}\frac{J}{m^2}$ and $\eta=3,352\pm0,360 \cdot 10^{-3} Pa \cdot s$, respectively.

The one-dimensional MoS₂/carbon nanofibers (1D MoS₂/CNFs) are synthesized by electrospinning using exfoliated MoS₂ nanosheets and polyacrylonitrile as raw materials. The exfoliated MoS₂ nanosheets with size of about 150 nm are encapsulated in carbon nanofibers, and the free-standing MoS₂/CNFs can be easily cut into flexible tablet and directly used as binder-free anode for lithium storage. The resultant 1D MoS₂/CNFs exhibit a very high reversible capacity of 700 mAh g^-1 at 100 mA g^-1 after 50 cycles, high rate capacity (450 mAh g^-1 at 1000 mA g^-1 after 200 cycles) and good cycle stability.

A facilitative transport system exists on the blood brain barrier (BBB) that has been tacitly assumed to be a path for glutamate entry to brain. But glutamate is a non-essential amino acid whose brain content is much greater than plasma, and studies in vivo show that glutamate does not enter brain in material quantities except in those small regions with fenestrated capillaries (circumventricular organs). The situation became understandable when luminal (blood facing) and abluminal (brain facing) membranes were isolated and studied separately. Facilitative transport of glutamate and glutamine exist only on the luminal membranes whereas Na+-dependent transport systems for glutamate, glutamine and some other amino acids are present only on the abluminal membrane. The Na+-dependent cotransporters of the abluminal membrane are in a position to actively transport amino acids from the extracellular fluid (ECF) into the endothelial cells of the BBB. These powerful secondary active transporters couple the energy of the Na+-gradient to move glutamate and glutamine into the ECF whereupon glutamate can exit to blood on the luminal facilitative glutamate transporter. Glutamine may also exit brain on a separate facilitative transport system that exists on the luminal membranes or glutamine can be hydrolyzed to glutamate within the BBB thereby releasing ammonia that is freely diffusible. The γ-glutamyl participate cycle participates indirectly by producing oxoproline (pyroglutamate) that stimulates almost all secondary active transporters yet discovered in the abluminal membranes of the BBB.

Background: Globally, hot cooked refined rice is consumed in large quantities and is a major contributor to dietary glycaemic load. This study aimed to compare the glycaemic potency of hot and cold stored parboiled rice to widely available medium grain white rice. Method: Twenty-eight healthy volunteers participated in a three treatment experiment where postprandial blood glucose was measured over 120 minutes after consumption of 140g of rice. Three rice samples were freshly cooked medium-grain white rice, freshly cooked parboiled rice, and parboiled rice stored overnight at 4 ºC. All rice was served warm at 65 ºC. Chewing time was recorded. Results: The 24-hours cold-stored and reheated parboiled rice resulted in a 42% and 12% lower blood glucose concentration trajectory than freshly cooked medium-grain white rice and freshly cooked parboiled rice. Chewing time for 10g cold stored parboiled rice was 6 seconds (25%) longer and was considered more palatable, visually appealing and better tasting than freshly cooked medium grain (all P<0.05). Conclusions:. For regular consumers of rice reheating cooked rice after cold storage would lower the dietary glycaemic load and long term may reduce risk for type 2 and gestational diabetes. More trials are needed to identify the significance.

By using the particle swarm optimization algorithm for crystal structure prediction, we reveal a newly orthorhombic Cmcm structure of HfB4, which is more energetically superior to the previously proposed YB4-, ReP4-, FeB4-, CrB4-, and MnB4-type structures in the considered pressure range. The phonon dispersion and elastic constants calculations confirm that the new phase is dynamically and mechanically stable. The calculated large shear modulus (240 GPa) and high hardness (45.7 GPa) imply that the predicted Cmcm-HfB4 is a potential superhard material. Meanwhile, the directional dependences of the Young's modulus, bulk modulus, and shear modulus for HfB4 are systematically investigated. Further analyses of the density of states and electronic localization function indicate that the strong B-B and B-Hf covalent bonds greatly contribute to its high hardness and stability.

This paper reviews state of the art Additive Manufactured (AM) IN718 alloy intended for high temperature applications. AM processes have been around for decades and have gained traction in the past five years due to the huge economic benefit it brings to manufacturers. It is crucial for the scientific community to look into AM IN718 applicability in order to see a step-change in the production. Microstructural studies reveal that the grain structure plays a significant role in determining the fatigue lifespan of the material. Controlling IN718 respective phases such as the ϒ’', δ and Laves phase is seen to be crucial. Literature reviews have shown that the mechanical properties of AM IN718 were very close to its wrought counterpart when treated appropriately. Higher homogenization temperature and longer ageing were recommended to dissolve the damaging phases. Various surface enhancement techniques were examined to find out their compatibility to AM IN718 alloy that is intended for high temperature application. Laser shock peening (LSP) technology stands out due to the ability to impart low cold work which helps in containing the beneficial compressive residual stress it brings in high temperature fatigue environment.

Despite the development of technologies, modern methods of disposal of end-of-life tires most often represent either the incineration in cement kilns or the destruction of tires in special landfills, showing a lack of sustainable recycling of this valuable material. The fundamental role of recycling is evident, and the development of high-efficiency processes represents a priority for the European market. Therefore, investigation of end-of-life rubber processing methods is of high importance for manufacturers and recyclers of rubber materials. In this paper, methods of processing of end-of-life tires are reviewed in order to obtain rubber crumb, which can later be used in the production of new industrial rubber goods and composite The processes of separation end-of-life tire into fractions by type of materials using mechanical processing methods along with mechanochemical and mechanical processes of processing the materials of used tires in order to obtain crumb rubber of various fractions and chemical reactivity are considered.

The purpose of this work was to evaluate the suitability of recent US Food and Drug Administration (US-FDA) approved and marketed oral liquid, powder, or granule products for children in North America, to identify the next group of Active Pharmaceutical Ingredients (APIs) that have high potential for development as commercially available FDA-approved finished liquid dosage forms , and to propose lists of compounded nonsterile preparations (CNSPs) that should developed as commercially available FDA-approved finished liquid dosage forms as well as those that pharmacists should continue to compound extemporaneously. Through this identification and categorization process, the pharmaceutical industry, government, and the professions are encouraged to continue to work together to improve the likelihood that patients will receive high quality standardized extemporaneous CNSPs and US-FDA-approved products.

Background: Hypertension is a condition of a person's blood pressure being at a level above normal, hypertension treatment can be done herbally using avocado leaves. Avocado leaves can lower blood pressure because they contain active substances, namely flavonoids and quercetin. This research was conducted in the working area of the Tilango Health Center. Objective: This study aims to determine the effect of giving boiled water of avocado leaves on reducing blood pressure in the elderly with hypertension. Methods: Design This study used a two-group quasi-experimental pre-test - post-test design. The sample is the elderly who have hypertension, amounting to 125 people with purposive sampling technique. The research instrument used a questionnaire. Results: Statistical test using T-Test on blood pressure before and after the intervention was given a significance value of 0.000 (p-value < 0.05 ). Conclusion : This study concludes that there is a significant effect between giving avocado leaf boiled water on reducing blood pressure in the elderly with hypertension in the working area of the Tilango Health Center.

Thalassemia is genetic blood disease cause by absence or decrease of one or more of the globin chain synthesis. Beta thalassemia is characterized by one or more mutations in beta globin gene. Absence or reduced amount the of beta globin chains cause ineffective erythropoiesis which leads to anemia. Beta thalassemia has been further divided into three main forms: Thalassemia minor/silent carrier, major and intermedia. More severe form is thalassemia major in which patients depend upon blood transfusion for survival and high level of iron occur as a consequence of consistent blood transfusion. Over loaded iron invokes the synthesis of reactive oxygen species that are toxic in redundancy and triggering the impairment to vascular, endocrine and hepatic system. Thalassemia can be diagnosed and detected through various laboratory tests such as blood smear, prenatal testing (genetic testing of amniotic fluid), DNA analysis (genetic testing) and complete blood count. Treatment of thalassemia intermedia is symptomatic but it can also be managed by splenectomy and folic supplementation. While thalassemia major can be treated by transplantation of bone marrow, regular transfusion of blood and iron chelation treatment, stimulation of fetal hemoglobin production, hematopoietic stem cell transplantation and gene therapy.

Neuroscience has overwhelmingly and understandably focused on the synaptic modality of signal transmission. There is evidence, however, that from an evolutionary perspective, non-synaptic transmission (NST) preceded synaptic signaling. Moreover, in modern nervous systems, NST coexists and extensively interacts with synaptic transmission modifying neuronal dynamics. In fact, NST remains widespread in complex animals, especially within the interoceptive system where the dearth of insulating barriers such as myelin sheaths and the blood-brain barrier enhances the communication between neural and non-neural tissues mediated by NST. We suggest that this physiological arrangement makes a fundamental contribution to interoception¾the process of sensing visceral states¾which is an essential underpinning of the capacity to feel and the foundation of affective processing.

The recycling, incineration, and final disposal rate of municipal solid waste (MSW) are calculated based on the total amount of waste input to each facility in many countries. These statistic data have serious limitation in setting the national goal and policy for effective waste management because it is not considering the amount of foreign objectives in the process of each life-cycle stage. This case study is to estimate the actual rates of recycling, incineration, and final disposal by material flow analysis (MFA) after the collection of MSW in Korea. The actual rates of recycling, incineration and final disposal for MSW in 2016 were 49.9%, 32.9% and 23.1% respectively, indicating that the recycling rate was lower by 10.1%, while the incineration and final disposal rates were raised by 7.6% and 8.4% respectively, compared with the statistics for current MSW. In addition, the changed actual rates of recycling, incineration treatment, and final landfill, and variation of waste treatment charge according to treated amounts per treatment method was analyzed. This results of this study will contribute to establish national level of plan on effective waste management.

