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IMPORTANCE: Clarifying the relationship between kindergarteners' characteristics and their future handwriting performance is beneficial for the early detection of children at risk of handwriting difficulties. OBJECTIVE: To determine which visual-perceptual and motor skills and behavioral traits significantly predict kindergartners' Chinese handwriting legibility and speed in the first grade. DESIGN: One-year longitudinal, observational design. SETTING: Kindergarten and elementary schools. PARTICIPANTS: One hundred six kindergarten children (53 boys and 53 girls; ages 5 or 6 yr) were recruited. OUTCOMES AND MEASURES: The participants completed two subtests of the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition, Test of Visual Perceptual Skills-Third Edition, Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery™ VMI), and the Attention-Deficit/Hyperactivity Disorder Test-Chinese Version in kindergarten. Their handwriting legibility (character accuracy and construction) and speed were assessed by investigator-developed Chinese handwriting tests in the first grade. RESULTS: Multivariate regression analyses indicated the independent predictive power of spatial relationships (p = .042) and inattention (p = .004) for character accuracy. Visual-motor integration (VMI; p = .008) and inattention (p = .002) were the key predictors of character construction. Manual dexterity (p = .001) was the only significant predictor of writing speed. CONCLUSIONS AND RELEVANCE: Kindergarteners who perform poorly in spatial relationships, VMI, manual dexterity, and attention are likely to have less legible Chinese handwriting and slow writing speed in first grade. Plain-Language Summary: Children's visual-perceptual and motor skills and behavioral traits in kindergarten can predict their Chinese handwriting legibility and speed in first grade. This study found that kindergarteners who performed poorly in spatial relationships, VMI, manual dexterity, and attention were likely to have less legible Chinese handwriting and slow writing speed in the first grade.
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Destreza Motora , Instituciones Académicas , Niño , Femenino , Humanos , Masculino , Escolaridad , Escritura Manual , Lenguaje , PreescolarRESUMEN
IMPORTANCE: Few predictive models for later handwriting difficulties have been developed for kindergarteners. OBJECTIVE: To develop a nomogram for the purpose of detecting the risk of later poor Chinese handwriting among Taiwanese kindergarteners. DESIGN: One-year prospective longitudinal, observational study. SETTING: Kindergarten and elementary school. PARTICIPANTS: One hundred fifty-six kindergarteners were included. In first grade, they were grouped into the normal and poor handwriting groups on the basis of handwriting performance in first grade. OUTCOMES AND MEASURES: Participants received fine motor (FM), visual-perceptual (VP), and visual-motor integration tests in kindergarten and handwriting assessments in first grade. RESULTS: Logistic regression results indicated that younger age at school entry and lower scores on measures of FM and VP in kindergarten increased the risk for later poor handwriting. The area under the receiver operating characteristic curve in the nomogram built with these risk factors was .75, indicating that the nomogram had acceptable diagnostic value. CONCLUSIONS AND RELEVANCE: This nomogram could be used as a screening tool to detect kindergarteners at risk of poor Chinese handwriting in first grade. WHAT THIS ARTICLE ADDS: This study is the first to establish a nomogram constructed with significant predictors in kindergarten of a child's probability of poor handwriting later in first grade. This predictive nomogram may help occupational therapists, educators, and parents identify at-risk kindergarteners early for the purpose of early interventions to prevent later poor Chinese handwriting.
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Escritura Manual , Nomogramas , Niño , Humanos , Terapeutas Ocupacionales , Estudios Prospectivos , Instituciones AcadémicasRESUMEN
OBJECTIVES: Critical illnesses caused by undiagnosed genetic conditions are challenging in PICUs. Whole-exome sequencing is a powerful diagnostic tool but usually costly and often fail to arrive at a final diagnosis in a short period. We assessed the feasibility of our whole-exome sequencing as a tool to improve the efficacy of rare diseases diagnosis for pediatric patients with severe illness. DESIGN: Observational analysis. METHOD: We employed a fast but standard whole-exome sequencing platform together with text mining-assisted variant prioritization in PICU setting over a 1-year period. SETTING: A tertiary referral Children's Hospital in Taiwan. PATIENTS: Critically ill PICU patients suspected of having a genetic disease and newborns who were suspected of having a serious genetic disease after newborn screening were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Around 50,000 to 100,000 variants were obtained for each of the 40 patients in 5 days after blood sampling. Eleven patients were immediately found be affected by previously reported mutations after searching mutation databases. Another seven patients had a diagnosis among the top five in a list ranked by text mining. As a whole, 21 patients (52.5%) obtained a diagnosis in 6.2 ± 1.1 working days (range, 4.3-9 d). Most of the diagnoses were first recognized in Taiwan. Specific medications were recommended for 10 patients (10/21, 47.6%), transplantation was advised for five, and hospice care was suggested for two patients. Overall, clinical management was altered in time for 81.0% of patients who had a molecular diagnosis. CONCLUSIONS: The current whole-exome sequencing algorithm, balanced in cost and speed, uncovers genetic conditions in infants and children in PICU, which helps their managements in time and promotes better utilization of PICU resources.
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Secuenciación del Exoma/métodos , Enfermedades Genéticas Congénitas/diagnóstico , Niño , Preescolar , Toma de Decisiones Clínicas , Enfermedad Crítica/terapia , Humanos , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Secuenciación del Exoma/estadística & datos numéricosRESUMEN
BACKGROUND: While enzyme replacement therapy (ERT) has been shown to improve endurance and joint mobility for patients with mucopolysaccharidoses (MPS) I, II, IVA and VI, the impact of ERT on cardiac abnormalities remains uncertain. METHODS: Medical records and echocardiograms of 28 Taiwanese MPS patients (9 with MPS I, 7 with MPS II, 7 with MPS IVA, and 5 with MPS VI) treated with ERT for 1-10.8years were retrospectively reviewed. RESULTS: At start of ERT, z scores>2 were identified in 46% and 75% for left ventricular mass index (LVMI) and interventricular septum thickness in diastole (IVSd) in these patients, respectively. Twenty-four patients (86%) had valvular heart disease. After ERT, the mean IVSd z score of all patients decreased significantly from 3.87 to 2.57 (p=0.016). For 11 patients starting ERT before 12years of age, z scores for both LVMI and IVSd decreased significantly (p<0.01) after ERT. However, the condition of valve regurgitation or stenosis did not show improvement despite ERT. CONCLUSIONS: ERT was shown to be an effective therapy for reducing cardiac hypertrophy, with best results seen when ERT was started at an early age. ERT, however, had little impact on valvular heart disease.
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Terapia de Reemplazo Enzimático , Cardiopatías/diagnóstico , Cardiopatías/etiología , Corazón/fisiopatología , Mucopolisacaridosis/complicaciones , Mucopolisacaridosis/terapia , Miocardio/patología , Adolescente , Adulto , Niño , Preescolar , Ecocardiografía , Electrocardiografía , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Mucopolisacaridosis/diagnóstico , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To determine the benefit of newborn screening for the long-term prognosis of patients with classic infantile-onset Pompe disease (IOPD). STUDY DESIGN: A cohort of patients with classic IOPD were diagnosed by newborn screening, treated with recombinant human acid α-glucosidase (rhGAA), and followed prospectively. Outcome measurements included survival, left ventricular mass, serum creatinine kinase, motor function, mental development, and systemic manifestations. RESULTS: Ten patients who presented with left ventricular hypertrophy at diagnosis received rhGAA infusions starting at a median age of 16 days (6-34 days). All patients were cross-reactive immunologic material-positive. After a median treatment time of 63 months (range 28-90 months), all could walk independently, and none required mechanical ventilation. All patients had motor capability sufficient for participating in daily activities, but muscle weakness over the pelvic girdle appeared gradually after 2 years of age. Ptosis was present in one-half of the patients, and speech disorders were common. Anti-rhGAA antibody titers were low (median maximal titer value 1:1600, range: undetectable â¼ 1:12,800). CONCLUSION: By studying patients treated since birth who have no significant anti-rhGAA antibody interference, this prospective study demonstrates that the efficacy of rhGAA therapy is high and consistent for the treatment of classic IOPD. This study also exposes limitations of rhGAA treatment. The etiology of the manifestations in these early-treated patients will require further study.
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Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico , Tamizaje Neonatal/métodos , alfa-Glucosidasas/uso terapéutico , Edad de Inicio , Femenino , Estudios de Seguimiento , Enfermedad del Almacenamiento de Glucógeno Tipo II/tratamiento farmacológico , Enfermedad del Almacenamiento de Glucógeno Tipo II/epidemiología , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Pronóstico , Estudios Prospectivos , Proteínas Recombinantes , Tasa de Supervivencia/tendencias , Taiwán/epidemiología , Factores de TiempoRESUMEN
BACKGROUND/AIMS: During the resolution phase of inflammation, release of "find-me" signals by apoptotic cells is crucial in the chemoattraction of macrophages toward apoptotic cells for subsequent phagocytosis, in which microparticles derived from apoptotic cells (apo-MPs) are involved. A recent study reports that CX3CL1 is released from apoptotic cells to stimulate macrophages chemotaxis. In this study, we investigated the role of CX3CL1 in the apo-MPs in the cell-cell interaction between alveolar macrophage NR8383 cells and apoptotic all-trans retinoic acid-treated NB4 (ATRA-NB4) cells. METHODS/RESULTS: Apoptotic ATRA-NB4 cells and their conditioning medium (CM) enhanced the chemoattraction of NR8383 cells as well as their phagocytosis activity in engulfing apoptotic ATRA-NB4 cells. The levels of CX3CL1(+) apo-MPs and CX3CL1 were rapidly elevated in the CM of ATRA-NB4 cell culture after induction of apoptosis. Both exogenous CX3CL1 and apo-MPs enhanced the transmigration of NR8383 cells toward apoptotic ATRA-NB4 cells. This pro-transmigratory activity was able to be partially inhibited either by blocking the CX3CR1 (CX3CL1 receptor) of NR8383 cells with its specific antibody or by blocking the surface CX3CL1 of apo-MPs with its specific antibody before incubating these apo-MPs with NR8383 cells. CONCLUSION: CX3CL1(+) apo-MPs released by apoptotic cells mediate the chemotactic transmigration of alveolar macrophages.
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Apoptosis , Micropartículas Derivadas de Células/metabolismo , Quimiocina CX3CL1/metabolismo , Quimiotaxis , Leucemia Promielocítica Aguda/metabolismo , Macrófagos Alveolares/metabolismo , Proteínas de Neoplasias/metabolismo , Animales , Línea Celular Tumoral , Micropartículas Derivadas de Células/patología , Humanos , Leucemia Promielocítica Aguda/patología , Macrófagos Alveolares/patología , Ratas , Ratas Sprague-Dawley , Tretinoina/farmacologíaRESUMEN
Mechanical ventilation using endotracheal tube (ETT) intubation is crucial in saving life but may also cause ventilator-associated pneumonia resulting in morbidity and mortality. The purpose of this study was to examine the effects of intubation duration on pathogen colonization rates of ETT cuff region, and its association with the subsequent re-intubation and tracheostomy. We enrolled 92 patients who were successfully weaned from ventilator and were extubated within 20 days of intubation duration. Patients were divided into Group I and II based on intubation for 1-9 days and 10-20 days, respectively. Pathogen colonization over ETT cuff region and extra-cuff region (including sputum and ETT aspirates) were assessed. As compared to Group I patients, Group II patients had a significant higher pathogen colonization rate (100% vs. 69.2%; P < 0.001) in the ETT cuff samples, but not in the extra-cuff samples (92.6% vs. 84.8%; P = 0.442). Further studies demonstrated that there was no difference between Group I and II patients in the percentages of patients with the same pathogen over both the cuff and extra-cuff samples (35.5% vs. 30.8%; P = 0.925), suggesting that the increased pathogen colonization rate over the ETT cuff region was least likely from the extra-cuff region. In addition, the results showed that longer intubation was also associated with increased tracheostomy rate from 9.3% to 28.9% for Group I and Group II respectively (P = 0.025). We conclude that longer intubation has a higher pathogen colonization rate over the ETT cuff region in patients receiving mechanical ventilation support; longer intubation also increases the trend of receiving re-intubation and tracheostomy. Our findings indicate that it is crucial to remove ETT as soon as possible and perform pathogen culture over the ETT cuff regions immediately after extubation.
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Contaminación de Equipos/estadística & datos numéricos , Control de Infecciones , Intubación Intratraqueal/efectos adversos , Respiración Artificial/efectos adversos , Traqueostomía/efectos adversos , Anciano , Anciano de 80 o más Años , Femenino , Infecciones por Bacterias Gramnegativas/epidemiología , Humanos , Infecciones por Klebsiella/epidemiología , Klebsiella pneumoniae/aislamiento & purificación , Masculino , Persona de Mediana Edad , Factores de Riesgo , Infecciones por Serratia/epidemiología , Serratia marcescens/aislamiento & purificación , Stenotrophomonas maltophilia/aislamiento & purificaciónRESUMEN
Annexin A1 (AnxA1), originally identified as a glucocorticoid-regulated protein, is an impor- tant endogenous anti-inflammatory mediator during the resolution phase of inflammation, and its cir- culating level has been rarely studied in sepsis patients. Glucocorticoid has been extensively used in treating patients with sepsis. However, it is unclear whether endogenous cortisol or exogenous glucocor- ticoid contributes to the regulation of AnxA1 levels in peripheral blood of sepsis patients. The aim of this study was to investigate: [1] serial changes over time in the plasma levels of AnxA1 and cortisol in sepsis patients; and [2] prognostic value of AnxA1 level in the survival of sepsis patients. Fifty-eight adult sepsis patients admitted to an intensive care unit (ICU) were enrolled. The plasma levels of cortisol and AnxA1 were determined by specific enzyme-link immunosorbent assay. Results show that the median daily levels of cortisol at the 1st, 3rd, 5th and 7th day after admission to ICU were signifi- cantly elevated over the cortisol level of the control subjects. However, the AnxA1 level was elevated in only thirty-three patients (56%) over the observation period. There was no significant correlation between cortisol levels and AnxA1 levels. Further analysis indicated that steroid treatment resulted in significant elevation of the cortisol level over time, but did not affect the AnxA1 level. AnxA1 levels were also not statistically different between surviving and non-surviving patients. In conclusions, the circu- lating level of AnxA1 is elevated in a subgroup of sepsis patients, and the AnxA1 level does not correlate with the cortisol level in the peripheral blood of sepsis patients.
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Anexina A1/sangre , Hidrocortisona/sangre , Sepsis/sangre , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sepsis/mortalidadRESUMEN
Annexin A1 (AnxA1) is an important anti-inflammatory mediator during granulocytic differentiation in all trans-retinoic acid (ATRA) treated acute promyelocytic leukemic (APL) cells. Dexamethasone has been used successfully to prevent complications in ATRA-treated APL patients, although its mechanism of action is still not clear. In the present study, we have examined the effect of dexamethasone on the modulation of AnxA1 in ATRA-APL NB4 (ATRA-NB4) cells, ATRA-NB4 cells-derived microparticles (MPs) and its role during cell-cell interaction between ATRA-NB4 cells and endothelial cells. Our results have shown that dexamethasone can inhibit the percentage of ATRA-NB4 cells expressing surface AnxA1 and its receptor FPR2/ALX in a time-dependent manner based on flow cytometric analysis. However, dexamethasone treatment of ATRA-NB4 cells has no significant effect on the level of AnxA1 mRNA, the total cellular level of AnxA1 protein or the release of AnxA1 from these cells, as determined by RT-PCR, Western blotting, and ELISA, respectively. Further studies demonstrate that dexamethasone is able to significantly inhibit the adhesion of ATRA-NB4 cells to endothelial cells, and this anti-adhesive effect can be inhibited if the cells were pre-treated with a neutralizing antibody specific for AnxA1. Finally, dexamethasone also enhances the release of AnxA1-containing MPs from ATRA-NB4 cells which can in turn prevent the adhesion of the ATRA-NB4 cells to endothelial cells. We conclude that biologically active AnxA1 originating from dexamethasone-treated ATRA-APL cells and their MPs plays an anti-adhesive effect and this contributes to inhibit the adhesion of ATRA-APL cell to endothelial cells.
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Anexina A1/metabolismo , Adhesión Celular/efectos de los fármacos , Dexametasona/farmacología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Leucemia Promielocítica Aguda/metabolismo , Anexina A1/biosíntesis , Anexina A1/genética , Anticuerpos Neutralizantes/inmunología , Diferenciación Celular , Línea Celular Tumoral , Micropartículas Derivadas de Células , Humanos , Mediadores de Inflamación , ARN Mensajero/biosíntesis , Tretinoina/farmacologíaRESUMEN
BACKGROUND: Late-preterm and early-term births constitute a significant proportion of live births. However, handwriting skills of these two populations remain unclear. We aimed to investigate their risk for poor Chinese handwriting in grade two. METHODS: In this observational study, 185 second graders born late preterm (34+0-36+6 weeks' gestation, n = 54), early term (37+0-38+6 weeks' gestation, n = 56), and full term (39+0-41+6 weeks' gestation, n = 75) without any intervention or diagnosis related to developmental delays were included. Their handwriting performance was rated by class teachers using the Chinese Handwriting Evaluation Form (CHEF), which is a standardized handwriting scale including five handwriting dimensions (construction, accuracy, directionality, speed, and pencil grasp). RESULTS: After controlling for demographic risk factors, the late-preterm born group had a greater risk of having worse performance in the full form (adjusted odds ratio [aOR] = 3.93; p = .038) and construction dimension (aOR = 4.77; p = .009) of the CHEF than peers born at full term, whereas the risks were comparable for the early- and full-term born groups (aOR = 0.14-1.90; p = .073-0.453 in the handwriting dimensions). CONCLUSIONS: Late-preterm but not early-term born children were found to be at higher risk for poor Chinese handwriting in grade two. They particularly have difficulty with spatial construction including size, spacing, and alignment of Chinese characters and components that may influence handwriting legibility.
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Nacimiento Prematuro , Recién Nacido , Femenino , Humanos , Niño , Escritura Manual , Edad GestacionalRESUMEN
Membranous CD14 is crucial in the phagocytic activity of neutrophils. However, the role of CD14(+) microparticles (MPs) derived from apoptotic neutrophils (apo-MP) during the phagocytic process is not clear. All trans-retinoic acid (ATRA) induces acute promyelocytic leukemic NB4 cells along granulocytic differentiation. In this study, we investigated the role of CD14(+)apo-MP in the cell-cell interaction during the phagocytic process of apoptotic cells by viable ATRA-NB4 cells. We firstly demonstrate that CD14 expression and phagocytic activity of NB4 cells were upregulated simultaneously after ATRA treatment in a time-dependent manner, and both were significantly enhanced via concurrent lipopolysaccharide treatment. The phagocytic activity of ATRA-NB4 cells and lipopolysaccharide-treated ATRA-NB4 cells were both significantly attenuated by pre-treating cells with an antibody specific to either CD14 or TLR4. Further flow cytometric analysis demonstrates that apoptotic ATRA-NB4 cells release CD14(+)apo-MP in an idarubicin dosage-dependent manner. Both CD14 expression and the phagocytic activity of viable ATRA-NB4 cells were significantly enhanced after incubation with apo-MP harvested from apoptotic ATRA-NB4 cells, and the apo-MP-enhanced phagocytic activity was significantly attenuated by pre-treating apo-MP with an anti-CD14 antibody before incubation with viable cells. We conclude that CD14(+)apo-MP derived from apoptotic ATRA-NB4 cells promotes the phagocytic activity of viable ATRA-NB4 cells in engulfing apoptotic cells.
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Leucemia Promielocítica Aguda , Humanos , Leucemia Promielocítica Aguda/metabolismo , Lipopolisacáridos/farmacología , Tretinoina/farmacología , Fagocitosis , ApoptosisRESUMEN
Precocious puberty in girls is defined as the onset of pubertal changes before 8 years of age, and gonadotropin-releasing hormone (GnRH) agonist treatment is available for central precocious puberty (CPP). The gold standard for diagnosing CPP is the GnRH stimulation test. However, the GnRH stimulation test is time-consuming, costly, and requires repeated blood sampling. We aimed to develop an artificial intelligence (AI) prediction model to assist pediatric endocrinologists in decision making regarding the optimal timing to perform the GnRH stimulation test. We reviewed the medical charts of 161 girls who received the GnRH stimulation test from 1 August 2010 to 31 August 2021, and we selected 15 clinically relevant features for machine learning modeling. We chose the models with the highest area under the receiver operating characteristic curve (AUC) to integrate into our computerized physician order entry (CPOE) system. The AUC values for the CPP diagnosis prediction model (LH ≥ 5 IU/L) were 0.884 with logistic regression, 0.912 with random forest, 0.942 with LightGBM, and 0.942 with XGBoost. For the Taiwan National Health Insurance treatment coverage prediction model (LH ≥ 10 IU/L), the AUC values were 0.909, 0.941, 0.934, and 0.881, respectively. In conclusion, our AI predictive system can assist pediatric endocrinologists when they are deciding whether a girl with suspected CPP should receive a GnRH stimulation test. With proper use, this prediction model may possibly avoid unnecessary invasive blood sampling for GnRH stimulation tests.
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BACKGROUND: Infants and children with feeding difficulties have swallowing dysfunction and high risk of aspiration, which could be silent without choking, resulting in recurrent pneumonia and long-term respiratory morbidity. Videofluoroscopic swallow study (VFSS) is a useful tool for real-time visualization of the swallowing process and airway aspiration. This study reported a single-institutional 10-year experience of VFSS in pediatric patients with feeding difficulties and the efficacy of swallowing therapy. METHODS: From 2011 to 2020, 30 infants and children with feeding difficulties received VFSS examinations in a medical center at a median age of 19 months (range 7 days-8 years). The images of the swallowing process (oral phase, triggering of pharyngeal swallowing, and pharyngeal phase) under videofluoroscopy were analyzed by a radiologist and a speech-language pathologist. Aspiration severity was assessed from VFSS observations and rated by an eight-point Penetration-Aspiration-Scale (PAS), with higher scores indicating increased severity. Swallowing therapy was performed by experienced speech-language therapists, and follow-up of oral feeding tolerance and risk of aspiration pneumonia was done. RESULTS: Of the 30 patients, 24 (80%) had neurological deficits. High PAS scores (6-8) were observed in 25 (83.4%) patients, and 22 had a PAS score of 8, indicating silent aspiration. Of the 25 patients with high PAS scores, 19 (76%) had neurological deficits, and 18 (72%) depended on tube feeding at a median age of 20 months. Swallowing problems occurred most frequently during the pharyngeal phase in the patients with high PAS scores. VFSS-based swallowing therapy improved oral feeding ability and reduced aspiration episodes. CONCLUSION: Infants and children with swallowing dysfunction and neurological deficits had high risk of severe aspiration. Swallowing problems in the pharyngeal phase were the most common VFSS findings in patients with severe aspiration. VFSS may help guide problem-oriented swallowing therapy to reduce the risk of recurrent aspiration.
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Obstrucción de las Vías Aéreas , Trastornos de Deglución , Humanos , Lactante , Niño , Recién Nacido , Deglución , Trastornos de Deglución/diagnóstico por imagen , Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , Nutrición Enteral , Estudios RetrospectivosRESUMEN
OBJECTIVE: Ribonuclease P RNA component H1 (RPPH1) is a long non-coding RNA (lncRNA) associated with cancer progression. Higher RPPH1 expression in breast and cervical cancer samples than that in normal tissues were observed through the lncRNASNP2 database; therefore, silencing RPPH1 expression might be a potential strategy for cancer treatments, even though RPPH1 is also an RNA subunit of ribonuclease P involved in processing transfer RNA (tRNA) precursors and the effect of RPPH1 knockdown is not yet fully understood. METHODS: Differentially expressed genes (DEGs) were identified through RNA sequencing in each shRNA-transfected RPPH1 knockdown MDA-MB-231, RPPH1 knockdown HeLa cell, and respective control cells, then the gene ontology enrichment analysis was performed by IPA and MetaCore database according to these DEGs, with further in vitro experiments validating the effect of RPPH1 silencing in MDA-MB-231 and HeLa cells. RESULTS: Hundreds of down-regulated DEGs were identified in RPPH1 knockdown MDA-MB-231 and HeLa cells while bioinformatics analysis revealed that these genes were involved in pathways related to immune response and cancerogenesis. Compared to mock- and vector-transfected cells, the production of mature tRNAs, cell proliferation and migration capacity were inhibited in RPPH1-silenced HeLa and MDA-MB-231 cells. Additionally, RPPH1 knockdown promoted G1 cell cycle arrest mainly through the down-regulation of cyclin D1, although glycolytic pathways were only affected in RPPH1 knockdown HeLa cells but not MDA-MB-231 cells. CONCLUSION: This study demonstrated that knockdown RPPH1 affected tRNA production, cell proliferation and metabolism. Our findings might provide insight into the role of RPPH1 in tumor development.
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Differentiation therapy with all-trans retinoic acid (ATRA) has been used successfully to treat acute promyelocytic leukemia (APL), but such treatment also causes differentiation syndrome (DS) by inducing APL cell infiltration into alveolar spaces. The mechanism underlying the clearance of infiltrated APL cells has not been investigated in detail. Lipoxin A(4) (LXA(4)) is an important anti-inflammatory mediator during the resolution of inflammation. In this study, the role of LXA(4) in the cell-cell interaction between alveolar macrophages (AMφ; NR8383 cells) and APL NB4 cells was investigated and found that conditioned medium (CM) harvested from ATRA-treated NR8383 (ATRA-NR8383) cells was able to induce the transmigration of ATRA-NB4 cells. However, the pro-migratory activity of CM was attenuated progressively when ATRA-NR8383 cells were co-cultured with increased cell dosages of apoptotic NB4 cells. A significantly higher amount of LXA(4) was released into the CM by ATRA-NR8383 cells when they were co-cultured with apoptotic ATRA-NB4 cells. Expression of a receptor for LXA(4) (ALX/FPR2) was enhanced in both ATRA-NB4 cells and ATRA-NR8383 cells. Exogenous LXA(4) treatment was able to inhibit the transmigration of ATRA-NB4 cells and induce the phagocytic clearance of apoptotic cells by ATRA-NR8383 cells. The anti-migratory activity of exogenous LXA(4) was attenuated by pre-treating ATRA-NB4 cells with an ALX/FPR2 inhibitor. We conclude that AMφ-derived LXA(4) plays an important role in the interaction between AMφ and APL cells and that this contributes to clearance of apoptotic APL cells.
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Comunicación Celular/fisiología , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patología , Lipoxinas/fisiología , Macrófagos Alveolares/fisiología , Fagocitosis/fisiología , Tretinoina/farmacología , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Comunicación Celular/efectos de los fármacos , Línea Celular Tumoral , Inhibición de Migración Celular/fisiología , Células Cultivadas , Técnicas de Cocultivo , Humanos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Lipoxinas/metabolismo , Macrófagos Alveolares/citología , Macrófagos Alveolares/efectos de los fármacos , Fagocitosis/efectos de los fármacos , RatasRESUMEN
Annexin A1 (AnxA1) originating from mature neutrophils and their microparticles (MPs) plays an important anti-inflammatory role during the resolution phase of inflammation. However, the role of AnxA1 during the process of granulocytic differentiation is still unknown. All-trans retinoic acid (ATRA) can induce acute promyelocytic leukemic (APL) cells to differentiate along the granulocytic lineage and has been used successfully in treating APL patients. In this study, we investigated whether or not AnxA1 contributed to the anti-inflammatory properties of ATRA-treated APL (NB4; ATRA-NB) cells using the transmigratory and adhesive assays. We found that ATRA was able to enhance the surface expression of AnxA1 and its receptor (FPR2/ALX) and the release of AnxA1-containing MPs from ATRA-NB4 cells, while the expression of annexin V was not elevated on the latter cells. Further studies demonstrated that exogenous AnxA1 could inhibit ATRA-NB4 cells in their transmigratory activity and adhesion to endothelial cells. In addition, the transmigratory activity of ATRA-NB4 cells can be significantly enhanced by pretreatment with a FPR2/ALX neutralizing antibody, suggesting that endogenous AnxA1 may contribute to the anti-migratory effects. Finally, ATRA-NB4-derived MPs could also inhibit recipient cells in their transmigratory and adhesive activities and these anti-inflammatory effects could be inhibited by pretreatment of MPs with a specific anti-AnxA1 antibody. Flowcytometry studies further demonstrated that FITC-labeled AnxA1 could be transported from MPs to the membrane of recipient ATRA-NB4 cells. We conclude that biologically active AnxA1 may play a role in the anti-inflammatory properties of ATRA-treated APL cells during the process of granulocytic differentiation.
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Anexina A1/metabolismo , Diferenciación Celular , Granulocitos/citología , Inflamación/metabolismo , Leucemia Promielocítica Aguda , Tretinoina/farmacología , Anexina A1/antagonistas & inhibidores , Anexina A1/inmunología , Anexina A5/metabolismo , Anticuerpos Antiidiotipos , Adhesión Celular/genética , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Linaje de la Célula , Micropartículas Derivadas de Células/metabolismo , Medios de Cultivo Condicionados , Células Endoteliales/citología , Células Endoteliales/metabolismo , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Granulocitos/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/metabolismo , Receptores de Formil Péptido/metabolismo , Receptores de Lipoxina/metabolismoRESUMEN
OBJECTIVE: To identify the influence of various physiological and behavioral factors on feeding performance of preterm infants in the transition to full oral feeding. METHODS: We retrospectively reviewed data from a feeding assessment conducted on 24 preterm infants born at 25-31 weeks without severe brain complications. RESULTS: Prolonged oxygen use and low current weight are two adverse factors for feeding efficiency (volume of milk ingested orally per minute in the initial 5 min of feeding) and proficiency (percentage of prescribed volume ingested orally over the entire feeding). Young post-menstrual age, low baseline oxygen saturation and high feeding efficiency were risk factors for oxygen desaturation during the initial feeding. CONCLUSION: Proper feeding strategies are needed for preterm infants with those disadvantageous factors to improve their early feeding performance.
