American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19

Background: Coronavirus disease 2019 (COVID-19)-related critical illness and acute illness are associated with a risk of venous thromboembolism (VTE).Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis for patients with COVID-19-related critical illness and acute illness who do not have confirmed or suspected VTE.Methods: ASH formed a multidisciplinary guideline panel and applied strict management strategies to minimize potential bias from conflicts of interest. The panel included 3 patient representatives. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic evidence reviews (up to 19 August 2020). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment.Results: The panel agreed on 2 recommendations. The panel issued conditional recommendations in favor of prophylactic-intensity anticoagulation over intermediate-intensity or therapeutic-intensity anticoagulation for patients with COVID-19-related critical illness or acute illness who do not have confirmed or suspected VTE.Conclusions: These recommendations were based on very low certainty in the evidence, underscoring the need for high-quality, randomized controlled trials comparing different intensities of anticoagulation. They will be updated using a living recommendation approach as new evidence becomes available.Thrombosis and Hemostasi

American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: May 2021 update on the use of intermediate-intensity anticoagulation in critically ill patients

Background: COVID-19-related critical illness is associated with an increased risk of venous thromboembolism (VTE). Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE.Methods: ASH formed a multidisciplinary guideline panel that included 3 patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process by performing systematic evidence reviews (up to 5 March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update on guidelines published in February 2021.Results: The panel agreed on 1 additional recommendation. The panel issued a conditional recommendation in favor of prophylactic-intensity over intermediate-intensity anticoagulation in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE.Conclusions: This recommendation was based on low certainty in the evidence, which underscores the need for additional high-quality, randomized, controlled trials comparing different intensities of anticoagulation in critically ill patients. Other key research priorities include better evidence regarding predictors of thrombosis and bleeding risk in critically ill patients with COVID-19 and the impact of nonanticoagulant therapies (eg, antiviral agents, corticosteroids) on thrombotic risk.Thrombosis and Hemostasi

Differential distribution of MAP1a and aldolase c in adult mouse cerebellum.

MAP1a is a microtubule-associated protein with an apparent molecular weight of 360 kDa that is found in the axonal and dendritic processes of neurons. Two monoclonal anti-MAP1a antibodies anti-A and anti-BW6, revealed different epitope distributions in the adult mouse cerebellum. Anti-A stained Purkinje and granule cells uniformly throughout the cerebellum. In contrast, anti-BW6 selectively stained the dendriites of a subset of Purkinje cells, revealing parasagittal bands of immunoreactivity in the molecular layer. The compartmentation of the BW6 epitope was compared to the Purkine cells as revealed by immunostaining with anti-zebrin II, a well known antigen expressed selectively by bands of Purkinje cells. The anti-BW6 staining pattern was complementary to the zebrin II bands, the zebrin II- Purkinjke cells having BW6+ dendrites. These results demonstrate that MAP1a is present in two forms in the mouse cerebellum, one of which is segregated into parasagittal bands. This may indicate a unique MAP1a isoform or may reflect differences in the metabolic states of Purkinje cell classes, and regional differences in their functions

Optimisation and biological activities of bioceramic robocast scaffolds provided with an oxygen-releasing coating for bone tissue engineering applications

Hypoxia is one of the major challenges after scaffold implantation which can lead to cell necrosis and bacterial infection. Using of supplemental oxygen can increase the cell proliferation, encourage the cell differentiation and prevent the infections. Developing an engineered scaffold with a sustained oxygen release is an outstanding way for addressing the challenges of oxygen deficiency. In this study, the bioceramic scaffolds were fabricated from biphasic calcium phosphate (BCP) powder with the composition of 60 hydroxyapatite (HA) and 40 beta-tricalcium phosphate (β-TCP). The Robocasting technique was utilised for producing a porous structure comprising interpenetrated ceramic rods in a 3-dimensional tetragonal mesh. The scaffold was modelled by the finite element method (FEM) for computing the stress fields and predicting their mechanical performance. Calcium peroxide (CPO), as an oxygen-producing and antimicrobial biomaterial, was mixed with a polycaprolactone (PCL) solution and was coated on the scaffolds by the dip-coating method. The coating layer possessed three different percentages of CPO (1, 3 and 5 wt). The oxygen-releasing profile proved that this design of coating-scaffold could be effective as a system of oxygen delivery. According to the antibacterial investigations, releasing of CPO from the scaffolds could inhibit the growth of E. coli and S. aureus. SBF tests confirmed that the coated scaffolds because of CPO particles on their surface presented superior apatite precipitation in comparison with the uncoated one. The differentiated osteoblastic function was monitored by measuring the alkaline phosphatase (ALP) activity. The coated BCP scaffolds with 3 and 5 CPO exhibited higher ALP activity compared to the other samples. The results demonstrated that the proposed bioceramic-based scaffolds containing oxygen-generating coating could be optimised to supply an antibacterial performance, ideal mechanical properties, improved ALP activity and higher apatite formation ability. Therefore, these scaffolds can be a promising candidate for applying in bone tissue engineering. © 2018 Elsevier Ltd and Techna Group S.r.l

3D�printed biphasic calcium phosphate scaffolds coated with an oxygen generating system for enhancing engineered tissue survival

