Implementation of the Mind Youth Questionnaire (MY-Q) for routine health-related quality of life screening of adolescents with type 1 diabetes in a large tertiary care center.

OBJECTIVES: Prevalence of diabetes distress and mental health comorbidities among adolescents with type 1 diabetes (T1D) is high. Despite recommendations for routine psychosocial risk assessment, there is little guidance for their implementation. This study aims to describe the implementation and baseline outcomes of the Mind Youth Questionnaire (MY-Q), a validated psychosocial screening tool for health-related quality of life (QoL) including mood, among adolescents living with T1D. METHODS: Adolescents aged 13-18 years completed the MY-Q from October 1, 2019-April 1, 2023. Baseline characteristics, MY-Q results including categories flagged positive (noting possible areas of concern), debrief duration, and frequency of social work or mental health referral were collected and analyzed using descriptive statistics. RESULTS: A total of 343 adolescents (mean age 15.3 years; 52 % female) completed a baseline MY-Q. Median overall MY-Q debrief time (IQR) was 10.0 min (6.0, 20.0). About 290 (84.5 %) adolescents had at least one of seven categories flagged, most commonly "Family" (61 %). About 30 % of adolescents had "Mood" flagged, and 2.9 % of adolescents were referred to mental health following debrief. CONCLUSIONS: Without the need for additional resources, implementation of the MY-Q in a pediatric tertiary care diabetes clinic successfully identified QoL issues and mental health concerns among adolescents with T1D.

Normative values of renin and aldosterone in clinically stable preterm neonates.

BACKGROUND: There is a paucity of literature on the normative levels of plasma renin concentration (PRC) and serum aldosterone (SA) in premature neonates. This study aims to provide normative data on PRC and SA levels in preterm neonates in the first 2 weeks after birth and explore associations with maternal, perinatal, or postnatal factors. METHODS: Neonates born at 26- to 34-week gestation were recruited from two neonatal intensive care units in Canada and Australia. The direct renin assay PRC and SA were analyzed on day 1 and days 14-21 after birth to compare across categorical variables and to produce normative values. RESULTS: A total of 262 subjects were enrolled from the Canadian (29%) and Australian (71%) sites. The mean gestational age was 30 weeks, with a mean birth weight of 1457 g. The normative values of PRC and SA for neonates born between 26 + 0 and 29 + 6 weeks and 30 + 0 and 34 + 0 weeks of gestation were produced for day 1 and day 14-21 after birth. Both PRC and SA increased from day 1 to day 14-21. The more premature neonates reached a higher PRC on days 14-21 after birth but exhibited lower SA levels on day 1 after birth. When comparing gender, birth weight, and maternal risk factor categories, no statistical differences in PRC or SA were found. A small but significant decrease in PRC, but not SA, was noted for neonates with placental pathology. CONCLUSIONS: This study produced normative values of PRA and SA in clinically stable preterm neonates that can be referenced for use in clinical practice. A higher resolution version of the Graphical abstract is available as Supplementary information.

Frequency of Unscheduled Visits to the Obstetrical Triage Assessment Unit by Pregnant Adolescents in an Urban Canadian Centre Compared with a Matched Cohort of Pregnant Women.

OBJECTIVES: People from marginalized and vulnerable populations present more frequently for unscheduled, emergency obstetrical services at labour and delivery triage units. Based on our clinical experience, pregnant adolescents visit the obstetrical triage assessment units (OTAU) more often than adults do. This study was designed to assess this phenomenon by quantifying and describing the frequency of unscheduled visits to the OTAU by pregnant adolescents (age <20 y) compared with a matched cohort of adult pregnant patients (age ≥20 y). METHODS: A retrospective database review was performed for data on all adolescent patients that delivered at our institution at ≥20 weeks gestation between January 1, 2013, and December 31, 2017. Adolescent pregnant patients were matched in a 1:1 ratio with adult pregnant patients. Demographic and clinical characteristics as well as the number of visits to the OTAU were recorded. RESULTS: A total of 162 adolescent pregnant patients visited the OTAU during the study period. The mean number of visits to the OTAU by adolescents was 2.77 ± 2.40 compared with 1.96 ± 1.80 visits in the adult cohort (P = 0.0001). Adolescents were 63% more likely than adults to access triage services (incidence rate ratio [IRR] 1.63; 95% CI 1.09-2.44, P = 0.017). Diagnosis of a mental health condition was the only identified risk factor for accessing OTAU, irrespective of age (IRR 1.64; 95% CI 1.05, 2.55, P = 0.029). CONCLUSIONS: Adolescent pregnant patients tend to visit the OTAU on an unscheduled basis more often than do adult patients. The presence of a mental health condition was identified as an important predictor of unscheduled visits to OTAUs for adolescent patients.

