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OBJECTIVES: Extracellular matrix components play a significant role in maintaining tissue integrity and pathological processes of the temporomandibular joint (TMJ). This study aimed to evaluate the influence of a soft diet on the mRNA expression of proteoglycans and glycosaminoglycans (GAGs) linked to proteoglycan core proteins in rat TMJ discs. METHODS: Thirty 4-week-old male Wistar rats were assigned to one of two groups: a control group fed a regular pellet diet and a soft diet group fed a powdered diet for 4 weeks. The mRNA expression levels of 12 proteoglycans in TMJ discs were evaluated using real-time polymerase chain reaction (PCR). In addition, histomorphometric and biochemical analyses were performed to evaluate the thickness and deoxyribonucleic acid (DNA), GAG, and water content of the TMJ discs. RESULTS: The TMJ disc thickness in the anterior, intermediate, and posterior bands decreased significantly in the soft diet group. The GAG content decreased significantly in the soft-diet group, whereas no significant differences in DNA content or water content ratio were observed between the groups. Real-time PCR indicated that the expression levels of aggrecan, versican, biglycan, decorin, fibromodulin, lumican, and chondroadherin decreased in the soft diet group. The expression levels of all versican isoforms decreased in the soft diet group. CONCLUSIONS: These results indicate that the biomechanical environment of the TMJ caused by a soft diet is closely related to the expression of proteoglycans in TMJ discs, which may eventually increase the fragility of the TMJ discs.
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Proteoglicanos , Ratas Wistar , Disco de la Articulación Temporomandibular , Animales , Proteoglicanos/metabolismo , Proteoglicanos/genética , Ratas , Masculino , Disco de la Articulación Temporomandibular/metabolismo , Disco de la Articulación Temporomandibular/patología , Reacción en Cadena en Tiempo Real de la Polimerasa , Dieta/efectos adversos , Glicosaminoglicanos/metabolismo , ARN Mensajero/metabolismo , ARN Mensajero/genéticaRESUMEN
Background: We investigated treatment outcomes and post-treatment stability in 10 patients with an anterior open bite and nonsurgical orthodontics. Methods: The patients underwent maxillary molar intrusion using temporary anchorage devices (TADs) to deepen the overbite due to mandibular autorotation. Lateral cephalograms and dental cast models were obtained before treatment (T0), immediately after it (T1), and >1 year after it (T2). Skeletal and dental cephalometric changes and three-dimensional movements of the maxillary dentitions were evaluated. Results: At T0, cephalometric analysis indicated that patients had skeletal class I with tendencies for a class II jaw relationship and a skeletal open bite. During active treatment (T0 to T1), the maxillary first molar intruded by 1.6 mm, the mandibular first molar extruded by 0.3 mm, the Frankfort-mandibular plane angle decreased by 1.1°, and the overbite increased by 4.1 mm. Statistically significant changes were observed in the amount of vertical movement of the maxillary first molar, Frankfort-mandibular plane angle, and overbite. Three-dimensional (3D) dental cast analysis revealed that the maxillary first and second molars intruded, whereas the anterior teeth extruded, with the second premolar as an infection point. In addition, the maxillary molar was tipped distally by 2.9° and rotated distally by 0.91°. Statistically significant changes were observed in the amount of vertical movement of the central incisor, lateral incisor, canine and first molar, and molar angulation. From T1 to T2, no significant changes in cephalometric measurements or the 3D position of the maxillary dentition were observed. The maxillary and mandibular dentitions did not significantly change during post-treatment follow-up. Conclusions: Maxillary molar intrusion using mini-screws is an effective treatment for open bite correction, with the achieved occlusion demonstrating 3D stability at least 1 year after treatment.