Tissue engineering scaffolds with oxygen generating elements have shown to be able to increase the level of oxygen and cell survivability in specific conditions. In this study, biphasic calcium phosphate (BCP) scaffolds with the composition of 60 hydroxyapatite (HA) and 40 beta-tricalcium phosphate (β-TCP), which have shown a great potential for bone tissue engineering applications, were fabricated by a direct-write assembly (robocasting) technique. Then, the three-dimensional (3D)-printed scaffolds were coated with different ratios of an oxygen releasing agent, calcium peroxide (CPO), which encapsulated within a polycaprolactone (PCL) matrix through dip-coating, and used for in situ production of oxygen in the implanted sites. The structure, composition and morphology of the prepared scaffolds were characterized by different techniques. The oxygen release kinetics and biological investigations of the scaffolds were also studied in vitro. The results showed that oxygen release behaviour was sustained and dependant on the concentration of CPO encapsulated in the PCL coating matrix. It was also demonstrated that the coated scaffolds, having 3 CPO in the coating system, could provide a great potential for promoting bone ingrowth with improving osteoblast cells viability and proliferation under hypoxic conditions. The findings indicated that the prepared scaffolds could play a significant role in engineering of large bone tissue implants with limitations in oxygen diffusion. © 201

Microtubule-associated protein 1a is involved in the early development of the rat spinal cord.

The expression of microtubule-associated protein 1a (MAP1a) in the developing rat spinal cord was studied using the monoclonal antibody BW6. Immunoblots of microtubule preparations revealed the presence of MAP1a in spinal cord tissue of rats aged embryonal day 16 and postnatal day 0. The spinal cord matrix layer, between embryonal days 12-17, displayed a pattern of MAP1a-positive processes, horizontally oriented in between the membrane limitans interna and externa. The mantle layer stained intensely for MAP1a between embryonal day 12 and postnatal day 2. MAP1a was found in neuronal cell bodies, axons and dendrites, located mainly in the ventral and intermediate mantle layer. In the marginal layer, MAP1a-positive axons could be observed between embryonal days 14-18. During further development, the intensity of the MAP1a staining in the spinal columns gradually decreased. These expression patterns indicate an involvement of MAP1a in the proliferation and differentiation of neuroblasts, and the maturation of the long spinal fiber systems, i.e. early events in spinal cord developmen

Immunocytochemical localisation of microtubule-associated proteins 1b and 2 in the developing rat spinal cord.

The straightforward anatomical organisation of the developing and mature rat spinal cord was used to determine and interpret the time of appearance and expression patterns of microtubule-associated proteins (MAP) 1b and 2. Immunoblots revealed the presence of MAP1b and 2 in the early embryonic rat spinal cord and confirmed the specificity of the used anti-MAP mouse monoclonal antibodies. The immunocytochemical data demonstrated a rostral-to-caudal and ventral-to-dorsal gradient in the expression of MAP1b/2 within the developing spinal cord. In the matrix layer, MAP1b was found in a distinct radial pattern distributed between the membrana limitans interna and externa between embryonal day (E)12 and E15. Immunostaining for vimentin revealed that this MAP1b pattern was morphologically and topographically different from the radial glial pattern which was present in the matrix layer between E13 and E19. The ventral-to-dorsal developmental gradient of the MAP1b staining in the spinal cord matrix layer indicates a close involvement of MAP1b either in the organisation of the microtubules in the cytoplasmatic extensions of the proliferating neuroblasts or neuroblast mitosis. MAP2 could not be detected in the developing matrix layer. In the mantle and marginal layer, MAP1b was abundantly present between E12 and postnatal day (P)0. After birth, the staining intensity for MAP1b gradually decreased in both layers towards a faint appearance at maturity. The distribution patterns suggest an involvement of MAP1b in the maturation of the motor neurons, the contralaterally and ipsilaterally projecting axons and the ascending and descending long axons of the rat spinal cord. MAP2 was present in the spinal cord grey matter between E12 and maturity, which reflects a role for MAP2 in the development as well as in the maintenance of microtubules. The present description of the expression patterns of MAP1b and 2 in the developing spinal cord suggests important roles of the two proteins in various morphogenetic events. The findings may serve as the basis for future studies on the function of MAP1b and 2 in the development of the central nervous system

Additive Manufacturing of Biomaterials � The Evolution of Rapid Prototyping

Biomaterials rapid prototyping (RP), recently known as additive manufacturing (AM), has appeared as a revolutionary technology, promising to transform research into medical therapeutics. RP is a layer by layer manufacturing process which directly translates computer data such as Computer Aided Design (CAD), Computer Tomography (CT), and Magnetic Resonance Imaging (MRI) into three-dimensional (3D) objects. RP technologies play a significant role in biomedical industry such as anatomical models for surgery training/planning, rehabilitation, dentistry, customized implants, drug delivery devices, tissue engineering, and organ printing. The integration of biomaterials and rapid prototyping technologies is an exciting route in developing biomaterial implants for the past decade. This review describes and classifies the RP systems into three categories of liquid-based, solid-based, and powder-based according to the initial form of their feed materials. Then, discusses possible benefits, drawbacks, and applications of each process in the field of biomaterials science and engineering. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei