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AIMS: The increasing prevalence of childhood obesity escalates the risk for related complications. Circulating microRNAs (miRNAs) have been suggested as good predictive markers of insulin resistance in those with obesity. The aim was to identify a circulating miRNA profile that reflects insulin resistance in prepubertal children with obesity. MATERIAL AND METHODS: Plasma miRNAs were measured in prepubertal children (n = 63, 5-9 years) using TaqMan Advanced miRNA Human Serum/Plasma plates and then were validated by RT-qPCR. Subjects were divided into normal weight (n = 20, NW) and overweight or obese (n = 43, OW/OB) groups according to their BMI z-scores. The OW/OB group was further subdivided into insulin sensitive or metabolically healthy obese (n = 26, MHO) and insulin resistant or metabolically unhealthy obese (n = 17, MUO) according to HOMA-IR. KEY FINDINGS: While no differences were observed in the fasting plasma glucose levels, serum insulin levels were significantly elevated in the OW/OB compared to the NW group. Of 188 screened miRNAs, eleven were differentially expressed between the NW and OW/OB groups. Validation confirmed increased circulating levels of miR-146a-5p and miR-18a-5p in the OW/OB group, which correlated with BMI z-score. Interestingly, miR-146a-5p was also correlated with HOMA-IR index. While only miR-18a-5p was upregulated in the OW/OB children, independently of their degree of insulin sensitivity, miR-146-5p, miR-423-3p and miR-152-3p were associated with insulin resistance. SIGNIFICANCE: The present study provides evidence of molecular alterations that occur early in life in prepubertal obesity. These alterations may potentially be crucial for targeted prevention or prompt precision therapeutic development and subsequent interventions.
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MicroARN Circulante , Resistencia a la Insulina , MicroARNs , Obesidad Infantil , Humanos , Niño , Resistencia a la Insulina/genética , MicroARN Circulante/genética , Obesidad Infantil/genética , Obesidad Infantil/epidemiología , Insulina , MicroARNs/genética , Índice de Masa CorporalRESUMEN
BACKGROUND: Various techniques are used across institutions for implantation of deep brain stimulation (DBS) leads. The most used techniques for each step include preoperative MRI fused to in-frame CT, intraoperative fluoroscopy, and postoperative CT, but postimplantation MRI also is used, as it was at our center. We present the quality assurance study performed at our institution after a change from postimplantation MRI performed across the hospital to postimplantation in room CT. METHODS: Retrospective chart review of 123 patients who underwent bilateral DBS leads placement without same-day generator placement that was performed. The patients were divided by the type of postoperative imaging that was obtained. Patients were excluded if a unilateral lead placement was performed, if the case was a revision of an existing lead or deviated from the normal protocol. Operative room times and procedure times for each group were analyzed with Wilcoxon rank sums test (WRST) to determine any significant differences between groups. RESULTS: Postoperative MRI was performed for 82 patients, while postoperative CT was performed for 41 patients. A WRST showed a significant reduction in both operative room time (209 min to 170 min, P < 0.0001) and procedure time (140 min to 126 min, P = 0.0019). CONCLUSION: In-room CT allowed for a significant reduction in operative room time. Lower operative room time has been associated with increased patient comfort, and decreased cost. CT did not alter the revision rate for procedures. The significant reduction in procedure time may be attributed to increased team familiarity with procedure over time.
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BACKGROUND: Medication refusal in children is largely driven by aversive taste profiles, which in turn influence adherence and therapeutic outcomes. However, there are no standardized methods for evaluating taste in young children. This study compares facial recognition technology with three hedonic visual scales in this population. METHODS: Children, 3-7 years of age, were enrolled with informed parental permission into an institutional review board-approved, double-blind, randomized investigation. Each child received three test articles: prednisone (bitter), simple syrup (sweet), and filtered water (neutral), with an appropriate washout. Facial recognition software (Noldus FaceReader 7) recorded facial expression and intensity for 30-60 s after administration. Participants subsequently rated taste using three hedonic scales (5-point Sjövall and 5- and 3-point TASTY) and responded to simple questions on their perception of the test article. Repeated measures analysis of variance and multiple regression analysis were used to explore associations between palatability measures. RESULTS: Twelve children (seven males: ten white and two black) completed the study without adverse effects. There were no significant differences in participant characteristics by randomization sequence. The three hedonic scales tracked similarly for each test substance, with correlations between the 5-point scales (r = 0.899) comparable to those between the 3- and 5-point scales (r = 0.860-0.903). Hedonic scales appeared more reliable in assessing taste response than facial recognition, which did not effectively discriminate positive and negative responses. CONCLUSIONS: Our experience suggests that the TASTY scales appear to offer the greatest promise for assessing palatability in future clinical use.
