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This systematic review and meta-analysis included randomized controlled trials or observational studies that compare digital health interventions (DHIs) for telemedicine/telehealth versus usual care for managing blood pressure (BP) in adults. We searched PubMed, Cochrane CENTRAL, and IchuShi-Web, and used a random-effects meta-analysis of the weighted mean difference (MD) between the comparison groups to pool data from the included studies. The outcome included the pooled MD of office BP from baseline to each follow-up period. This meta-analysis considered 117 studies with 68677 participants as eligible. The 3-month intervention period reduced office systolic BP (SBP) compared with usual care in 38 studies (MD: -3.21 mmHg [95% confidence interval: -4.51 to -1.90]), with evidence of heterogeneity. Office SBP across intervention periods demonstrated comparable effects (3-, 6- [54 studies], 12- [43 studies], and >12-month periods [9 studies]). The benefits for office diastolic BP were similar to those for office SBP. Additionally, the interventions significantly reduced the office SBP compared with the control, regardless of the mode of intervention delivery (smartphone apps [38 studies], text messages [35 studies], and websites [34 studies]) or type of facility (medical [74 studies] vs. non-medical [33 studies]). The interventions were more effective in 41 hypertension cohorts compared with 66 non-hypertension cohorts (-4.81 mmHg [-6.33, -3.29] vs. -2.17 mmHg [-3.15, -1.19], P = 0.006 for heterogeneity). In conclusion, DHIs for telemedicine/telehealth improved BP management compared with usual care. The effectiveness with heterogeneity should be considered, as prudent for implementing evidence-based medicine. This meta-analysis considered 117 studies with 68677 participants eligible. The DHIs for telemedicine/telehealth reduced office BP compared with usual care, regardless of intervention duration, intervention delivery mode, facility type, and cohort type. Additionally, the DHIs reduced the risk of uncontrolled BP compared with usual care, regardless of intervention duration, intervention delivery mode, and facility type. BP blood pressure, DHI digital health intervention, MD mean difference, RR risk ratio, SBP systolic blood pressure.
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The Human Glycome Atlas (HGA) Project was launched in April 2023, spearheaded by three Japanese institutes: the Tokai National Higher Education and Research System, the National Institutes of Natural Sciences, and Soka University. This was the first time that a field in the life sciences was adopted by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) for a Large-scale Academic Frontiers Promotion Project. This project aims to construct a knowledgebase of human glycans and glycoproteins as a standard for the human glycome. A high-throughput pipeline for comprehensively analyzing 20,000 blood samples in its first five years is planned, at which time an access-controlled version of a human glycomics knowledgebase, called TOHSA, will be released. By the end of the final tenth year, TOHSA will provide a central resource linking human glycan data with other omics data including disease-related information.
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Radial neuronal migration is a key neurodevelopmental event for proper cortical laminar organization. The multipolar-to-bipolar transition, a critical step in establishing neuronal polarity during radial migration, occurs in the subplate/intermediate zone (SP/IZ), a distinct region of the embryonic cerebral cortex. It has been known that the extracellular matrix (ECM) molecules are enriched in the SP/IZ. However, the molecular constitution and functions of the ECM formed in this region remain poorly understood. Here, we identified neurocan (NCAN) as a major chondroitin sulfate proteoglycan in the mouse SP/IZ. NCAN binds to both radial glial-cell-derived tenascin-C (TNC) and hyaluronan (HA), a large linear polysaccharide, forming a ternary complex of NCAN, TNC, and HA in the SP/IZ. Developing cortical neurons make contact with the ternary complex during migration. The enzymatic or genetic disruption of the ternary complex impairs radial migration by suppressing the multipolar-to-bipolar transition. Furthermore, both TNC and NCAN promoted the morphological maturation of cortical neurons in vitro. The present results provide evidence for the cooperative role of neuron- and radial glial-cell-derived ECM molecules in cortical development.
Assuntos
Matriz Extracelular , Neurônios , Animais , Camundongos , Neurônios/fisiologia , Matriz Extracelular/metabolismo , Córtex Cerebral/metabolismo , Movimento Celular/fisiologia , Proteoglicanas de Sulfatos de Condroitina/metabolismoRESUMO
We recently established a method for the isolation of serum-free oligosaccharides, and characterized various features of their structures. However, the precise mechanism for how these glycans are formed still remains unclarified. To further investigate the mechanism responsible for these serum glycans, here, we utilized rat primary hepatocytes to examine whether they are able to secrete free glycans. Our findings indicated that a diverse array of free oligosaccharides such as sialyl/neutral free N-glycans (FNGs), as well as sialyl lactose/LacNAc-type glycans, were secreted into the culture medium by primary hepatocytes. The structural features of these free glycans in the medium were similar to those isolated from the sera of the same rat. Further evidence suggested that an oligosaccharyltransferase is involved in the release of the serum-free N-glycans. Our results indicate that the liver is indeed secreting various types of free glycans directly into the serum.
Assuntos
Hepatócitos , Oligossacarídeos , Animais , Ratos , Hepatócitos/metabolismo , Oligossacarídeos/sangue , Oligossacarídeos/química , Oligossacarídeos/metabolismo , Células Hep G2 , Humanos , Masculino , Ratos WistarRESUMO
The polysialyltransferases ST8SIA2 and ST8SIA4 and their product, polysialic acid (polySia), are known to be related to cancers and mental disorders. ST8SIA2 and ST8SIA4 have conserved amino acid (AA) sequence motifs essential for the synthesis of the polySia structures on the neural cell adhesion molecule. To search for a new motif in the polysialyltransferases, we adopted the in silico Individual Meta Random Forest program that can predict disease-related AA substitutions. The Individual Meta Random Forest program predicted a new eight-amino-acids sequence motif consisting of highly pathogenic AA residues, thus designated as the pathogenic (P) motif. A series of alanine point mutation experiments in the pathogenic motif (P motif) showed that most P motif mutants lost the polysialylation activity without changing the proper enzyme expression levels or localization in the Golgi. In addition, we evaluated the enzyme stability of the P motif mutants using newly established calculations of mutation energy, demonstrating that the subtle change of the conformational energy regulates the activity. In the AlphaFold2 model, we found that the P motif was a buried ß-strand underneath the known surface motifs unique to ST8SIA2 and ST8SIA4. Taken together, the P motif is a novel buried ß-strand that regulates the full activity of polysialyltransferases from the inside of the molecule.