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The collapsin response mediator protein (CRMP) family proteins are intracellular mediators of neurotrophic factors regulating neurite structure/spine formation and are essential for dendrite patterning and directional axonal pathfinding during brain developmental processes. selleck chemicals llc Among this family, CRMP5/DPYSL5 plays a significant role in neuronal migration, axonal guidance, dendrite outgrowth, and synapse formation by interacting with microtubules. Here, we report the identification of missense mutations in DPYSL5 in nine individuals with brain malformations, including corpus callosum agenesis and/or posterior fossa abnormalities, associated with variable degrees of intellectual disability. A recurrent de novo p.Glu41Lys variant was found in eight unrelated patients, and a p.Gly47Arg variant was identified in one individual from the first family reported with Ritscher-Schinzel syndrome. Functional analyses of the two missense mutations revealed impaired dendritic outgrowth processes in young developing hippocampal primary neuronal cultures. We further demonstrated that these mutations, both located in the same loop on the surface of DPYSL5 monomers and oligomers, reduced the interaction of DPYSL5 with neuronal cytoskeleton-associated proteins MAP2 and βIII-tubulin. Our findings collectively indicate that the p.Glu41Lys and p.Gly47Arg variants impair DPYSL5 function on dendritic outgrowth regulation by preventing the formation of the ternary complex with MAP2 and βIII-tubulin, ultimately leading to abnormal brain development. This study adds DPYSL5 to the list of genes implicated in brain malformation and in neurodevelopmental disorders.Pulmonary arterial hypertension (PH), a progressive, incurable, and deadly disease, predominantly develops in women. Growing body of evidence suggest that dysregulated estradiol (E2) metabolism influences the development of PH and that some of the biological effects of E2 are mediated by its major non-estrogenic metabolite, 2-metyhoxyestradiol (2ME). The objective of this study was to examine effects of 2ME in chronic hypoxia (CH)-induced PH and alpha-naphthylthiourea (ANTU)-induced acute lung injury and PH. In addition, we investigated the effects of exposure to different levels of CH on development of PH. Chronic exposure to 15% or 10% oxygen produced similar increases in right ventricle peak systolic pressure (RVPSP) and pulmonary vascular remodeling, but oxygen concentration-dependent increase in hematocrit. Notably, right ventricle (RV) hypertrophy correlated with level of hypoxia and hematocrit, rather than with magnitude of RVPSP. The latter suggests that, in addition to increased afterload, hypoxia (via increased hematocrit) significantly contributes to RV hypertrophy in CH model of PH. In CH-PH rats, preventive and curative 2ME treatments reduced both elevated RVPSP and pulmonary vascular remodeling. Curative treatment with 2ME was more effective in reducing hematocrit and right ventricular hypertrophy, as compared to preventive treatment. Single ANTU injection produced lung injury, i.e., increased lungs weight and induced pleural effusion. Treatment with 2ME significantly reduced pleural effusion and, more importantly, eliminated acute mortality induced by ANTU (33% vs 0%, ANTU vs. ANTU+2ME group). Chronic treatment with ANTU induced PH and RV hypertrophy and increased lungs weight. 2-ME significantly attenuated severity of disease (i.e., reduced RVPSP, RV hypertrophy and pulmonary vascular injury). This study demonstrates that 2ME has beneficial effects in chronic hypoxia- and acute lung injury-induced PH and provides preclinical justification for clinical evaluation of 2ME in pulmonary hypertension.Wound healing is a dynamic and physiological process for restoring the normal architecture and functionality of damaged tissue. Platelet-rich plasma (PRP) is an autologous whole blood product that contains a large number of platelets in a small volume of plasma with complete set of coagulation factors, which are in physiological concentrations. PRP has haemostatic, adhesive properties and acts supraphysiologically in the process of wound healing and osteogenesis. Platelets play a very important role in the wound healing process by providing growth factors that enhance the rate and quality of wound healing by many different mechanisms. The aim of this review is to describe the biology of platelets and their role in the wound healing process, the terminology of platelet rich products, PRP preparation, activation and concentration of PRP, as well as the use of PRP in plastic surgery.The outbreak of the COVID-19 pandemic has generated the largest global health crisis of the 21st century, evolving into accelerating socioeconomic disruption. In spite of all rapidly and widely emerging scientific data on epidemiology, diagnosis, prevention and treatment of the COVID-19 disease, severe acute respiratory coronavirus 2 (SARS-CoV-2) is continuing to propagate in lack of definitive and specific therapeutic agents. Current therapeutic strategies are mainly focused on viral inhibition by antiviral drugs and hampering the exuberant immune response of the host by immunomodulatory drugs. In this review, we have studied the reports of the largest clinical trials intended to COVID-19 treatment published during the first year of the pandemics. In general, these results concentrate on seven therapeutic options remdesivir, chloroguine/hydroxychloroquine, lopinavir-ritonavir combination, corticosteroids, tocilizumab, convalescent plasma and monoclonal antibodies. In line with the reviewed data, as of January 2021, most of the evidence support the use of remdesivir in hospitalized patients with moderate and severe forms of the disease and provide reliable data on the substantial beneficial effect of corticosteroids in patients requiring supplemental oxygen. Moreover, preliminary RECOVERY trial results have demonstrated the efficacy of tociluzumab in the treatment of critically ill patients. The reports presenting the outcomes of the other immune-based therapies under investigation are enthusiastically awaited.Brachial plexus injuries are still challenging for every surgeon taking part in treating patients with BPI. Injuries of the brachial plexus can be divided into injuries of the upper trunk, extended upper trunk, injuries of the lower trunk and swinging hand where all of the roots are involved in this type of the injury. Brachial plexus can be divided in five anatomical sections from its roots to its terminal branches roots, trunks, division, cords and terminal branches. Brachial plexus ends up as five terminal branches, responsible for upper limb innervation, musculocutaneous, median nerve, axillary nerve, radial and ulnar nerve. According to the findings from the preoperative investigation combined with clinically found functional deficit, the type of BPI will be confirmed and that is going to determine which surgical procedure, from variety of them (neurolysis, nerve graft, neurotization, arthrodesis, tendon transfer, free muscle transfer, bionic reconstruction) is appropriate for treating the patient.
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