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BACKGROUND: Sleep consolidation into nighttime is considered the primary goal of sleep development in early infants. However, factors contributing to sleep consolidation into nighttime remain unclear. AIM: To clarify the influences of the light environment and nighttime co-sleeping on sleep consolidation into nighttime in early infants. STUDY DESIGN: Cross-sectional study. SUBJECTS AND METHODS: Sleep-wake time and light stimulation were measured in infants for 4 consecutive days using actigraphy. The infants' mothers were asked to complete a sleep events diary and a questionnaire about childcare, including "co-sleeping", defined as when the infant and mother slept on the same surface throughout the night. OUTCOME MEASURES: The data were analyzed with a focus on daytime and nighttime sleep parameters. RESULTS: Daytime light stimulation reduced daytime "active sleep", tended to reduce daytime sleep, and increased daytime waking. Nighttime light stimulation reduced nighttime "quiet sleep" and nighttime sleep and increased nighttime waking. Co-sleeping reduced nighttime waking, and, as a result, nighttime sleep time and sleep efficiency increased. Co-sleeping reduced daytime sleep and tended to increase daytime waking. Consequently, co-sleeping tended to increase the ratio of nighttime sleep to daytime sleep. CONCLUSIONS: The present findings suggest that an appropriate light environment promotes daytime waking and nighttime sleep in early infants, but it does not contribute to sleep consolidation into nighttime by itself. On the other hand, co-sleeping may promote sleep consolidation into nighttime. Therefore, further methods for safe co-sleeping need to be established while avoiding risk factors for sudden unexpected death in infancy/sudden infant death syndrome.
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Sueño , Muerte Súbita del Lactante , Humanos , Lactante , Femenino , Proyectos Piloto , Estudios Transversales , Sueño/fisiología , MadresRESUMEN
A 65-year-old man presented with apparent bronchopneumonia. After treatment with antibiotics, he showed eosinophilia. Computed tomography (CT) imaging revealed bilateral consolidation, ground-glass opacities with nodular consolidations, and pleural effusion. Lung biopsy showed organising pneumonia with lymphoplasmacytic infiltration in the alveolar septa and in the thickened pleura and interlobular septa. All pulmonary abnormalities spontaneously went into remission within 12 months. At 73 years old, a follow-up CT scan revealed small nodules in both lungs and the review of the head CT scan showed thickening of the pituitary stalk in studying prolonged headache. Two years later, he visited the hospital complaining of severe oedema on the lower extremities with high serum immunoglobulin (Ig)G4 186 mg/dl. A whole-body CT scan showed retroperitoneal mass surrounding aortic bifurcation and compressing inferior vena cava, pituitary stalk thickening and gland swelling, and enlarged pulmonary nodules. Anterior pituitary stimulation tests showed central hypothyroidism, central hypogonadism, and adult growth hormone deficiency with partial primary hypoadrenocorticism. Retroperitoneal mass biopsy showed storiform fibrosis and obliterative phlebitis with marked lymphoplasmacytic infiltration with moderate IgG4-positivity. Immunostaining of the former lung specimen revealed dense interstitial infiltration of IgG4-positive cells. These findings indicated metachronous development of IgG4-related disease in lung, hypophysis, and retroperitoneum, according to the recent comprehensive diagnostic criteria of IgG4-related disease. Glucocorticoid therapy ameliorated oedema, on the other hand, unmasked partial diabetes insipidus at the initial dose of the treatment. Hypothyroidism and retroperitoneal mass regressed at 6 months of the treatment. This case warns us that long-term follow-up from prodromal to remission is necessary for the treatment of IgG4-related disease.
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Hipofisitis , Enfermedad Relacionada con Inmunoglobulina G4 , Enfermedades Pulmonares , Fibrosis Retroperitoneal , Masculino , Adulto , Humanos , Anciano , Niño , Enfermedad Relacionada con Inmunoglobulina G4/complicaciones , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Enfermedad Relacionada con Inmunoglobulina G4/tratamiento farmacológico , Fibrosis Retroperitoneal/complicaciones , Fibrosis Retroperitoneal/diagnóstico , Remisión Espontánea , Hipofisitis/tratamiento farmacológico , Inmunoglobulina G/uso terapéutico , EdemaRESUMEN
Spinal muscular atrophy (SMA) is a congenital neuromuscular disease caused by the mutation or deletion of the survival motor neuron 1 (SMN1) gene. Although the primary cause of progressive muscle atrophy in SMA has classically been considered the degeneration of motor neurons, recent studies have indicated a skeletal muscle-specific pathological phenotype such as impaired mitochondrial function and enhanced cell death. Here, we found that the down-regulation of SMN causes mitochondrial dysfunction and subsequent cell death in in vitro models of skeletal myogenesis with both a murine C2C12 cell line and human induced pluripotent stem cells. During myogenesis, SMN binds to the upstream genomic regions of MYOD1 and microRNA (miR)-1 and miR-206. Accordingly, the loss of SMN down-regulates these miRs, whereas supplementation of the miRs recovers the mitochondrial function, cell survival, and myotube formation of SMN-deficient C2C12, indicating the SMN-miR axis is essential for myogenic metabolic maturation. In addition, the introduction of the miRs into ex vivo muscle stem cells derived from Δ7-SMA mice caused myotube formation and muscle contraction. In conclusion, our data revealed novel transcriptional roles of SMN during myogenesis, providing an alternative muscle-oriented therapeutic strategy for SMA patients.
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Células Madre Pluripotentes Inducidas , MicroARNs , Atrofia Muscular Espinal , Proteína 1 para la Supervivencia de la Neurona Motora , Animales , Humanos , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Mitocondrias/metabolismo , Desarrollo de Músculos/genética , Músculo Esquelético/metabolismo , Atrofia Muscular Espinal/genética , Proteína 1 para la Supervivencia de la Neurona Motora/genética , Proteína 1 para la Supervivencia de la Neurona Motora/metabolismoRESUMEN
Diamond Blackfan anemia (DBA) is a chronic congenital form of erythrocytic hypoplasia in which erythroid precursor cell levels are low. DBA reflects ribosomal dysfunction and is accompanied by hematopoietic cell apoptosis, anemia, and various somatic symptoms. We report the characteristic symptoms of the craniofacial region and the orthodontic treatments of two DBA cases. Case 1 was a 12-year-old female. The typical physical and facial characteristics of DBA were lacking. On initial examination, she exhibited a skeletal Class II jaw and end to end molar relationships and a large overjet. An edgewise appliance was placed after extraction of the first maxillary premolars. After 3 years and 11 months, an appropriate overjet and overbite, rigid intercuspation, and an acceptable profile were evident without any clinical adverse effects. Case 2 was a 13-year-old female. She exhibited a skeletal Class I jaw relationship, a spaced dental arch, the maxillofacial dysplasia characteristic of Binder syndrome, hypoplasia of the right mandibular condyle, and labial protrusions of the maxillary and mandibular incisors. We placed an edgewise appliance and after 1 year and 7 months, the occlusion was optimal in the absence of any adverse effects. Our two DBA cases exhibited a broad spectrum of physical and dentofacial symptoms. Patients with DBA are often prescribed combined steroid/bisphosphonate therapies. Both agents are likely to affect alveolar bone remodeling after tooth extraction and orthodontic tooth movement. Careful consideration of medication with reference to various dentofacial characteristics is necessary.
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Anemia de Diamond-Blackfan , Adolescente , Niño , Humanos , Anemia de Diamond-Blackfan/terapia , Ortodoncia CorrectivaRESUMEN
A number of studies have been made on the sleep characteristics of children born preterm in an attempt to develop methods to address the sleep problems commonly observed among such children. However, the reported sleep characteristics from these studies vary depending on the observation methods used, i.e., actigraphy, polysomnography and questionnaire. In the current study, to obtain reliable data on the sleep characteristics of preterm-born children, we investigated the difference in sleep properties between 97 preterm and 97 term toddlers of approximately 1.5 years of age using actigraphy. Actigraphy units were attached to the toddlers' waists with an adjustable elastic belt for 7 consecutive days, and a child sleep diary was completed by their parents. In the study, we found that preterm toddlers had more nocturnal awakenings and more daytime activity, suggesting that preterm-born children may have a different process of sleep development in their early development.
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Calidad del Sueño , Sueño , Preescolar , Humanos , Recién Nacido , Actigrafía , Polisomnografía , Recien Nacido PrematuroRESUMEN
BACKGROUND: Although several school-based cognitive behavioural intervention programmes have been developed in Japan to prevent and improve children's anxiety disorders, the substantial time required for their completion remains a problem. METHODS: A brief version of the cognitive behavioural programme called 'Journey of the Brave', developed for Japanese children was conducted among 90 children aged 10â11 years using 20-min short classroom activities, and its effectiveness was examined. The children were divided into two groups: the intervention (n = 31) and control groups (n = 59). The control group did not attend any programme sessions and followed regular school curriculum. We conducted 14 weekly programme sessions and assessed children at pre-intervention, post-intervention, and 2-month follow-up (6 months after the beginning). The primary and secondary outcome measures were the Spence Children's Anxiety Scale (SCAS) to assess children's anxiety symptoms and the Strengths and Difficulties Questionnaire (SDQ) to measure behaviour problems, respectively. RESULTS: A statistically significant reduction in the SCAS score in the intervention group was found at 2-month follow-up compared with the control group. A significant reduction was also observed in the SDQ score. CONCLUSIONS: Our findings suggested that the 'Journey of the Brave' programme, which requires only 5 h of short classroom activities, demonstrates promising results compared with previous programmes. A larger randomised control trial would be desirable. TRIAL REGISTRATION: UMIN, UMIN000009021, Registered 10 March 2012.
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Ansiedad , Instituciones Académicas , Niño , Humanos , Japón , Ansiedad/terapia , Trastornos de Ansiedad/terapia , CogniciónRESUMEN
The Streptococcus mitis group constitutes a part of the oral flora in humans and has been reported to cause infective endocarditis, brain abscesses, sepsis, pneumonia, and peritonitis. However, the S. mitis group rarely causes meningitis in children. We experienced a case of bacterial meningitis due to the S. mitis group in a 14-year-old girl with Gorham-Stout disease undergoing treatment with sirolimus for skull base osteolysis and cerebrospinal fluid (CSF) leak. Antibiotic treatment was initiated with linezolid and levofloxacin due to allergies against ß-lactam antibiotics. On the third treatment day, antibiotics were switched to penicillin G according to CSF culture results, which were positive for penicillin-susceptible S. mitis group. Antibiotic therapy was successfully completed after 14 days without any neurological sequelae. There have apparently been no reports of S. mitis meningitis in pediatric patients with skull base osteolysis and CSF leak as in our case. Our findings suggest that clinicians should be aware of the possibility of S. mitis meningitis for patients with skull base osteolysis and/or CSF leakage.
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PURPOSE: Decline in physical function in the early stage after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a major challenge. Exercise tolerance tests, such as the 6-min walk test, are useful markers for predicting exercise tolerance and various other traits, including cardiometabolic risk and non-relapse mortality. This retrospective cohort study aimed to investigate and identify predictors of recovery of exercise tolerance in the early stage after allo-HSCT. METHODS: Ninety-eight patients were classified into recovery and non-recovery groups according to the median 6-min walk distance (6MWD) at discharge. RESULTS: Logistic regression analysis revealed that pre-post change in knee extensor strength (ΔKES) and hematopoietic cell transplantation comorbidity index were useful predictors of recovery of exercise tolerance at discharge and moderate predictors of 6MWD recovery in the early post-transplant period. Receiver operating characteristic analysis showed that pre-transplant ΔKES was an accurate predictor of 6MWD recovery in the early post-transplant period. The cutoff point for ΔKES calculated using the Youden index was - 1.17 Nm/kg. CONCLUSIONS: The results of this study emphasize the importance of the need for programs designed to prevent muscle weakness in the early period after allo-HSCT. The results from markers of recovery of exercise tolerance are promising and can be used for patient education in rehabilitation programs after allo-HSCT.
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Tolerancia al Ejercicio , Trasplante de Células Madre Hematopoyéticas , Tolerancia al Ejercicio/fisiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Debilidad Muscular , Estudios Retrospectivos , Trasplante Homólogo/métodosRESUMEN
A 78-year-old man presented with hypercalcemia and renal disease with high serum IgG4 and positive myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA), exhibiting sarcoidosis-like chest findings. A renal biopsy revealed tubulointerstitial nephritis, membranous nephropathy (MN), and sub-capsular lymphoid aggregates without fulfilling the diagnostic criteria of IgG4-related disease or sarcoidosis. Steroid therapy ameliorated the serological and renal abnormalities. After 5 years, following gradual increases in the neutrophil count and upper respiratory infection (URI), necrotizing crescentic glomerulonephritis (NCGN) developed with an increased serum MPO-ANCA level. These results suggest that in the presence of MPO-ANCA in immune senescence, the persistent neutrophil increase with URI may lead to the development of NCGN.
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Glomerulonefritis Membranosa , Glomerulonefritis , Anciano , Anticuerpos Anticitoplasma de Neutrófilos , Glomerulonefritis/complicaciones , Glomerulonefritis/diagnóstico , Humanos , Riñón , Masculino , PeroxidasaRESUMEN
BACKGROUND: Acute necrotizing encephalopathy (ANE) is a severe encephalopathy associated with acute viral infection. While most ANE cases are sporadic, pathogenic variants in the gene RAN binding protein 2 (RANBP2) have been identified as a major cause of familial or recurrent ANE (ANE1). Although sporadic ANE predominantly affects Asian children, ANE1 is very rare in east Asia. CASE REPORT: A 1-year-7-month-old boy, born to unrelated Japanese parents, presented with a seizure and impaired consciousness after 3â¯days of fever. Brain magnetic resonance imaging (MRI) showed a characteristic involvement of the bilateral thalami, external capsules, insular cortices, and brainstem, suggesting ANE. He received intravenous steroids. Two months later, he had another episode of acute encephalopathy during respiratory syncytial virus infection, from which he recovered relatively well. The recurrent encephalopathic episodes and the characteristic MRI suggested ANE1. Genetic analyses revealed two variants: a rare heterozygous missense variant of RANBP2 [c.1754C>T; p.Thr585Met], and a thermolabile polymorphism in carnitine palmitoyltransferase 2 (CPT2) [c. 1055T>G; p.Phe352Cys]. CONCLUSION: This is the first case of recurrent ANE with an RANBP2 mutation in Japan. The patient also harbored a CPT2 polymorphism that is linked to acute encephalopathy in Japanese patients. Thus, he had a genetic background with two susceptibility variants for acute encephalopathy, RANBP2 (frequent in the Caucasians), and CPT2 (frequent in the Japanese). Further studies are needed to fully discover the genetic predisposition to familial or recurrent ANE in the Asian population.
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Encefalopatías/genética , Encefalopatías/patología , Carnitina O-Palmitoiltransferasa/genética , Chaperonas Moleculares/genética , Proteínas de Complejo Poro Nuclear/genética , Pueblo Asiatico , Humanos , Lactante , Japón , Leucoencefalitis Hemorrágica Aguda/genética , Leucoencefalitis Hemorrágica Aguda/patología , Masculino , Necrosis , RecurrenciaRESUMEN
PURPOSE: The purpose of this study was to clarify the independent factors related to patient-reported physical functioning (PF) scores at discharge of patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 103 patients who underwent allo-HSCT were included in this cross-sectional study. As a screening method, a single regression analysis was conducted with the PF domain in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 at discharge as the dependent variable, and body mass index, adverse events related to HSCT, and objective physical functions as independent variables. Multiple regression analysis was performed with PF as the dependent variable and variables that passed the screening by single regression analysis and confounders as independent variables. RESULTS: The mean PF score at discharge of the patients was 76.5 (standard deviation: 15.2). Based on the results of screening by the single regression analysis, length of stay, infections (+ / -), acute graft-versus-host disease grade, brief fatigue inventory score (BFI), knee extensor strength, and 6-min walk distance (6MWD) were included in the multiple regression analysis. BFI (B = - 11.94, p < 0.001) and 6MWD (per 10 m) (B = 0.56, p = 0.001) were extracted as significant independent variables governing the PF at discharge in the multiple regression model (adjusted R2 = 0.59). CONCLUSION: Higher exercise tolerance and lower fatigue in patients who underwent allo-HSCT were associated independently with patient-reported better PF scores at discharge.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Estudios Transversales , Humanos , Alta del Paciente , Medición de Resultados Informados por el Paciente , Calidad de VidaAsunto(s)