Combined influence of practice guidelines and prospective audit and feedback stewardship on antimicrobial treatment of community-acquired pneumonia and empyema in children: 2012 to 2016.

BACKGROUND: Aminopenicillins are recommended empiric therapy for community-acquired pneumonia (CAP). The aim of the study was to assess treatment over a 5-year period after CAP guideline publication and introduction of an antimicrobial stewardship program (ASP). METHODS: Using ICD-10 discharge codes for pneumonia, children less than 18 years admitted to the Children's Hospital of Eastern Ontario January 1, 2012 and December 31, 2016 were identified. Children ≥ 2 months with consolidation were included. One day of therapy (DOT) was one or more doses of an antimicrobial given for 1 day. RESULTS: Of 1,707 patients identified, 713 met inclusion criteria. Eighteen (2.5%) had bacteria identified by culture and 79 of 265 (29.8%) had Mycoplasma pneumoniae detected. Mean DOT/1,000 patient days of aminopenicillins/penicillin (AAP) increased by 18.1% per year (95% confidence interval [CI] -0.2, 39.9%) and decreased by 37.6% per year (95% CI -56.1, -11.3%) for second- and third-generation cephalosporins in the post-ASP period. The duration of discharge antimicrobials decreased. Of 74 (10.4%) patients who had pleural fluid drained, 35 (47.3%) received more than 5 days of AAP and ≤ 5 days of second-/third-generation cephalosporins with no difference in median length of stay nor mean duration of antimicrobials. CONCLUSIONS: Implementation of CAP management guidelines followed by prospective audit and feedback stewardship was associated with a sustained decrease in the use of broad-spectrum antibiotics in childhood CAP. Use of AAP should also be strongly considered in patients with effusions (even if no pathogen is identified), as clinical outcome appears similar to patients treated with broad-spectrum antimicrobials.

Validating the Implementation Leadership Scale in Chinese nursing context: A cross-sectional study.

AIM: This study aimed to evaluate the validity, reliability and acceptability of the Implementation Leadership Scale in the Chinese nursing context. DESIGN: This study utilized a cross-sectional design. METHODS: This study was conducted in one general tertiary hospital with 234 nurses (85.3% response rate) from 35 clinical units in China. Content validity, structural validity, convergent validity, reliability (internal consistency), agreement indices and acceptability were evaluated. The data collection was from December 1st, 2017 to June 30th, 2018. RESULTS: Confirmatory factor analysis demonstrated a good model fit to the four-factor implementation leadership model. The psychometric testing also indicated good convergent validity, high internal consistency and acceptable aggregation. Most participants completed the scale in two minutes or less and agreed or strongly agreed that the questions were relevant to implementation leadership, clear and easy to answer. CONCLUSIONS: This study demonstrated that the Chinese Implementation Leadership Scale is a valid, reliable and pragmatic tool for measuring strategic leadership for implementing evidence-based practices.

Factors related to positive airway pressure therapy adherence in children with obesity and sleep-disordered breathing.