Flux-switching permanent magnet (FSPM) motors have gained increasing attention in the electric vehicles (EVs) applications due to the advantages of high power density, high efficiency. However, the heat sources of both permanent magnet (PM) and armature winding are located on the limited stator space in the FSPM motors, which may result in the PM overheated and irreversible demagnetization caused by temperature rise and it is often ignored in the conventional thermal analysis. In this paper, a new electrical-thermal two-way coupling design method is proposed to analyze the electromagnetic performances, where the change of PM material characteristics under different temperatures is taken into consideration. Firstly, the motor topology and design equations are introduced. Secondly, the demagnetization curves of PM materials under different temperatures are modeled due to PM materials are sensitive to the temperature. And based on the electrical-thermal two-way coupling method, the motor performances are evaluated in details, such as the load PM flux linkage and output torque. Then, the motor is optimized, and the electromagnetic performances between initial and improved motors are compared. Finally, a prototype motor is manufactured, and the results are validated by experimental measurements.

Blood perfusion quantification is important vital parameters in different diagnostic procedure, using infrared thermography imaging; it is reliable to use this technique as non-contact, non-invasive blood flow measurement method. Therefore, we developed a measurement protocol for blood flow over the arm's anterior surface. By using the superficial brachial and radial veins to be monitored under the impact of cold-excitation of (2 °C to 5 °C), the blood perfusion signal was detected using thermal imager of long-wave infrared spectral range (LWIR, 7μm - 14 μm). The simulation of Penne's bioheat transfer equation was performed to be compared with results obtained from the infrared thermography. Furthermore, the proposed blood flow monitoring using external adjusting of the excitation temperature, by using (cold-compress, or cold air-stream) applied to the region under testing. The signal detected resembles to the hemodynamic pulse of the superficial veins, in the definition of systolic and diastolic phases of the cardiac cycle. Moreover, statistical analysis applied to the BFIRT signals from 24 subjects to estimate the skin's mean temperature after recovery from the thermal excitation.

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

This paper presents a symmetrical topology for the design of solid-state transformer, made up of power switching converters, to replace conventional bulky transformers. The proposed circuitry not only reduces the overall size but also provides power flow control with the ability to be interfaced with renewable energy resources (RESs) to fulfill the future grid requirements at consumer end. Solid state transformer provides bidirectional power flow with variable voltage and frequency operation and has the ability to maintain unity power factor, and current total harmonic distortion (THD) for any type of load within defined limits of IEEE standard. Solid State Transformer offers much smaller size as compared to that of the conventional iron core transformer. MATLAB/Simulink platform is adopted to test the validity of the proposed circuit for different scenarios by providing the simulation results evaluated at 25 kHz switching frequency.

The cause-effect relationship between iron deficiency anemia (IDA) and osteoporosis has not been established in the general population. Thus, the current longitudinal study determined the role of IDA as a risk factor for osteoporosis by analyzing a large nationwide population-based sample. In a sample of 1,000,000 randomly sampled individuals from the 1998-2012 Taiwan National Health Insurance Research Database, patients with IDA (case group [n=35,751]) and individuals without IDA (control group [n=178,755]) were compared. Patients who were <20 years of age and who had pre-existing osteoporosis prior to the diagnosis of IDA were excluded. Each patient with IDA was age- and gender-matched to 5 individuals without IDA. The diagnoses of IDA and osteoporosis (coded using ICD-9CM) were further confirmed with blood test results and X-ray bone densitometry to ensure the accuracy of the diagnoses. Osteoporosis occurred more often among patients with IDA compared to individuals without IDA (2.27% vs. 1.32%, p<0.001). Cox proportional hazard analysis revealed that the risk for osteoporosis was significantly higher in the case than the control group (hazard ratio [HR]=1.74; 95% CI=1.61-1.88) and remained similar after adjustment for covariates (adjusted HR=1.81; 95% CI=1.67-1.97). Compared with individuals without IDA, the risk for osteoporosis was even higher for patients with IDA who received intravenous ferrum therapy (adjusted HR=2.21; 95% CI=1.85-2.63). In contrast, the risk for osteoporosis was reduced for patients with IDA who received a blood transfusion (adjusted HR=1.47; 95% CI=1.20-1.80). As a predictor, prior IDA is a significant and independent risk factor for development of osteoporosis. In contrast to blood transfusion treatment, the use of intravenous ferrum may further increase the risk for future osteoporosis.

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

Although most cases of COVID-19 are paucisymptomatic, severe disease is characterized by immune dysregulation, with a decreased type I interferon response, increased inflammatory indicators, surging IL-6, IL-10 and TNFα suggestive of cytokine storm, progressive lymphopenia, and abnormal blood clotting. Factors determining susceptibility to severe disease are poorly understood, although mortality correlates with increasing age and co-morbidities including diabetes and cardiovascular disease (CVD). Pyridoxal 5'-phosphate (PLP) tends to be insufficient in populations particularly vulnerable to COVID-19, including the elderly, the institutionalized, and people with diabetes and CVD, and PLP becomes further depleted during infection and inflammation. In turn, low PLP results in immune imbalance, as PLP is an essential cofactor in pathways regulating cytokine production, in particular type I interferons and IL-6, and in lymphocyte trafficking and endothelial integrity. Furthermore, normalizing PLP levels attenuates abnormalities in platelet aggregation and clot formation. Finally, PLP insufficiency induces excess secretion of renin and angiotensin, and hypertension. In inflammatory disease, pharmacological doses of PLP decrease circulating TNFα, IL-6 and D-dimer, and animal studies demonstrate that supplemental PLP shortens the duration and severity of viral pneumonia. Severe COVID-19 manifests as an imbalance in the immune response and the clotting system. Pharmacological PLP supplementation may therefore mitigate COVID-19 symptoms by alleviating both the immune suppression underlying viral spread and the pathological hypersecretion of inflammatory cytokines, as well as directly bolstering endothelial integrity and preventing hypercoagulability.

Mercury has a strong environmental impact since both its organic and inorganic forms are toxic and it represents a pollutant of global concern. Liquid Hg is highly volatile and it can be released during natural and anthropogenic processes in the hydrosphere, biosphere and atmosphere. In this study the distribution of Gaseous Elemental Mercury (GEM) and the total and leached mercury concentrations on paints, plasters, roof tiles, concretes, metals, dust and wood structures were determined in the main buildings and structures of the former Hg-mining area of Abbadia San Salvatore (Siena, Central Italy). The mining complex (divided into 7 units) covers a surface of about 65 ha and contains mining structures and managers and workers buildings. In this work, nine surveys of GEM measurements were carried out from July 2011 to August 2015 for the buildings and structures located in the units 2, 3 and 6. Moreover, detailed measurements were performed in February, April, July, September and December 2016 in the edifices and mining structures of Unit 6. GEM concentrations showed a strong variability in terms of space and time mostly depending on the distance from the building hosting driers, furnaces and condensers and ambient temperature, respectively. In the Unit 2 surveys carried out in the hotter period (from June to September) showed GEM concentrations up to 27,500 ng m⁻³, while in the Unit 6 they were on average much higher and occasionally they saturated the GEM measurement device (>50,000 ng m⁻³). Concentrations of total (in mg kg⁻¹) and leached (in μg L⁻¹) mercury measured in different building materials (up to 46,580 mg kg⁻¹ and 4,470 mg L⁻¹ for total and leached mercury, respectively) showed for the same type of material highly variable values in dependence on the edifice or mining structure from which they were collected. The results obtained in this study are of relevant interest for the operational cleanings to be carried out during the reclamation activities.

Increasing salt intake has substantial negative impacts on health and well-being. This review article focusses on the effect of salinity intrusion (SI) on the water quality and community health of coastal Bangladesh and to find out the effectiveness of interventions for reducing the negative effects of salinity. Saline water is a noteworthy reason for hypertension or high blood pressure in the coastal areas. Health status of women especially the pregnant women are vulnerable because of drinking water sodium (DWS) prompting to pre-eclampsia, high blood pressure and hypertension as well as infant mortality. Several interventions such as rainwater harvesting and Pond sand filter (PSF) system as well as managed aquifer recharge (MAR) usage and the integration of mixed sources were reviewed on the content of drinking water sodium (DWS). Although rainwater has the positive impact of low or no sodium intake on human health, it still possesses negative impacts from not having vital minerals. Despite what might be expected, in MAR a steady increment in sodium concentration through the span of the dry season was observed. It is, subsequently, important to increase awareness about drinking water sodium (DWS) intake by providing and adopting correct technological interventions.

The early embryonic heart is a multi-layered tube consisting of (1) an outer myocardial tube; (2) an inner endocardial tube; and (3) an extracellular matrix layer interposed between myocardium and endocardium, called “cardiac jelly” (CJ). During the past decades, research on CJ has mainly focused on its molecular and cell biological aspects. This review focuses on the morphological and biomechanical aspects of CJ. Special attention is given to (1) the spatial distribution and fiber architecture of CJ; (2) the morphological dynamics of CJ during the cardiac cycle; and (3) the removal/remodeling of CJ during advanced heart looping stages, which leads to the formation of ventricular trabeculations and endocardial cushions. CJ acts as a hydraulic skeleton displaying striking structural and functional similarities with the mesoglea of jellyfish. CJ not only represents a filler substance, facilitating end-systolic occlusion of the embryonic heart lumen. Its elastic components antagonize the systolic deformations of the heart wall and thereby power the refilling phase of the ventricular tube. Non-uniform spatial distribution of CJ generates non-circular cross sections of the opened endocardial tube (initially elliptic, later deltoid), which seem to be advantageous for valveless pumping. Endocardial cushions arise from non-removed remnants of the original CJ.