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Conducta Alimentaria/fisiología , Edad Gestacional , Recien Nacido Prematuro , Peso al Nacer , Alimentación con Biberón , Femenino , Humanos , Recién Nacido , Masculino , Terapia por Inhalación de Oxígeno/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Conducta en la Lactancia/fisiologíaRESUMEN
"We undertook this study to investigate the adequate oxygen concentration that can be applied safely to the treatment of pneumothorax. Complete unilateral pneumothorax was induced artificially in rabbits, which were subsequently treated with various inspired oxygen fractions (FIO2; 21%, 60%, 80% or 100%). The pneumothorax resolution time was measured together with the levels of IL-1ß and IL-8 in broncho-alveolar lavage (BAL) and plasma samples. Furthermore, the lungs from these animals were examined for histolopathological evidence of oxygen toxicity. The results showed that the resolution time was significantly faster in the pneumothorax rabbits when treated with higher FIO2. Significantly higher levels of IL-1 ß were detected in BAL samples collected from the pneumothorax-rabbits that had received FIO2 at levels of either 80% or 100% (P < 0.05), but not in those with FIO2 at the 60% level. However, there was no significant change in the level of IL-8 in the BAL when the pneumothorax-rabbits were treated with different FIO2 levels. In addition, no evidence of oxygen toxicity was found when the lung tissues were examined. The data indicated that higher FIO2 treatment can accelerate the resolution of pneumothorax, but caution should be exercised with regard to associated oxygen toxicity when the FIO2 used is greater than 80%. We conclude that treatment with 60% FIO2 is an appropriate concentration for oxygen therapy for the treatment of pneumothorax in this model."
Asunto(s)
Oxígeno , Neumotórax , Animales , Interleucina-1beta , Interleucina-8 , Pulmón , Oxígeno/sangre , ConejosRESUMEN
BACKGROUND: Neonatal hypoglycemia is a common metabolic disorder in newborns, which may present with non-specific symptoms or even be asymptomatic. Current guidelines recommend screening for hypoglycemia in at-risk babies (late preterm, small for gestational age, large for gestational age, and infants of diabetic mothers). Past studies have suggested other potential risk factors, such as maternal obesity, gestational hypertension, cesarean section, etc. In this study, we aim to identify additional prenatal and perinatal maternal/fetal characteristics associated with early asymptomatic hypoglycemia in term and late preterm babies. METHODS: We performed a retrospective review on medical charts of all newborns, born between January, 2017 and December, 2020, in the well-baby newborn nursery of a tertiary medical center. We identified newborns who had received blood glucose concentration monitor after birth. Detailed prenatal and perinatal maternal/newborn information were collected for analysis. RESULTS: In the study period, 841 newborns had received blood glucose screening after birth. After matching by sex and indication for postnatal blood glucose screen (SGA, LGA, and GDM), 148 newborns were included in the "hypoglycemia group" and 296 newborns were included in the "euglycemia group". In the univariate analysis, parity, insulin treatment for gestational diabetes mellitus (GDM), and cesarean section were associated with an increased risk for neonatal hypoglycemia. Factors associated with decreased risk included higher gestational age, longer duration of skin-to-skin contact, neonatal hyperthermia, higher maternal labor pain score, and epidural anesthesia administration. By multivariable analysis, insulin treatment for GDM was identified as an independent factor associated with increased risk for neonatal hypoglycemia. CONCLUSION: Our study showed insulin treatment for GDM to be independently associated with neonatal hypoglycemia. Other risk factors noted in the univariate analysis, such as decreased skin-to-skin contact duration, hypothermia, Cesarean section, and preterm delivery, would require further investigation to confirm the findings.