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Evaluación de Necesidades/normas , Gusto/fisiología , Niño , Preescolar , Método Doble Ciego , Femenino , Humanos , Masculino , Proyectos PilotoRESUMEN
There is a growing consensus that nutritional programming may persist and influence risk for several chronic diseases in adulthood. In the present study, we used urinary metabolic analysis in assessing diet effects on early-life metabolism. Urine samples from healthy three-month-old infants fed human milk (HM; n = 93), cow's milk-based infant formula [MF; n = 80], or soy protein-based infant formula (SF; n = 76) were analyzed with an untargeted metabolomics approach using GC-TOF MS. PLS-DA and ANOVA analyses were performed using MetaboAnalyst (v4.0). A total of 150 metabolites differed significantly among the feeding groups, including dietary-specific patterns of urinary metabolites of sugars, sugar alcohols, amino acids, and polyphenols. Urinary metabolites may mirror the infant's overall metabolism and serve as a noninvasive tool to examine the neonatal effects of diet on early-infant metabolism.
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Fórmulas Infantiles/química , Metaboloma/fisiología , Urinálisis , Animales , Bovinos , Dieta , Femenino , Humanos , Lactante , Masculino , Metabolómica , Leche , Leche Humana/química , Leche Humana/metabolismo , Proteínas de SojaRESUMEN
Background: Clindamycin's bitter taste and odor is known to affect treatment adherence in children. Recently, a formulation of clindamycin HCl complexed with ion exchange resin IRP 69 was shown to mask the bitter taste. Because of the potential benefit of this formulation for children, a pilot study using a porcine model was conducted to evaluate its relative bioavailability. Methods: A randomized two-way crossover study design using six (n = 6) healthy male piglets 10-12 kg was used to evaluate the absorption profiles and pharmacokinetic parameters of clindamycin from the resinate complex formulation (Test) compared to a commercialized reference suspension. A dose of 15 mg/kg was administered orally by gastric gavage to each piglet followed by repeated blood sampling over 12 h. A wash-out period of 48 h occurred between treatments. Plasma concentration vs. time data was analyzed by non-compartmental analysis. Results: The mean relative bioavailability of clindamycin from the resinate formulation was 78.8%. A two-tailed, paired Student t test yielded a p < 0.05 for AUC∞ and Tmax parameters. A two one-sided test (TOST) suggested a difference in AUC∞ and Cmax for the Test formulation compared to the reference formulation according to the FDA's criteria for bioequivalence. Conclusion: The bioavailability of clindamycin from this novel oral formulation supports continued evaluation of the drug in humans for potential pediatric applications.
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Clindamicina/farmacocinética , Resinas de Intercambio Iónico/farmacocinética , Suspensiones/farmacocinética , Gusto/efectos de los fármacos , Administración Oral , Animales , Antibacterianos/farmacocinética , Área Bajo la Curva , Disponibilidad Biológica , Química Farmacéutica/métodos , Estudios Cruzados , Semivida , Masculino , Proyectos Piloto , Porcinos , Equivalencia TerapéuticaRESUMEN
Background: Pulmonary exacerbations (PExs) are common in individuals with cystic fibrosis (CF). Data regarding outcomes of outpatient parenteral antimicrobial therapy (OPAT) in children are sparse. Methods: Retrospective data of PEx episodes treated in the hospital versus OPAT collected. Children ≤18 years were included. Outcome measures included FEV1, FVC, FEF25-75%P, time to the next PEx, and weight gain. Results: Eighty-three subjects with 290 PEx events were eligible. The hospital group had 242 and the OPAT group had 48 PEx events. The median age was 13.1 years for the OPAT and 13.4 years for the hospital group. Medicaid coverage was higher in the hospital group (82.2%) versus OPAT group (48.9%, P < 0.0001). The hospital group had lower FEV1%P on admission [72%P (interquartile range [IQR] = 59.7 and 84) versus 80%P (IQR = 70.7 and 89); P = 0.001] and at the end of treatment [86%P (IQR = 72 and 96.7) versus 92%P (IQR = 82 and 101); P = 0.003] in comparison with OPAT group. FEV1%P improved more in the hospital group, [12%P (IQR = 4 and 20)] versus in the OPAT group [8%P (IQR = 2 and 22.5); (P = 0.41)] but did not quite reach a statistically significant level. The hospital intravenous (IV) group gained more weight (P < 0.0001). There was no difference between the 2 groups in time to the first PEx (P = 0.47) and adverse events. Conclusion: OPAT was safe and comparable with hospital therapy in a select group of children with CF. Hospital IV should be considered for sicker children and families with limited resources.