20 research outputs found
Children with developmental coordination disorders: a review of approaches to assessment and intervention
Developmental Coordination Disorder (DCD) is a neurodevelopmental disorder characterized by deficits in motor skills, with gross and fine motor dysfunction being the main symptom. This condition greatly impairs children’s daily life, learning, and social interaction. Symptoms typically appear during preschool or school age, and if left untreated, they can persist into adulthood. Thus, early assessment and intervention are crucial to improve the prognosis. This study aims to review the existing literature on DCD, providing a comprehensive overview of the assessment for children with DCD in terms of body functions and structures, activities and participation, and environmental factors within the framework of the International Classification of Functioning, Disability, and Health - Children and Youth (ICF-CY). Additionally, specific rehabilitation interventions will be described, offering valuable insights for the clinical assessment and intervention of children with DCD
Tauroursodeoxycholic acid: a bile acid that may be used for the prevention and treatment of Alzheimer’s disease
Alzheimer’s disease (AD) is a prevalent neurodegenerative disease that has become one of the main factors affecting human health. It has serious impacts on individuals, families, and society. With the development of population aging, the incidence of AD will further increase worldwide. Emerging evidence suggests that many physiological metabolic processes, such as lipid metabolism, are implicated in the pathogenesis of AD. Bile acids, as the main undertakers of lipid metabolism, play an important role in the occurrence and development of Alzheimer’s disease. Tauroursodeoxycholic acid, an endogenous bile acid, has been proven to possess therapeutic effects in different neurodegenerative diseases, including Alzheimer’s disease. This review tries to find the relationship between bile acid metabolism and AD, as well as explore the therapeutic potential of bile acid taurocursodeoxycholic acid for this disease. The potential mechanisms of taurocursodeoxycholic acid may include reducing the deposition of Amyloid-β protein, regulating apoptotic pathways, preventing tau hyperphosphorylation and aggregation, protecting neuronal synapses, exhibiting anti-inflammatory properties, and improving metabolic disorders. The objective of this study is to shed light on the use of tauroursodeoxycholic acid preparations in the prevention and treatment of AD, with the aim of identifying effective treatment targets and clarifying various treatment mechanisms involved in this disease
AltitudeOmics: Red Blood Cell metabolic adaptation to high altitude hypoxia
Red blood cells (RBCs) are key players in systemic oxygen transport. RBCs respond to in vitro hypoxia through the so-called oxygen-dependent metabolic regulation, which involves the competitive binding of deoxyhemoglobin and glycolytic enzymes to the N-terminal cytosolic domain of band 3. This mechanism promotes the accumulation of 2,3-DPG, stabilizing the deoxygenated state of hemoglobin, and cytosol acidification, triggering oxygen off-loading through the Bohr effect. Despite in vitro studies, in vivo adaptations to hypoxia have not yet been completely elucidated. Within the framework of the AltitudeOmics study, erythrocytes were collected from 21 healthy volunteers at sea level, after exposure to high altitude (5260m) for 1, 7 and 16days, and following reascent after 7days at 1525m. UHPLC-MS metabolomics results were correlated to physiological and athletic performance parameters. Immediate metabolic adaptations were noted as early as a few hours from ascending to >5000m, and maintained for 16 days at high altitude. Consistent with the mechanisms elucidated in vitro, hypoxia promoted glycolysis and deregulated the pentose phosphate pathway, as well purine catabolism, glutathione homeostasis, arginine/nitric oxide and sulphur/H2S metabolism. Metabolic adaptations were preserved one week after descent, consistently with improved physical performances in comparison to the first ascendance, suggesting a mechanism of metabolic memory
Hypoxia modulates the purine salvage pathway and decreases red blood cell and supernatant levels of hypoxanthine during refrigerated storage
Hypoxanthine catabolism in vivo is potentially dangerous as it fuels production of urate and, most importantly, hydrogen peroxide. However, it is unclear whether accumulation of intracellular and supernatant hypoxanthine in stored red blood cell units is clinically relevant for transfused recipients. Leukoreduced red blood cells from glucose-6-phosphate dehydrogenase-normal or -deficient human volunteers were stored in AS-3 under normoxic, hyperoxic, or hypoxic conditions (with oxygen saturation ranging from 95%). Red blood cells from healthy human volunteers were also collected at sea level or after 1–7 days at high altitude (>5000 m). Finally, C57BL/6J mouse red blood cells were incubated in vitro with 13C1-aspartate or 13C5-adenosine under normoxic or hypoxic conditions, with or without deoxycoformycin, a purine deaminase inhibitor. Metabolomics analyses were performed on human and mouse red blood cells stored for up to 42 or 14 days, respectively, and correlated with 24 h post-transfusion red blood cell recovery. Hypoxanthine increased in stored red blood cell units as a function of oxygen levels. Stored red blood cells from human glucose-6-phosphate dehydrogenase-deficient donors had higher levels of deaminated purines. Hypoxia in vitro and in vivo decreased purine oxidation and enhanced purine salvage reactions in human and mouse red blood cells, which was partly explained by decreased adenosine monophosphate deaminase activity. In addition, hypoxanthine levels negatively correlated with post-transfusion red blood cell recovery in mice and – preliminarily albeit significantly - in humans. In conclusion, hypoxanthine is an in vitro metabolic marker of the red blood cell storage lesion that negatively correlates with post-transfusion recovery in vivo. Storage-dependent hypoxanthine accumulation is ameliorated by hypoxia-induced decreases in purine deamination reaction rates
INHIBITION OF MAP KINASE-INTERACTING KINASE (MNK) PREFERENTIALLY AFFECTS TRANSLATION OF mRNAs CONTAINING BOTH A 5’-TERMINAL CAP AND HAIRPIN
Background: Modulation of MNK 1 and 2
affects translation of mRNAs involved in the
cell cycle, cancer progression, and cell survival.
Result: Inhibition of MNK activity in rabbit
reticulocyte lysate affects translation of only
mRNAs containing both 5’-terminal cap and
hairpin.
Conclusion: MNK regulates translation via
altering interactions among the eIF4E and
eIF4G.
Significance: MNK affects the eIF4F assembly