Additive manufacturing has already been established as a highly versatile manufacturing technique with demonstrated potential to completely transform conventional manufacturing in the future. The objective of this paper is to review the latest progress and challenges associated with the fabrication of multi-material parts using additive manufacturing technologies. Various manufacturing processes and materials used to produce functional components were investigated and summarized. The latest applications of multi-material additive manufacturing (MMAM) in automotive, aerospace, biomedical and dentistry field were demonstrated. Investigation on the current challenges were also carried out to predict the future direction of MMAM processes. It is concluded that the further research and development needed in the design of multi-material interfaces, manufacturing processes and material compatibility of MMAM parts are necessary.

The material derivative is important in continuum physics. This Letter shows that the expression $\frac{d }{dt}=\frac{\partial }{\partial t}+(\bm v\cdot \bm \nabla)$, used in most literature and textbooks, is incorrect. The correct expression $ \frac{d (:)}{dt}=\frac{\partial }{\partial t}(:)+\bm v\cdot [\bm \nabla (:)]$ is formulated. The solution existence condition of Navier-Stokes equation has been proposed from its form-solution, the conclusion is that "\emph{The Navier-Stokes equation has a solution if and only if the determinant of flow velocity gradient is not zero, namely $\det (\bm \nabla \bm v)\neq 0$.}"

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.

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

Preterm infants are at significant risk to develop reduced bone mineralization based on inadequate supply of calcium and phosphorus (Ca-P). Biochemical parameters can be used to evaluate the nutritional intake. The direct effect of nutritional intake on changes in biochemical parameters has not been studied. Our objective was to evaluate the effect of Ca-P supplementation on biochemical markers as serum (s)/urinary (u) Ca and P; alkaline phosphatase (ALP); tubular reabsorption of P (TrP) and urinary ratios for Ca/creatinin and P/creatinin in Very-Low-Birth-Weight infants on postnatal day 1, 3, 5, 7, 10, and 14. This observational study compared two groups with High (n = 30) and Low (n = 40) intake of Ca-P. Birth weight: median (IRQ) 948 (772-1225) vs. 939 (776-1163) grams; Gestational age: 28.2 (26.5-29.6) vs. 27.8 (26.1-29.4) weeks. Daily median concentrations of biochemical parameter were not different between the groups but linear regression mixed model analyses showed that Ca intake increased the uCa and TrP (p = 0.04) and decreased ALP (p = 0.00). Phosphorus intake increased sP, uP and uP/creat ratio and ALP (p ≤ 0.02) and caused decrease in TrP (p = 0.00). Protein intake decreased sP (p = 0.000), while low gestational age and male gender increased renal excretion of P (p < 0.03). Standardized repeated measurements showed that biochemical parameters were affected by nutritional intake, gestational age and gender.

Thermophysical characterization of three paraffin waxes (RT27, RT21 and RT35HC) is carried out in this study using DSC, TGA and transient plane source technics. Then, a numerical study of their melting in a rectangular enclosure is examined. The enthalpy-porosity approach is used to formulate this problem in order to understand the heat transfer mechanism during the melting process. The analysis of the solid-liquid interface shape, the temperature field shows that the conduction is the dominant heat transfer mode in the beginning of the melting process. It is followed by a transition regime and the natural convection becomes the dominant heat transfer mode. The effects of the Rayleigh number and the aspect ratio of the enclosure on the melting phenomenon are studied and it is found that the intensity of the natural convection increases as the Rayleigh number is higher and the aspect ratio is smaller. In the second part of the numerical study, a comparison of the performance of paraffins waxes during the melting process is conducted. Results reveals that from a kinetically RT21 is the most performant but in term of heat storage capacity, it was inferred that RT35HC is the most efficient PCM.

One of the most popular techniques for determining electrical properties of material is the free-space measurement technique. With the potential for new applications requiring efficient, accurate and broadband material measurement systems using higher millimeter-wave and terahertz frequencies, the free-space measurement method has received renewed interest. This is mainly due to its simplicity, favorable properties as a non-destructive method, and it allows transmission and reflection measurements without any physical contact with the sample. This paper reviews and discusses state- of-the-art free space material measurement systems, starting with the different measurement techniques available for material characterization, their important concepts, post-processing in determining their properties, and progress towards expanding their use at higher frequencies. Also, this paper reviews dielectric material characterization using the free space method focusing on their application extension towards the higher frequencies. Besides, the algorithms for conversion methods and usage of lens in free space material measurement system was discussed in this paper. Finally, a future perspective on the outlook of this free space method is presented prior to the conclusion.

Aiming at the damage detection and continuous monitoring of high efficiency composite structure, the method of carbon nano sensor embeded in the 3-D braided composite material specimen was put forward and the method of damage location for 3-D braided composite material was described. In this paper, the mechanical and electrical characteristics of carbon nano-fiber were analyzed. Considering the massive data of the health monitoring of composite processing, to ensure that the system has good real-time performance, quaternary matrix Singular Value Decomposition algorithm is proposed to simplify data and improve the efficiency of the algorithm. The existence of injury is determined and the damage location is calculated by comparing with key features of healthy specimen. Experimental results prove the method is feasible and effective.

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/.

Without protective and/or therapeutic agents the SARS-CoV-2 infection known as coronavirus disease 2019 (COVID-19) is quickly spreading worldwide. It has surprising transmissibility potential, since it could infect all ages, gender, and human sectors. It attacks respiratory, gastrointestinal, urinary, hepatic, and endovascular systems and can reach the peripheral nervous system (PNS) and central nervous system (CNS) through known and unknown mechanisms. The reports on the neurological manifestations and complications of the SARS-CoV-2 infection are increasing exponentially. Herein, we enumerate seven candidate routes, which the mature or immature SARS-CoV-2 components could use to reach the CNS and PNS, utilizing the within-body crosstalk between organs. The majority of SARS-CoV-2 infected patients suffer from some neurological manifestations (e.g., confusion, anosmia, and ageusia). It seems that although the mature virus did not reach the CNS or PNS of the majority of patients, its unassembled components and/or the accompanying immune-mediated responses may be responsible for the observed neurological symptoms. The viral particles and/or its components have been specifically documented in endothelial cells of lung, kidney, skin, and CNS. This means that the blood-endothelial-barrier may be considered as the main route for SARS-CoV-2 entry into the nervous system, with the barrier disruption being more logical than barrier permeability, as evidenced by postmortem analyses.

It has been a challenge to visualize in nature some concepts from abstract subjects such as mathematics and philosophy. Irrationality is certainly among the least comprehensive. This essay aimed to propose that irrationality is simply an illusion resulting from the human inability to grasp the full nature of reality, rather than actual continuity flaws in the fabric of existence. There are three major arguments: (1) human senses have limitations and these are likely to be extended to the intellect, (2) there are no observable existential discontinuities in everyday experience, and (3) some rational phenomena have irrational components. These arguments point towards the existence of a physical existence of irrational quantities or distances, visible to the human eye but not fully comprehended through arithmetic abstraction.

This case report describes evidence of intratubular biomineralization in root canal filled with calcium enriched material after 8 years of clinical maintenance. The schematic findings of dentinal tubules were investigated with scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). The root canal obturation material was closely adapted to root dentin surface, suggesting the possibility of chemical bonding between the two interfaces. SEM and EDS observation of dentinal tubules showed intratubular biomineralized crystal structures with Ca/P ratio in a range of 1.30–2.12, suggesting bioactive capacity of calcium enriched cement.

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

Zirconium based bulk metallic glasses are industrially valuable materials which commercial market grows rapidly. Surface modification of these metallic glasses by high-intensity lasers is relatively new and costly treatment promising great advantages over classical surface processing methods. In this work we perform the case study of surface modification of Zr$_{46}$Cu$_{36.8}$Ag$_{9.2}$Al$_8$ metallic glass by high-intensity millisecond laser beam. Our results suggest chemical deposition of atmospheric oxygen and nitrogen in the laser-melted surface area and its surroundings. Zirconium nitride layer was detected in the middle of laser-irradiated area. Nanocrystals embedded in the amorphous matrix were also formed on the surface. Overall, our findings suggest possibilities for improvement of mechanical characteristics of the studied metallic glass.

Hepcidin-25 was identified as the main iron regulator in the human body by binding to the sole iron-exporter ferroportin. Studies showed that the N-terminus of hepcidin is responsible for this interaction, the same N-terminus that encompasses a small copper(II)-binding site known as ATCUN (amino terminal Cu(II)- and Ni(II)- binding) motif. Interestingly, this copper-binding property is largely ignored in most papers dealing with hepcidin-25. In this context, detailed investigations of the formed complex of hepcidin-25 with copper could reveal insights into its biological role. The present work is mainly focused on the study of the metal-bound form of hepcidin-25, which could be considered the biologically active form. The first part is devoted to the reversed-phase chromatographic separation of copper-bound and copper-free hepcidin-25, which was achieved by applying basic mobile phases containing 0.1% ammonia. Further, mass spectrometry (tandem mass spectrometry MS/MS, high resolution mass spectrometry HRMS) and nuclear magnetic resonance (NMR) spectroscopy were employed to characterize the copper-peptide. Lastly, a 3D model of hepcidin-25 with bound copper(II) is presented. The identification of metal complexes and potential isoforms and isomers, from which the latter usually are left undetected by mass spectrometry, led to the conclusion that complementary analytical methods are needed to characterize a peptide calibrant or reference material comprehensively. Quantitative nuclear magnetic resonance (qNMR), inductively-coupled plasma mass spectrometry (ICP-MS), ion-mobility spectrometry (IMS) and chiral amino acid analysis (AAA) should be considered among others.

This paper describes a new approach that can be used to determine the mechanical properties of unknown materials and complex material systems. The approach uses inverse finite element modelling (FEM) accompanied with a designed algorithm to obtain the modulus of elasticity, yield stress and strain hardening material constants of an isotropic hardening material model, as well as the material constants of the Drucker-Prager material model (modulus of elasticity, cap yield stress and angle of friction). The algorithm automatically feeds the input material properties data to finite element software and automatically runs simulations to establish a convergence between the numerical loading-unloading curve and the target data obtained from continuous indentation tests using common indenter geometries. A further module was developed to optimise convergence using an inverse FEM analysis interfaced with a non-linear MATLAB algorithm. A sensitivity analysis determined that the dual Spherical and Berkovich (S&B) approach delivered better results than other dual indentation methods such as Berkovich and Vickers (B&V) and Vickers and Spherical (V&S). It was found that better convergence values can be achieved despite a large variation in the starting parameter values and / or material constitutive model and such behaviour reflects the uniqueness of the dual S&B indentation in predicting complex material systems. The study has shown that a robust optimization method based on a non-linear least-squares curve fitting function (LSQNONLIN) within MATLAB and ABAQUS can be used to accurately predict a unique set of elastic plastic material properties and Drucker-Prager material properties. This is of benefit to the scientific investigation of properties of new materials or obtaining the material properties at different location of a part which might be not be similar due to manufacturing processes (e.g. different heating and cooling rates at different locations).

Foam concrete is a construction material with controllable low strength and untraditional physical properties. Its highly crushable nature leaves it a niche as an engineered energy-absorbing material in many value-added applications; however, fundamental understanding of the material properties is crucial. As foam concrete is highly cellularized and ductile, conventional concrete testing methods such as compression test are insufficient to characterize the key material attributes of foam concrete, especially when the foam density is low. The resonant frequency test (ASTM C215) is specified for evaluating dynamic Young’s modulus of normal concrete. Inspired by the non-destructive feature of this test, we investigate the possibility of using the resonant frequency test to continuously monitor the modulus build-up of foam concrete with age. For the representativeness of the samples, three variables are considered in material design—bulk density ranging from 0.4 to 1.2 g/cm3, water to cementitious materials ratio of 0.42 and 0.47, and fly ash replacement of 10 and 30% by weight of cement. After examining the different vibration modes, the fundamental transverse frequency is determined most suitable for interpreting the foam modulus. The experimental results demonstrate good accuracy of using this approach for the measurement of different samples. It is also confirmed that, for a given foam concrete, the foam modulus can be predicted by knowing the foam density and solid modulus of its base cement paste, which provides an important insight for the further studies and real applications of foam concrete.

We report on the development of chemical vapour deposition (CVD) based graphene field effect transistor (GFET) immunosensors for the sensitive detection of Human Chorionic Gonadotropin (hCG), a glycoprotein risk biomarker of certain cancers. The GFET sensors were fabricated on Si/SiO₂ substrate using photolithography with evaporated chromium and sputtered gold contacts. GFET channels were functionalized with a linker molecule to immobile anti-hCG antibody on the surface of graphene. Binding reaction of the antibody with varying concentration levels of hCG antigen demonstrated the limit of detection of the GFET sensors to be below 1 pg/mL using four-probe electrical measurements. We also show annealing can significantly improve the carrier transport properties of GFETs and shift the Dirac point (Fermi level) with reduced p-doping in back-gated measurements. The developed GFET biosensors are generic and could find applications in a broad range of medical diagnostics in addition to cancer, such as neurodegenerative (Alzheimer’s, Parkinson’s and Lewy body) and cardiovascular disorders.

A distinctive feature of the SARS-CoV-2 spike protein is its ability to efficiently fuse cells, thus producing syncytia found in COVID-19 patients. This commentary proposes how this ability enables spike to cause COVID-19 complications as well as side effects of COVID-19 vaccines, and suggests how these effects can be prevented..

The unique porous crystal structure of zeolite offers various important utilizations, it is one of the considerations in selecting zeolite at this study as component of composite for restraining noise. It so happens, previous experiments show that banana stem has porous structure, fibrous, high flexibility and can be applied as material for many various products including as component of acoustic material. The combination of both is alleged that it has capability in absorbing noise. This paper presents an investigation on the composite that it was synthesized of Activated Zeolite and Banana Stem Fibre in various weight for determining its sound absorption coefficient alpha (a). Activating natural zeolite was conducted by using 6M HCl in order for enlarging zeolite pores. The sound absorption coefficient was measured in the frequency range between 125 Hz up to 6000 Hz. The results show that the different weight of banana stem fibre as component of the synthesized composite affects the value of alpha and shifts the frequency area.

In this study is reported the optical, structural and dielectric properties of Poly (vinyl alcohol) thin films membranes with embedded ZnO nanoparticles (PVA/ZnO) obtained by solution casting method at low temperature of deposition. Fourier Transform Infrared spectra showed the characteristics peaks, which correspond to O-H and Zn-O bonds present in the hybrid material. The X-ray diffraction patterns indicated the presence of ZnO structure into the films. The composite material showed low absorbance and a wide band gap energy from 5.6 to 5.9 eV. The surface morphology for the thin films of PVA/ZnO was studied by Atomic Force Microscopy and Scanning Electron Microscopy. The dielectric properties of the nanocomposites were measured from low to high frequencies, the results showed a high dielectric constant (ε) in the order of 10⁴ at low frequency and values from ε ≈ 2000 to 100 in the range of 1KHz-1MHz respectively, the properties of PVA/ZnO such as the high permittivity and the low temperature of processing make it a suitable material for potential applications in the development of flexible electronic devices.

In the last three decades, the robust scientific data emerged, demonstrating that the immune-inflammatory response is a fundamental component of the pathophysiology of major depressive disorder (MDD). Psychological stress and various inflammatory comorbidities contribute to such immune activation. Still, this is not uncommon that patients with depression do not have defined inflammatory comorbidities, and alternative mechanisms of immune activation need to take place. The gastrointestinal (GI) tract, along with gut-associated lymphoid tissue (GALT), constitutes the largest lymphatic organ in the human body and forms the biggest surface of contact with the external environment. It is also the most significant source of bacterial and food-derived antigenic material. There is a broad range of reciprocal interactions between the GI tract, intestinal microbiota, increased intestinal permeability, activation of immune-inflammatory response, and the CNS that has crucial implications in brain function and mental health. This intercommunication takes place within the microbiota-gut-immune-glia (MGIG) axis, and glial cells are the main orchestrator of this communication. A broad range of factors, including psychological stress, inflammation, dysbiosis and other, may compromise the permeability of this barrier. This leads to excessive bacterial translocation and the excessive influx of food-derived antigenic material that contributes to activation of the immune-inflammatory response and depressive psychopathology. This chapter summarizes the role of increased intestinal permeability in MDD and mechanisms of how the "leaky gut" may contribute to immune-inflammatory response in this disorder.

The shape memory alloys belong to the smart materials thanks to their thermomechanical proprieties' reply to thermal or to mechanical loading. These materials can change shape, stiffness, displacement, natural frequency, and many mechanical characteristics in response to stress or to heat such as conduction, convection or radiation. However, heating by convection or conduction are the most useful and studied methods unlike radiation. Therefore, this paper aims to study the radiation effect on the shape memory alloy behavior

FoxP3 is a transcription factor essential for the differentiation and function of T regulatory cells (Tregs). There are two major subsets of Tregs: natural Tregs (nTregs) generated in thymus and inducible Tregs (iTregs) produced in peripheral immune system. It has been documented that iTreg development is dependent on soluble mediators including interleukin 2 (IL2), transforming growth factor β (TGFβ) and all-trans-retinoic acid (ATRA). In our experiments we performed a gene expression array, followed by Real-time PCR experiments, to study the expression of genes regulated by 1,25-dihydroxyvitamin D (1,25D) or ATRA in cells of myeloid origin. Our experiments revealed that ATRA alone, but also a cocktail of mediators consisting of IL2, TGFβ and ATRA, upregulate the expression of FOXP3 gene in lymphoid cells, but also in normal and leukemic myeloid cells. The FoxP3 expression is followed by a phenotypic changes in cells of myeloid origin. Our results indicate that signaling pathways which are used in the late stages of T cell differentiation, are also active in the cells of myeloid lineage

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

Material efficiency is a key element of new thinking to address the challenges of reducing impacts on the environment and of resource scarcity, whilst at the same time meeting service and functionality demands on materials. Directly related to material efficiency is the concept of the Circular Economy, which is based on the principle of optimising the utility embodied in materials and products through the life cycle. Whilst steel, as a result of high recycling rates, is one of the most ‘circular’ of all manufactured materials, significant opportunities for greater material efficiency exist, which are yet to be widely implemented. In the field of Life Cycle Management, Life Cycle Assessment (LCA) is commonly used to assess the environmental benefits of recovering and recycling materials through the manufacturing supply chain and at end-of-life. As well as containing information to calculate environmental impacts, LCA models also provide the flows of materials through the product life cycle and can also be used to quantify material efficiency and the circularity of a product system. Using an example taken from renewable energy generation, this paper explores the correlation between product circularity and the environmental case for strategies designed to improve material efficiency. An LCA-based methodology for accounting for the recovery and re-use of materials from the supply chain, and at end-of-life, is used as the basis for calculating the carbon footprint benefits of five material efficiency scenarios. Resulting carbon footprints were then compared with a number of proposed material circularity indicators. Two conclusions from this exercise were that i) LCA methodologies based around end-of-life approaches are well placed for quantifying the environmental benefits of material efficiency and circular economy strategies and ii) when applying indicators relating to the circularity of materials these should also be supported by LCA studies.

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.

Antigen-based rapid diagnostic tests for Lymphatic filariasis do not come with quality control (QC) materials, and research and disease control programmes rely on stored positive plasma samples. This study was undertaken to evaluate the use of freeze-dried Wuchereria bancrofti antigen positive plasma samples to serve as QC materials for LF RDTs. 10 well characterized W. bancrofti positive samples were lyophilized and stored at 4°C, 28°C and 40°C. The samples were evaluated using the Filaria Test Strips before lyophilization and after one and three (3) months of storage. The sensitivity and stability of the lyophilized samples were evaluated. The results revealed a loss of sensitivity and stability with increasing temperature and duration of storage. The results are further discussed in terms of the use of Dried Blood Spot (DBS) in diagnostics studies on LF requiring quantitative assessments, and the need for thoughtful DBS preparation and storage.

Hypertension is a common and growing medical problem that leads to enormous cardiovascular and kidney disease worldwide. While many drugs exist to treat hypertension, there is large individual variation in how a given individual responds to different agents, which contributes to dismal rates of hypertension control. While demographic factors predict which drugs may work better in certain individuals, a great degree of this variation has a genetic basis. In recent years, genome wide association studies have begun to identify specific gene variants that predict drug response to particular agents. This review identifies the major genetic variants influencing antihypertensive response that have emerged from this growing body of work. For novel genetic variants without a previously known biologic basis in blood pressure, it is crucial to validate initial findings in subsequent studies. This information may eventually lead to a more personalized approach to hypertension management that will improve blood pressure control and patient outcomes. The integration of this large amount of data and its real world application will be highly challenging, but strategies to accomplish this are discussed.

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

Foam concrete is a highly cellularized cementitious material that undergoes extensive plastic deformation when loaded to failure. Under compression, the foam structure gets progressively crushed at a steady stress stage such that a substantial amount of energy is dissipated. Understanding foam concrete crushing behavior is of special importance for its engineering applications such as energy absorber, but the current studies are insufficient to define material properties for design of field applications. This study characterizes the crushing strength and foam modulus of samples with penetration test and resonant frequency test, respectively. A four-phase crushing behavior is observed. The yield strength and plateau strength are identified to characterize the foam crushing. Using the experimental inputs, the modulus-strength constitutive equations are then established. These findings are useful for expanding the knowledge of normal concrete to studies on foam concrete, as well as design of applications.Foam concrete is a highly cellularized cementitious material that undergoes extensive plastic deformation when loaded to failure. Under compression, the foam structure gets progressively crushed at a steady stress stage such that a substantial amount of energy is dissipated. Understanding foam concrete crushing behavior is of special importance for its engineering applications such as energy absorber, but the current studies are insufficient to define material properties for design of field applications. This study characterizes the crushing strength and foam modulus of samples with penetration test and resonant frequency test, respectively. A four-phase crushing behavior is observed. The yield strength and plateau strength are identified to characterize the foam crushing. Using the experimental inputs, the modulus-strength constitutive equations are then established. These findings are useful for expanding the knowledge of normal concrete to studies on foam concrete, as well as design of applications.

Water splitting plays an important role in electrochemical and photoelectrochemical conversion of energy devices. Electrochemical water splitting by the hydrogen evolution reaction (HER) is a straightforward route to produce hydrogen (H2), which requires an efficient electrocatalysts to minimize energy consumption. Recent advances have created a rapid rise in new electrocatalysts, particularly those based on non-precious metals. In this review, we present a comprehensive overview of the recent developments of ternary and quaternary 6d-group transition metal chalcogenides (TMCs) based electrocatalysts for water splitting, especially for HER. Detailed discussion is organized from binary to quaternary TMCs including, surface engineering, heterostructures, chalcogen substitutions, and hierarchically structural design in TMCs. Moreover, emphasis is placed on future research scope and important challenges facing these electrocatalysts for further development in their performance towards water splitting.

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

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.

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

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.

Very little is known about laboratory confirmed blood stream infections (LCBIs) in neonatal intensive care units (NICUs) in resource-limited settings. The aim of this cohort study was to determine the incidence, risk factors, and causative agents of LCBIs in a level-2 NICU in India. The diagnosis of LCBIs was established using the Centre for Disease Control, USA criteria. A predesigned questionnaire containing risk factors associated with LCBIs was filled-in. A total of 150 neonates (43% preterm) were included in the study. The overall incidence of LCBIs was 31%. The independent risk factors for LCBIs were: preterm neonates (relative risk (RR) 2.23), duration of NICU stay more than 14 days (RR 1.75), chorioamnionitis in the mother (RR 3.18), premature rupture of membrane in mothers (RR 2.32), neonate born through meconium-stained amniotic fluid (RR 2.32), malpresentation (RR 3.05), endotracheal intubation (RR 3.41), umbilical catheterization (RR 4.18), and ventilator-associated pneumonia (RR 3.17). The initiation of minimal enteral nutrition was protective from LCBIs (RR 0.22). The predominant causative organisms were gram-negative pathogens (58%). The results of the present study can be used to design antibiotic interventions to reduce LCBIs in resource-limited settings.

The Siret River crosses NE Romania from the north to the south and it discharges into the Danube, near the city of Galati. During the period, 17^th June - 10^th July 2010, significant amounts of precipitations in the mountainous basin of Siret were recorded. The floods comprised two periods with four bimodal cycles and they were counted among the strongest on the Romanian territory. The exceptional floods occurred in the rivers of Siret, Suceava, Moldova, Bistrita, Trotus and so on. The most important compound flood wave was determined by the precipitations which fell within the period, 29^th June to 1^st July 2010, when significant amounts of rain were recorded, sometimes, exceeding 80 mm. The high discharges on the Bistrita River – downstream from the Bicaz Reservoir – were controlled by complex hydro technical works. The maximum discharge for the year 2010 summer floods was recorded at Dragesti hydrometric station: 2,884 m³/s (historic discharge) compared to the preceding historic discharge of the year 2008 (2,850 m³/s). The effects of floods were strongest in the counties of Suceava, Neamt, and Bacau. The floods on the main course of the Siret River were analyzed in correlation with the tributaries within the mountainous sector.

Enzyme replacement therapy (ERT) improves the somatic manifestations in mucopolysaccharidoses (MPS))．However, because intravenously administered enzymes cannot cross the blood brain barrier (BBB), ERT is ineffective against the progressive neurodegeneration and resultant severe central nervous system (CNS) symptoms observed in patients with neuronopathic MPS. Attempts to surmount this problem have been made with intrathecal and intracerebroventricular ERT intend to achieve CNS effects, but the burdens on patients are inimical to long-term multiple administrations. However, after pabinafusp alfa, a human iduronate-2-sulfatase fused with a BBB-crossing anti-transferrin receptor antibody, showed both central and peripheral efficacy in mice model, subsequent clinical trials in a total of 62 patients with MPS-II (Hunter syndrome) in Japan and Brazil substantiated this dual efficacy and provided an acceptable safety profile. To date, pabinafusp alfa is the only approved intravenous ERT effective against both the somatic and CNS symptoms of patients with MPS-II. This article summarizes the hitherto obtained preclinical and clinical evidence associated with this drug, and discusses the preclinical, translational and clinical challenges of evaluating, ameliorating and preventing the neurodegeneration in patients with MPS-II.

The authors determined mass concentrations of 12 elements (As, Cd, Cr, Cu, Mn, Ni, Pb, Se, Sr, Tl, V, Zn) in blood and urine taken from 100 rural children living in unremarkable condition in the West Ural region of the Russian Federation. We applied inductively coupled plasma mass spectrometry in conformity with Methodical Guidelines 4.1. 3230-14 (FR.1.31.2014.17064) designed by us and detailed in the paper. The article contains setting parameters for Agilent 7500cx quadrupole inductively coupled plasma mass spectrometer . The authors present grounds for an optimal scheme of samples preparation which helps to eliminate "matrix" effect and explain why it is advisable to use reaction/collision functioning mode as it enables interference overlaps suppression.To prepare whole blood samples for analysis, we used acid dissolution in concentrated nitric acid followed by centrifugation. The arithmetic mean (AM) of element content in blood amounted to 0.34 µg/l (As); 0.39 µg/l (Cd); 6.41 µg/l (Cr); 866.11 µg/l (Сu); 13.73 µg/l (Mn); 5.86 µg/l (Ni); 23.65 µg/l (Pb); 87.43 µg/l (Se); 33.54 µg/l (Sr); 0.04 µg/l (Tl); 0.16 µg/l (V); 4713.48 µg/l (Zn). The validity of the results was confirmed by means of SERONORM ^TM Whole Blood L2 standard samples (Norway). Urine samples were directly analyzed after 1/10 (V/V) dilution with 1% nitric acid solution. The arithmetic mean of element content of urine corresponded to 18.99 µg/l (As); 0.12 µg/l (Cd); 1.91 µg/l (Cr); 13.28 µg/l (Сu); 0.96 µg/l (Mn); 1.84 µg/l (Ni); 0.83 µg/l (Pb); 22.55 µg/l (Se); 239.09 µg/l (Sr); 0.16 µg/l (Tl); 0.68 µg/l (V); 270.56 µg/l (Zn). The validity of the results was confirmed by analyzing the SERONORM ^TM standard urine samples (Norway). Regional differences from levels found in other countries included higher concentrations of Cr, Mn and Ni in blood and lower levels of Se and Zn levels in West Ural children. Urine concentrations of West Ural children showed higher levels of As and Sr.

A non-Newtonian fluid model is used to investigate the two-dimensional pulsatile blood flow through a tapered artery with a stenosis. The mixed convection effects of heat and mass transfer are also taken into account. By applying non-dimensionalization and radial coordinate transformation, we simplify the system in a tube. Under the finite difference scheme, numerical solutions are calculated for velocity, temperature concentration, resistance, impedance, wall shear stress and shearing stress at the stenosis throat. Finally, Quantitative analysis is carried out.

Ultrafast laser 3D lithography based on non-linear light-matter interactions, widely known as multi-photon lithography (MPL), offers unrivaled precision rapid prototyping and flexible additive manufacturing options. 3D printing equipment based on MPL are already commercially available, yet there is still no comprehensive understanding of factors determining spatial resolution, accuracy, fabrication throughput, repeatability, and standardized metrology methods for the accurate characterization of the produced 3D objects and their functionalities. The photoexcitation mechanisms, spatial-control or photo-modified volumes, and the variety of processable materials are topics actively investigated. The complexity of the research field is underlined by limited understanding and fragmented knowledge of light-excitation and material response. Research to date has only provided case-specific findings on photoexcitation, chemical modification, and material characterization of the experimental data. In this review, we aim to provide a consistent and comprehensive summary of the existing literature on photopolymerization mechanisms under highly confined spatial and temporal conditions, where, besides the excitation and cross-linking, parameters such as diffusion, temperature accumulation, and the finite amount of monomer molecules start to become of critical importance. Key parameters such as, photoexcitation, polymerization kinetics, and the properties of the additively manufactured materials at the nanoscale in 3D are examined, whereas, the perspectives for future research and as well as emerging applications are outlined.

Over past decades, a frequent co-morbidity of cerebrovascular pathology and Alzheimer's disease pathology has been observed. Numerous published studies indicate that preservation of healthy cerebrovascular endothelium can be an important therapeutic target. By incorporating appropriate drug(s) into biomimetic (lipid cubic-phase) nanocarriers, one obtains a multitasking combination therapeutic which targets certain cell-surface scavenger receptors, mainly class B type 1 (i.e., SR-BI), and crosses the blood-brain barrier. This targeting allows for various Alzheimer’s-related cell types to be simultaneously searched out for localized drug treatment in vivo.

Patients with schizophrenia (SCZ) are at high risk of cardiovascular disease (CVD) due to an inherited predisposition, a sedentary life style and the use of antipsychotic medications. Several approaches have been taken to minimize this risk but results continue to be unsatisfactory. A potential alternative is prescribing Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs decrease platelet aggregation and reduce the risk of coronary heart disease in patients with depression. We therefore aim to investigate whether there is evidence that supports the use of SSRIs to reduce the risk for CVD in SCZ. A systematic review of the literature revealed five published reports relating to the impact of SSRIs on CV risk in SCZ. Three trials assessed the influence on metabolic parameters of fluvoxamine when combined with clozapine. Two of those studies found improvements with fluvoxamine. Of the other two reports, one indicates SSRIs as a group caused minimal but statistically significant increments in total cholesterol, LDL and triglyceride. The second report suggests that when SSRIs are combined with antipsychotics, the metabolic impact depends on the antipsychotic prescribed. While there are promising results, further studies are needed to establish the impact of SSRIs on CV risk in SCZ.

Multi-Alignment method coupled with phylogenetic analysis we disclosed the Nsp9 and Nsp10 non-structural proteins of Corona Virus as rRNA RlmH/K methyltransferases with similarities with bin recombinase and int-core integrase fold. Further, Nsp9 has similarities to S8 ribosomal protein and Nap10 has similarity to S10 ribosomal protein. Previously, we showed Nsp13, Nsp14, Nsp15 and Nsp16 are also different types of rRNA RlmE/N and Cfr-like methyltransferases-ribonuclease with RNA helicase domains. Two domains of Nsp13 astonishingly have similarities to ribosomal proteins L6 and L9. Taken together, Nsp9/10 and Nsp13-16 proteins could mimic host ribosome assembly and also could methylate rRNA of mitobibosome preventing mitochondrial protein synthesis and oxidative phosphorylation. Low ATP synthesis causes lowering blood pressure following coma but very ATP concentration (1-10nM) surely induces platelets aggregation through vWA, collagen and GpIIb/IIIa proteins followed by fibrin formation and blood clotting as recently have seen in the lung of many Corona virus infected patients. We have also postulated that two polyproteins itself resemble like 28S and 38S mitoribosome subunits and compete with rRNAs inhibiting the ribosome turnover and new protein synthesis due to their similarities with many ribosomal proteins. Such finding may be valuable in computer-based novel drug design against Corona virus.

Most of the phase change materials (PCMs) have been limited to use as functional additions or sealed in containers, and extra auxiliary equipment or supporting matrix is needed. The emergence of 3D printing technique has dramatically advanced the developments of materials and simplified production processes. This study focuses on a novel strategy to model thermal energy storage crystalline gels with three-dimensional architecture directly from liquid resin without supporting materials through light-induced polymerization 3D printing technique. A mask-projection stereolithography printer was used to measure the 3D printing test, and the printable characters of crystalline thermal energy storage P(SA-DMAA) gels with different molar ratios were evaluated. For the P(SA-DMMA) gels with small fraction of SA, the 3D fabrication was realized with higher printing precision both on mili- and micro-meter scales. As a comparison of 3D printed samples, P(SA-DMAA) gels made by other two methods, post-UV curing treatment after 3D printing and UV curing using conventional mold, were prepared. The 3D printed P(SA-DMAA) gels shown high crystallinity. Post–UV curing treatment was beneficial to full curing of 3D printed gels, but did not lead to the further improvement of crystal structure to get higher crystallinity. The P(SA-DMAA) crystalline gel having the highest energy storage enthalpy that reached 69.6 J·g⁻¹ was developed. Its good thermoregulation property in the temperature range from 25 to 40 °C was proved. The P(SA-DMAA) gels are feasible for practical applications as one kind of 3D printing material with thermal energy storage and thermoregulation functionality.

Carbonous nanomaterials are promising additives for composite coatings for heat-dissipation materials because of their excellent thermal conductivity. Here, copper/carbonous nanomaterial composite coatings were prepared using nanodiamond (ND) as the carbonous nanomaterial. The copper/ND composite coatings were electrically deposited onto copper substrates from a continuously stirred copper sulfate coating bath containing NDs. NDs were dispersed by ultrasonic treatment, and the initial bath pH was adjusted by adding sodium hydroxide solution or sulfuric acid solution before electrodeposition. The effects of various coating conditions—the initial ND concentration, initial bath pH, stirring speed, electrical current density, and the amount of electricity—on the ND content of the coatings were investigated. Furthermore, the surface of the NDs was modified by hydrothermal treatment to improve ND incorporation. A higher initial ND concentration and a higher stirring speed increased the ND content of the coatings, whereas a higher initial bath pH and a greater amount of electricity decreased it. The electrical current density showed a minimum ND content at approximately 5 A/dm². Hydrothermal treatment, which introduced carboxyl groups onto the ND surface, improved the ND content of the coatings. A copper/ND composite coating with a maximum of 3.85 mass% ND was obtained.

Background: Selection and application of suture materials, has gained more importance especially with the increasing number of patients seeking oral surgeries. Since lying in a bacterial-filled environment, sutures make the tissue prone to infection. Suture material plays an important role in the reduction of the risk of infection. This study aimed to assess the success rate of an antibacterial suture named Vicryl Plus in preventing bacterial growth in the surgical site of the mandibular third molar. Methods: 27 patients were included in this double-blinded randomized clinical trial study. Surgical Extraction of the mandibular wisdom tooth was done and the incision was managed by randomly using Vicryl Plus and Vicryl sutures. After 7 days, sutures were removed and assessed microbiologically. Predominant species of Streptococcus mutans and Lactobacillus were assessed as well as the total number of colonies on each suture. Results: There was a significant difference between two suture materials in colony number-length ratio of lactobacillus (p-value= 0.031) and total bacterial colonies (p-value=0.016); but not for S. mutans species (p-value=0.201). Conclusion: Antibacterial Vicryl suture can be a useful tool for the reduction in the rate of surgical site infection in high-risk cases and situations.

3D-printing with foam concrete, which is known for its distinct physical and mechanical properties, has not yet been purposefully investigated. The article at hand presents a methodological approach for the mixture design of 3D-printable foam concretes and a systematic investigation of the potential application of this type of material in digital construction. Three different foam concrete compositions with water-to-binder ratios between 0.33 and 0.36 and having densities of 1100 to 1580 kg/m³ in the fresh state were produced with a pre-foaming technique using a protein-based foaming agent. Based on the fresh-state tests, including 3D-printing as such, an optimum composition was identified and its compressive and flexural strengths were characterised. The printable foam concrete showed compressive strength above 10 MPa and low thermal conductivity, which make it suitable for 3D-printing applications, while fulfilling both load-carrying and insulating functions.

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

One century ago, ferroelectricity and then piezoelectricity were discovered using Rochelle salt crystals. Today, modern societies are invited to switch towards a resilient and circular economy model. In this context, this work proposes a method to manufacture piezoelectric devices made from agro-resources such as tartric acid and polylactide significantly reducing the energy budget without requiring any sophisticated equipement. These piezoelectric devices are manufactured by liquid phase epitaxy grown Rochelle salt (RS) crystals into a 3D printed poly(Lactic acid) (PLA) matrix being the artificial squared meshes which mimic the natural wood anatomy. This composite material can easily be produced in any fablab with renewable materials and at low processsing temperatures, reducing then the total energy consumed. Manufactured biodegradable samples are fully recyclable and have good piezoelectric properties without any pooling step. The measured piezoelectric coefficients of manufactured samples are higher than many piezoelectric polymers such as PVDF-TrFE.