Obstrucción de las Vías Aéreas , Bronquitis , Eosinófilos/inmunología , Trampas Extracelulares , Granulocitos/inmunología , Gripe Humana , Moco , Obstrucción de las Vías Aéreas/inmunología , Obstrucción de las Vías Aéreas/metabolismo , Obstrucción de las Vías Aéreas/patología , Asma/diagnóstico , Asma/inmunología , Bronquitis/complicaciones , Bronquitis/etiología , Bronquitis/inmunología , Bronquitis/patología , Agregación Celular/inmunología , Muerte Celular , Niño , Cromatina/metabolismo , Trampas Extracelulares/inmunología , Trampas Extracelulares/metabolismo , Glicoproteínas/aislamiento & purificación , Humanos , Hipersensibilidad/diagnóstico , Hipersensibilidad/inmunología , Subtipo H1N2 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/complicaciones , Gripe Humana/diagnóstico , Gripe Humana/inmunología , Gripe Humana/terapia , Lisofosfolipasa/aislamiento & purificación , Masculino , Moco/diagnóstico por imagen , Moco/enzimología , Moco/inmunología , Neutrófilos/inmunología , Factores de RiesgoRESUMEN
Syntaxin-binding protein 1 (STXBP1; also called MUNC18-1), encoded by STXBP1, is an essential component of the molecular machinery that controls synaptic vesicle docking and fusion. De novo pathogenic variants of STXBP1 cause a complex set of neurological disturbances, namely STXBP1 encephalopathy (STXBP1-E) that includes epilepsy, neurodevelopmental disorders and neurodegeneration. Several animal studies have suggested the contribution of GABAergic dysfunction in STXBP1-E pathogenesis. However, the pathophysiological changes in GABAergic neurons of these patients are still poorly understood. Here, we exclusively generated GABAergic neurons from STXBP1-E patient-derived induced pluripotent stem cells (iPSCs) by transient expression of the transcription factors ASCL1 and DLX2. We also generated CRISPR/Cas9-edited isogenic iPSC-derived GABAergic (iPSC GABA) neurons as controls. We demonstrated that the reduction in STXBP1 protein levels in patient-derived iPSC GABA neurons was slight (approximately 20%) compared to the control neurons, despite a 50% reduction in STXBP1 mRNA levels. Using a microelectrode array-based assay, we found that patient-derived iPSC GABA neurons exhibited dysfunctional maturation with reduced numbers of spontaneous spikes and bursts. These findings reinforce the idea that GABAergic dysfunction is a crucial contributor to STXBP1-E pathogenesis. Moreover, gene expression analysis revealed specific dysregulation of genes previously implicated in epilepsy, neurodevelopment and neurodegeneration in patient-derived iPSC GABA neurons, namely KCNH1, KCNH5, CNN3, RASGRF1, SEMA3A, SIAH3 and INPP5F. Thus, our study provides new insights for understanding the biological processes underlying the widespread neuropathological features of STXBP1-E.
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Encefalopatías , Células Madre Pluripotentes Inducidas , Animales , Encefalopatías/genética , Encefalopatías/metabolismo , Neuronas GABAérgicas/metabolismo , Expresión Génica , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Proteínas Munc18/genética , Proteínas Munc18/metabolismoAsunto(s)
Traumatismos de los Pies , Osteomielitis , Infecciones por Pseudomonas , Antibacterianos/uso terapéutico , Traumatismos de los Pies/tratamiento farmacológico , Humanos , Osteomielitis/diagnóstico , Osteomielitis/tratamiento farmacológico , Infecciones por Pseudomonas/diagnóstico , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosaRESUMEN
Endochondral bone formation is fundamental for skeletal development. During this process, chondrocytes undergo multiple steps of differentiation and coordinated transition from a proliferating to a hypertrophic stage, which is critical to advance skeletal development. Here, we identified the transcription factor Dmrt2 (double-sex and mab-3 related transcription factor 2) as a Sox9-inducible gene that promotes chondrocyte hypertrophy in pre-hypertrophic chondrocytes. Epigenetic analysis further demonstrated that Sox9 regulates Dmrt2 expression through an active enhancer located 18 kb upstream of the Dmrt2 gene and that this enhancer's chromatin status is progressively activated through chondrocyte differentiation. Dmrt2-knockout mice exhibited a dwarf phenotype with delayed initiation of chondrocyte hypertrophy. Dmrt2 augmented hypertrophic chondrocyte gene expression including Ihh through physical and functional interaction with Runx2. Furthermore, Dmrt2 deficiency reduced Runx2-dependent Ihh expression. Our findings suggest that Dmrt2 is critical for sequential chondrocyte differentiation during endochondral bone formation and coordinates the transcriptional network between Sox9 and Runx2.