STUDY OBJECTIVES: Positive airway pressure (PAP) is used to treat children with concurrent obesity and sleep-disordered breathing (SDB), but achieving adherence remains challenging. We aimed to identify factors associated with PAP adherence in a prospective cohort of children with obesity prescribed PAP for newly diagnosed SDB. METHODS: A questionnaire to assess factors related to PAP adherence was administered to participants and their parent ≥12 months after enrollment. Adherence (PAP use ≥4 hours/night on >50% of nights) was measured with PAP machine downloads, diaries, and physician assessments. Questionnaire responses were compared between adherent/nonadherent participants and between children/parents. Age, total and obstructive apnea-hypopnea index (OAHI), lowest oxygen saturation, and highest carbon dioxide were compared between adherent/nonadherent children with univariate differences of medians, with 95% confidence intervals. RESULTS: Fourteen children (median age: 14.3 years; 93% male; all with obstructive sleep apnea) were included. Eleven (79%) were adherent to PAP. SDB symptom improvement was reported in 9 of 14 children (64%); 8 of 14 children (57%) had positive experiences with PAP. Most children assumed an active role in PAP initiation and felt supported by the clinical team. Responses between adherent/nonadherent groups and between children/parents were similar. Oxygen saturation nadir (median difference between nonadherent and adherent groups: 8.9%; 95% confidence interval: 1.7, 16.1), but not age, apnea-hypopnea index, OAHI, or maximum carbon dioxide, was associated with PAP adherence. CONCLUSIONS: Children with obesity-related SDB with lower nocturnal oxygen saturation nadir were more likely to adhere to PAP therapy. Ensuring adequate understanding of PAP therapy and medical team support are key factors in PAP success.

Practice variation in the management of children hospitalized with bronchiolitis: A Canadian perspective.

OBJECTIVES: To describe variations in the monitoring, treatment, and discharge of children hospitalized with bronchiolitis among physicians across Canadian paediatric teaching hospitals. METHODS: We conducted an electronic survey of paediatricians with experience in the management of inpatient bronchiolitis at 20 Canadian paediatric teaching hospitals. Only physicians who worked a minimum of 6 weeks on their hospital inpatient unit in the 2015 calendar year were eligible to participate in the study. The questionnaire explored the monitoring, treatment, and discharge of children with bronchiolitis. Central tendency (mean) and dispersion (SD) statistics were produced for continuous variables and frequency distributions for categorical variables. RESULTS: A total of 142 respondents were included in the analysis. 45.1% reported the routine use of continuous oxygen saturation monitoring. 27.5% used a higher cut-off for oxygen supplementation of 92% and 12.7% use a lower cut-off of 88%. 29.6% routinely used deep nasal suctioning. Seventy-three per cent reported using nebulized therapies. 55.6% reported having preprinted order sheets or guidelines for management of inpatient bronchiolitis at their institutions and 28.2% reported having specific discharge criteria. The length of time required to be off oxygen prior to discharge varied (31% at 12 hours, 27.5% at 24 hours, and 24.6% after the last sleep period without oxygen). CONCLUSION: There is significant practice variation in the monitoring, treatment, and discharge of children hospitalized with bronchiolitis within and between Canadian paediatric teaching hospitals. Future research is needed to establish best practices, effective knowledge translation, and implementation strategies to standardize care and decrease length of stay.

Contemporary Microbiology and Antimicrobial Treatment of Complicated Appendicitis: The Value of a Short-term Study.

BACKGROUND: Antimicrobial stewardship interventions to curtail the use of third-generation cephalosporins and antipseudomonal penicillins for the treatment of complicated appendicitis in children are challenging given the tendency to treat complicated disease with broad-spectrum antimicrobials. Reasons for this are unclear, but there is a paucity of contemporary microbiologic data associated with the child presenting with either acute perforated or gangrenous appendicitis. This study aimed to justify the appropriateness of an empiric regimen consisting of ampicillin, tobramycin/gentamicin plus metronidazole and to analyze duration of postoperative therapy. METHODS: We conducted a retrospective cohort study from February 1, 2017, to October 31, 2018, in children who underwent appendectomy or interventional radiologic drainage for primary complicated appendicitis. The primary outcome was the proportion of patients who had a pathogen isolated from peritoneal fluid culture that was not susceptible to the recommended empiric therapy. The secondary outcomes were the total duration of antimicrobial therapy and the proportion of patients with a postoperative infectious complication within 30 days after intervention. RESULTS: Of 425 children with primary acute appendicitis, 158 (37%) had complicated appendicitis at presentation. Culture was performed in 53 (40%) of the 133 who underwent a surgical or interventional radiologic intervention. The group with peritoneal cultures was more likely to present with longer symptom duration before admission [3 (interquartile range, 2-5) vs 2 (interquartile range, 1-2) days; P < 0.001] and with purulent peritonitis [47% (25/53) vs 13% (10/80); P < 0.001]. The most common pathogens isolated were anaerobes (81%), Escherichia coli (74%) and Streptococcus anginosus group (62%). Only 4% of isolated bacteria were resistant to empiric therapy. Postoperative infectious complications were documented in 23 (17%) patients and were not associated with the presence of a resistant pathogen or the choice of antimicrobial agents but with more severe disease and higher C-reactive protein values (303 vs 83 mg/L; P=0.03) at presentation. CONCLUSIONS: In a cohort of previously healthy children presenting with complicated appendicitis requiring surgical drainage, the most common bacteria from peritoneal cultures continue to be S. anginosus, aminoglycoside-susceptible Gram-negative bacilli and anaerobes. In an attempt to reduce extended-spectrum cephalosporin use, these data were useful in supporting the use of metronidazole with ampicillin and an aminoglycoside, rather than third-generation cephalosporins.