Oscillometric blood pressure (BP) devices currently estimate a single point but do not identify fluctuations in BP or distinguish them from variations in response to physiological properties. In this paper, to analyze BP normality based on oscillometric measurements, we use statistical approaches including kurtosis, skewness, Kolmogorov-Smirnov, and correlation tests. Then, to mitigate uncertainties, we use a deep neural network (DNN) to determine the confidence limits (CLs) of BP measurements based on their normality. The proposed DNN regression model decreases the standard deviation of error (SDE) of the mean error (ME) and the mean absolute error (MAE) and reduces the uncertainty of the CLs and SDEs of the proposed technique. We validate the normality of the distribution of the BP estimation distribution which fits the Gaussian distribution very well. We use a rank test in the DNN regression model to demonstrate the independence of the artificial SBP and DBP estimations. First, we perform statistical tests to verify the normality of the BP measurements for individual subjects. The proposed methodology provides accurate BP estimations and reduces the uncertainties associated with the CLs and SDEs based on the DNN regression estimator.

Finely ground glass has the potential for pozzolanic reactivity and can serve as a supplementary cementitious material (SCM). Glass reaction kinetics depends on both temperature and glass composition. Microstructural modeling is a helpful approach to get better understanding of cement hydration and microstructure development. Mechanical and performance properties of concrete are directly related to the development of concrete microstructure, which is the consequence of progress in cement hydration. This study initially provides a comprehensive background about cement hydration process and microstructural modeling of the hydration. It then utilizes results of experimental studies, i.e. isothermal calorimetry and thermogravimetric analysis, to find kinetics equation parameters called “Avrami Constants”. For the first time, these constants were found for three main components of cement, i.e. C₃S, C₂S, and C₃A, and also for glass particles smaller than 25 µm. Although modeling of cement hydration and cementitious systems containing single glass particles showed promising results, simulations of combined glass types and sizes showed that more work on microstructural models is needed to properly model the reactivity of mixed glass particle systems.

Stroke remains a major cause of death and disability in the United States and around the world. Solid safety and efficacy profiles of novel stroke therapeutics have been generated in the laboratory, but most failed in clinical trials. Investigations into the pathology and treatment of the disease remain a key research endeavor in advancing scientific understanding and clinical applications. In particular, cell-based regenerative medicine, specifically stem cells transplantation, may hold promise as stroke therapy because grafted cells and their components may recapitulate the growth and function of the neurovascular unit, which arguably represents the alpha and omega of stroke brain pathology and recovery. Recent evidence has implicated mitochondria, organelles with a central role in energy metabolism and stress response, in stroke progression. Recognizing that stem cells offer a source of healthy mitochondria, potentially transferrable into ischemic cells, may provide a new therapeutic tool. To this end, deciphering cellular and molecular processes underlying dysfunctional mitochondria may reveal innovative strategies for stroke therapy. Here, we review recent studies capturing the intimate participation of mitochondrial impairment in stroke pathology, and showcase promising methods of healthy mitochondria transfer into ischemic cells, to critically evaluate the potential of mitochondria-based stem cell therapy for stroke.

Plasma and serum are the most widely used blood-derived biofluids for metabolomics and lipidomics assays, but the isolation of these products from blood may introduce additional bias as indicated by the fact that many analytes that are present at high concentrations in blood cells cannot be measured and evaluated in those samples. Of particular concern, variable hemolysis during the pre-processing of blood products could compromise accurate and reproducible quantification. Compared with plasma or serum, whole blood may be a better alternative due to simplicity of processing. In this study, we provide a comprehensive method for quantification of the whole blood sphingolipidome and the concentrations were compared with those from plasma. Combining a single-phase extraction method with liquid-chromatography high resolution mass spectrometry (R=120, 000), assisted by alkaline hydrolysis, we were able to identify and simultaneously quantify more than 150 sphingolipids. Furthermore, most of sphingolipids remained stable after a freeze/thaw cycle. Whole blood contained a higher concentration of most sphingolipids than corresponding plasma. Moreover, individual variations in the levels of sphingolipids were lower for whole blood than plasma. These findings demonstrate that whole blood could be a better alternative to plasma, and potentially guide the evaluation of sphinglipidome for biomarker discovery.

The present work deals with the development of finite element methodology for obtaining the stress distributions in thick cylindrical HK40 stainless steel pipe that carry high temperature fluids. The material properties and loading are assumed to be random variables. Thermal stresses that are generated along radial, axial and tangential directions are computed generally using analytical expressions which are very complex. To circumvent such an issue, the probability theory and mathematical statistics have been applied to many engineering problems which allows to determine the safety both quantitatively and objectively based on the concepts of reliability. Monte Carlo simulation methodology is used to study the probabilistic characteristics of thermal stresses which is used for estimating the probabilistic distributions of stresses against the variations arising due to material properties and load. A 2-D Probabilistic finite element code is developed in MATLAB and the deterministic solution is compared with ABAQUS solutions. The values of stresses that are obtained from the variation of elastic modulus are found to be low as compared to the case where the load alone is varying. The probability of failure of the pipe structure is predicted against the variations in internal pressure and thermal gradient. These finite element framework developments are useful for the life estimation of piping structures in high temperature applications and subsequently quantifying the uncertainties in loading and material properties.

The acetylcholinesterase (AChE) inhibitors are the main drugs for symptomatic treatment of neurodegenerative disorders like Alzheimer’s disease. A recently designed, synthesized and tested hybrid compound between the AChE inhibitor galantamine (GAL) and the antioxidant polyphenol curcumin (CU) showed high AChE inhibition in vitro. Here, we describe tests for acute and short-term toxicity in mice as well as antioxidant tests on brain homogenates measured the levels of malondialdehide (MDA) and glutathione (GSH). Haematological and serum biochemical analyses were also performed. In the acute toxicity tests, the novel AChE inhibitor given orally in mice showed LD50 of 49 mg/kg. The short-term administration of 2.5 and 5 mg/kg did not show toxicity. In the ex vivo tests, the GAL-CU hybrid performed better than GAL and CU themselves. In a dose of 5 mg/kg, it demonstrates 25% reduction in AChE activity, 28% and 73% increase in the levels of MDA and GSH, respectively. No significant changes in blood biochemical data were observed. The GAL-CU hybrid is a novel non-toxic AChE inhibitor with high antioxidant activity which makes it a perspective multitarget drug candidate for treatment of Alzheimer’s disease.

The present work shows a novel physical-mathematical model to estimate the average corrosion resistance index from the crystallographic texture in API 5L steels. The crystallographic texture of the studied steels was measured by means of the X-ray diffraction technique. The model, based on the symmetric spherical surface harmonics for a BCC structure, is capable of describing the anisotropy surface of anodic dissolution resistance of the crystal and establishing a straightforward relationship between crystallographic texture, surface roughness, and metal corrosion behavior. The predictions of the average corrosion resistance index made from the crystallographic texture were in good agreement with those obtained from potentiodynamic polarization curves for the investigated steels. This agreement validates the capacity of this model and opens the possibility of applying it as a novel criterion for the material selection and design stages in order to combat metal corrosion problems.

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

Artificial reefs have been deployed in multiple regions of the world for different purposes including habitat restoration and protection, biodiversity and fish stock enhancement, fisheries management and recreation. Artificial reefs can be a valuable tool for ecosystem protection and rehabilitation, helping mitigate the effects of anthropogenic impacts that we face today. However, knowledge on artificial reefs is unevenly distributed worldwide, with some regions having much more quality information available and published (e.g. European Mediterranean Sea area), while others, for instance the North-East Atlantic area, do not. Here, we provide a characterization of purposely built artificial reefs in North-East Atlantic area based on all available literature (i.e. research papers and reports), highlighting the needs and gaps that are vital for establishing future perspectives for artificial reef deployment and research. In the North-East Atlantic area, sixty-one purposely built artificial reefs have been deployed since 1970, mostly between the years 1990-2009, with Spain being the country with the highest number of artificial reefs. The most reported purpose for their deployment is fisheries productivity and habitat/species protection, although, most artificial reefs are multipurpose in order to maximise the benefits of a given financial investment. The majority of artificial reefs were submerged at < 50 m, mainly between 10-20 m of depth. The most used designs were cubic blocks and complex designs made by an array of combined shapes, which mostly consist of concrete (79%). From all the analysed data on artificial reefs, 67% of the cases reported surveys to assess biodiversity after the deployment. However, in 26% of those cases, data was not available. When data was available, only 31% of cases reported long-term biomonitoring surveys (3 years or more). Based upon these findings, we noticed a general lack of scientifically robust data, including records of species and abundance of both fish and invertebrates, as well as macroalgae. Preventing an adequate determination of the best balance between shape, construction material and bio-colonization. Critiques and suggestions are discussed in the light of current available data in order to perform more efficient research, evaluation and functioning of future artificial reefs.

Thermal interface material (TIM) that can exist as liquid at the service temperature enables efficient heat transfer across two adjacent surfaces in electronic applications. In this work, the thermal conductivities of different phase regions in the Ga-In system at various compositions and temperatures are measured for the first time. A modified comparative cut bar technique is used for the measurement of the thermal conductivities of In_xGa_1-x (x=0, 0.1, 0.214, 0.3, and 0.9) alloys at 40, 60, 80, and 100^oC that are the temperatures commonly encountered in consumer electronics. The thermal conductivity values for the liquid and semi-liquid (liquid+β) Ga-In alloys are higher than the TIM currently used in consumer electronics. These measured quantities, along with the available experimental data from the literature, served as input for the thermal conductivity parameter optimization using the CALPHAD (CALculation of PHase Diagram) method for the pure elements, solution phase, and two-phase region. A set of self-consistent parameters for the description of the thermal conductivity of the Ga-In system is obtained. There is good agreement between the measured and calculated thermal conductivity values for all the phases. Hence, it can be envisaged that liquid/semi-liquid Ga-In alloys can be considered as a potential TIM in consumer electronics due to its high thermal conductivity.