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Huesos/metabolismo , Condrocitos/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Proteínas de Unión al ADN/metabolismo , Enanismo/metabolismo , Osteogénesis , Factor de Transcripción SOX9/metabolismo , Factores de Transcripción/metabolismo , Animales , Huesos/patología , Huesos/fisiopatología , Línea Celular Tumoral , Condrocitos/patología , Condrogénesis , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Proteínas de Unión al ADN/genética , Modelos Animales de Enfermedad , Enanismo/genética , Enanismo/patología , Enanismo/fisiopatología , Epigénesis Genética , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Hipertrofia , Ratones Endogámicos C57BL , Ratones Noqueados , Factor de Transcripción SOX9/genética , Transducción de Señal , Factores de Transcripción/genética , Transcripción GenéticaRESUMEN
As the proportion of long-term survivors after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is on the rise, it is essential to consider the significance of quality of life (QOL), including reintegration with society (returning to school or work). This retrospective cohort study aims to illustrate the precise epidemiology of social reintegration later after allo-HSCT and determine its predictive indicators. We enrolled 56 patients, and 40 patients (71%) attained social reintegration at 2 years post-HSCT. Reintegration failure markedly correlated with an inferior performance status and concurrent chronic graft-versus-host disease. In non-reintegrated patients, the physical function at discharge measured by the 6-min walking distance (6MWD) was markedly decreased. On the multivariate risk analyses, sex (female; odds ratio (OR) 0.07; 95% confidence interval (CI) 0.01-0.54; p = 0.01), HCT-CI (≥ 2; OR 0.10; 95% CI 0.01-0.84; p = 0.03), and change in 6MWD (per 5% increase; OR 1.47; 95% CI 1.01-2.13; p = 0.04) were significant predictors of later social reintegration. This study suggests that a multidisciplinary strategy including rehabilitation is essential, especially in patients with poor predictive markers at an early phase, and we should consider suitable rehabilitation programs to prevent a decline in exercise tolerance and improve social reintegration and overall QOL in patients after allo-HSCT.
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Tolerancia al Ejercicio , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Probabilidad , Calidad de Vida , Estudios Retrospectivos , Trasplante Homólogo , Adulto JovenRESUMEN
The pneumococcal conjugate vaccines successfully decreased the incidence of invasive pneumococcal diseases and pneumococcal antibiotic resistance. However, they also led to serotype replacements. According to a report by the National Institute of Infectious Diseases (NIID) in 2017, 96% of pneumococcal isolates obtained from children with IPD aged < 5 years were non-PCV13 serotypes. Here, we report the case of a Japanese immunocompetent and vaccinated child who developed refractory meningitis caused by Streptococcus pneumoniae nonvaccine serotype 10A. PCR revealed genotypic penicillin-resistant Streptococcus pneumoniae (gPRSP) with triple mutations (pbp1a + 2b + 2x). Multilocus sequence typing identified the strain as a sequence type (ST) 11189. The ST11189 strain has not been reported in Japan, but it has recently been reported as a cause of invasive infections in Korea. The clinical course was complicated by the development of brain and subdural abscesses that necessitated prolonged antibiotic treatment and multiple burr hole drainages. Unfortunately, the neurological sequelae persisted. Continued molecular surveillance is needed for monitoring emerging virulent clinical strains.