The main neurovascular unit of the Blood Brain Barrier (BBB) consists of a cellular component, which includes endothelial cells, astrocytes, pericytes, microglia, neurons and oligodendrocytes, as well as a non-cellular component resulting from the extracellular matrix. The endothelial cells are the major vital component of the BBB able to preserve the brain homeostasis; these cells are situated along the demarcation line between the bloodstream and the brain. Therefore, an alteration or the progressive disruption of the endothelial layer may clearly impair the brain homeostasis. The proper functioning of the brain endothelial cells is generally ensured by two elements: 1) the presence of junction proteins; 2) the preservation of a specific polarity involving an apical-luminal and a basolateral-abluminal membrane. In view of the above, this review intends to identify the molecular mechanisms underlying BBB function and their changes occurring in early stages of neurodegenerative processes in order to develop novel therapeutic strategies aimed to counteract neurodegenerative disorders.

A progressive FEA fatigue degradation model for composites was developed and implemented using a UMAT user material subroutine in Abaqus. Numerical results were compared to experimental strain field data from high frequency Digital Image Correlation (DIC) of split disk fatigue testing of pressure vessel cut outs with holes. The model correctly predicted the onset and evolution of damage in the matrix as well as the onset of fiber failure. The model use progressive failure analysis based on the maximum strain failure criterion, the cycle jump method and Miner sum damage accumulation rule. A parameter study on matrix properties was needed to capture the scatter in strain fields observed experimentally by DIC. S-N curve for the matrix material had to be lowered by 0% to 60% to capture the experimental scatter. The onset of local fiber failure had to be described by local S-N curves measured by DIC having 2.5 times greater strain than that of S-N curves found from standard coupon testing.

Heating films were prepared by using poly(methyl methacrylate) and polybutadiene composites containing graphite. The heating film was prepared by casting the as-made polymer composite on PET film. Copper electrodes were attached to both ends of the as-prepared film, and the heating characteristics of the film was analyzed while applying DC voltage. The electrical conductivity and the heating temperature of the heating films depended on the size, the structure, the content and the dispersion characteristics of the graphite in the composite. The electrical resistance of the heating film was controlled to adjust the heating temperature of the film. The relationship between the physical/chemical structure and the heating characteristics of the composite film was studied by measuring the heating temperature as functions of film thickness and resistance by using an infrared thermal imaging camera. The lower the film resistance, the higher the heating temperature of the film. The surface temperature was uniform throughout the film.

A frequent co-morbidity of cerebrovascular pathology and Alzheimer's disease pathology has been observed over past decades. Accordingly, much evidence has been reported which indicates that microvascular endothelial dysfunction, due to cerebrovascular risk factors (e.g., atherosclerosis, obesity, diabetes, smoking, hypertension, aging), precedes cognitive decline in Alzheimer's disease and contributes to its pathogenesis. By incorporating appropriate drug(s) into biomimetic (lipid cubic phase) nanocarriers, one obtains a multitasking combination therapeutic which targets certain cell-surface scavenger receptors, mainly class B type I (i.e., SR-BI), and crosses the blood-brain barrier (BBB). Such targeting allows for various Alzheimer's-related cell types to be simultaneously searched out, in vivo, for localized drug treatment. This in vivo targeting advantage may be particularly important for repurposing an FDA-approved drug, especially one which has shown the added ability to restore some cognitive functions in certain animal models of Alzheimer's disease (e.g., the anticancer drug bexarotene); this (candidate repurposing) drug up to now, by itself (i.e, without nanocarrier), displayed poor CNS penetration in human subjects.

Placental growth factor (PlGF or PGF) is a member of the VEGF family, which is known to play a critical role in pathological angiogenesis, inflammation, and endothelial cell barrier function. However, the molecular mechanisms by which PlGF mediates its effects in non-proliferative diabetic retinopathy (DR) remain elusive. In this study, we performed transcriptome-wide profiling of differential gene expression for human retinal endothelial cells (HRECs) treated with PlGF antibody. The effect of antibody treatment on the samples was validated using trans-endothelial electric resistance (TEER), and western blot. A total of 3760 genes (1750 upregulated and 2010 downregulated) were found to be differentially expressed between the control and PlGF antibody treatment group. These differentially expressed genes (DEGs) were used for gene ontology and enrichment analysis to identify gene function, signal pathway, and interaction networks. The gene ontology results revealed that catalytic activity (GO:0003824) of molecular function, cell (GO:0005623) of the cellular component, and cellular process (GO:0009987) were among the most enriched biological processes. Pathways such as TGF-β, VEGF-VEGFR2, p53, apoptosis, pentose phosphate pathway, and ubiquitin-proteasome pathway, were among the most enriched, and TGF-β1 was identified as a primary upstream regulator. These data provide new insights into the underlying molecular mechanisms of PlGF in mediating biological functions, in relation to DR.

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

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.

Cancer is the second biggest cause of death in children. With the development of chemotherapy, there is a substantial increase in overall survival rate over recent 30 years. However, the overall mortality rate in children with cancer still remains 25%, and many survivors experience a decline in overall quality of life and long-term adverse effects caused by treatments. Although cancer cells share common characteristics, pediatric cancers are different from adult cancers in their prevalence, mutation load, and drug response. Therefore, there is an urgent unmet need to develop therapeutic approaches specifically designed for children with cancer. Nanotechnology can potentially overcome the deficiencies of conventional methods of administering chemotherapy and ultimately improve clinical outcomes. The nanoparticle-based drug delivery systems can decrease the toxicity of therapy, provide a sustained or controlled drug release, improve pharmacokinetic properties of loading contents, and achieve a targeted drug delivery with achievable modifications. Further, therapeutic approaches based on combining nanoformulated drugs with novel immunotherapeutic agents are emerging. In this review, we discuss the recently developed nanotechnology-based strategies for treating blood and solid pediatric cancers.

The contribution deals with the joining of various types of materials by technology of thermal drilling. In various branches of industries, also in the automotive industry must be joining operations, service, repairing, substitution or protection workpieces, components with various types of materials. Equally, the important role as joint, is also used material, and a product preparation by assembly and disassembly operations. By utilization of new friction hybrid joining technologies we can shortage the production time, provide automation in operations, increase the quality of joints, spare of economical expenses and also we can protect the environment. In this paper authors have investigated the effect of friction drilling on the tested material, aluminium alloy AlMgSi, which was used for material testing. The created joints were evaluated visually and by microscopy methods. The errors of tested joining were documented and described, too. This contribution was made with cooperation of Technical University of Kosice and with U. S. Steel Kosice, s.r.o.

The sensitivity of macroscopic mechanical and thermal properties of grey cast iron is computationally investigated for a variety of graphite microstructures over a wide temperature range. In order to represent common graphite microstructures according to DIN EN ISO 945-1, a synthetic approach is used to algorithmically generate simulation domains. The developed mechanical and thermal model is applied in a large simulation study. The study includes statistical volume elements of the graphite microstructures classes GG-15 and IA2 to IA5, with 10 v.-%, 11 v.-% and 12 v.-% graphite, respectively, for a temperature range from 20 °C to 750 °C. Homogenized macroscopic quantities such as the Young's moduli, Poisson's ratios, yield strengths and thermal conductivities are predicted for the different microstructure classes by applying simulation and data analysis tools of the research data infrastructure Kadi4Mat.

Sputtered reactive multilayers applied as a heat source in electronic joining processes are an emerging technology. It promises low-stress assembly of components while improving the thermal contact and thus thermal resistance. The use of nanostructures can significantly enhance the adhesion and reliability of joints between different materials. This work presents a phenomenological proof of the hypothesis. Reactive multilayers of nickel and aluminum directly deposited on nanostructured surfaces of silicon wafers and reference samples with flat surface are compared. The investigation of the self-propagating reaction shows a clear influence of the layer thickness, dependent on the multilayer thickness and nanostructure morphology. Rapid thermal annealing results in the formation of Al_1.1Ni_0.9 phase. The necessary annealing temperature is much higher than this applied for nanofoils, sputtered multilayer or particles. The nanostructured interface seems to hinder the full transformation of the present nickel. On the other hand, the surfaces modification improves adhesion of the formed alloy on silicon surfaces and can thus reduce the strength of joints based on reactive aluminum/nickel multilayer . The use of nanostructured surface modifications is thus a promising approach to realized reliable multi-material joints in complex systems.

The aim of this study is to introduce a novel method which can separate sand or gravel dominated bed load transport in rivers with mixed-size bed material. In engineering practice, the Shields-Parker diagram could be used for such purposes, however, the method has certain applicability limits, due to the fact that it is based on uniform bed material and provides information rather on river-scale, instead of reach or local scale. When dealing with large rivers with complex hydrodynamics and morphodynamics the bed load transport modes can also indicate strong variation even locally, which requires a more suitable approach to estimate the locally unique behavior of the sediment transport. Here, we suggest that the decision criteria utilizes the shear Reynolds number (Re*). The method was verified against field and laboratory measurement data, both performed at non-uniform bed material compositions. The comparative assessment of the results show that the shear Reynolds number based method operates more reliably than the Shields-Parker diagram and it is expected to predict the sand or gravel transport domination with a < 5% uncertainty. The introduced results can greatly contribute to the improvement of numerical sediment transport modeling as well as to the field implementation of bed load transport measurements.

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.