Influence of timing of initiation of therapeutic hypothermia on brain MRI and neurodevelopment at 18 months in infants with HIE: a retrospective cohort study.

OBJECTIVE: To examine the influence of timing of initiation of therapeutic hypothermia (TH) on brain injury on MRI and on neurodevelopmental outcomes at 18 months. DESIGN: Retrospective cohort study. SETTING: Tertiary neonatal intensive care unit in Ontario, Canada. PATIENTS: Ninety-one patients with hypoxic ischaemic encephalopathy (HIE) were included, 54 in the early TH group and 37 in the late TH group. INTERVENTION: Whole-body hypothermia administered for 72 hours, initiated either before 3 hours of life (early TH) or between 3 and 6 hours of life (late TH). MAIN OUTCOME MEASURES: Brain injury on MRI after TH (assessed by two neuroradiologists), and neurodevelopmental outcomes at 18 months old. RESULTS: TH was initiated at a median time of 1.4 hours (early TH) and 4.4 hours (late TH). Sixty-four neonates (early TH=36, late TH=28) survived and completed neurodevelopmental assessment at 18 months. Neonates in the early TH group received more extensive resuscitation than neonates in the late TH group (p=0.0008). No difference was observed between the two groups in the pattern or severity of brain injury on MRI, or in the neurodevelopmental outcomes at 18 months. The non-survivors (n=16) had lower Apgar scores at 10 min, more extensive resuscitation, suffered from more severe HIE and had significantly more abnormal cerebral function monitoring. CONCLUSION: In this retrospective cohort study, TH initiated early was associated neither with a difference in brain injury on MRI nor better neurodevelopmental outcomes at 18 months.

Factors Impacting Physician Recommendation for Tracheostomy Placement in Pediatric Prolonged Mechanical Ventilation: A Cross-Sectional Survey on Stated Practice.

OBJECTIVES: To characterize the stated practices of qualified Canadian physicians toward tracheostomy for pediatric prolonged mechanical ventilation and whether subspecialty and comorbid conditions impact attitudes toward tracheostomy. DESIGN: Cross sectional web-based survey. SUBJECTS: Pediatric intensivists, neonatologists, respirologists, and otolaryngology-head and neck surgeons practicing at 16 tertiary academic Canadian pediatric hospitals. INTERVENTIONS: Respondents answered a survey based on three cases (Case 1: neonate with bronchopulmonary dysplasia; Cases 2 and 3: children 1 and 10 years old with pediatric acute respiratory distress syndrome, respectively) including a series of alterations in relevant clinical variables. MEASUREMENTS AND MAIN RESULTS: We compared respondents' likelihood of recommending tracheostomy at 3 weeks of mechanical ventilation and evaluated the effects of various clinical changes on physician willingness to recommend tracheostomy and their impact on preferred timing (≤ 3 wk or > 3 wk of mechanical ventilation). Response rate was 165 of 396 (42%). Of those respondents who indicated they had the expertise, 47 of 121 (38.8%), 23 of 93 (24.7%), and 40 of 87 (46.0%) would recommend tracheostomy at less than or equal to 3 weeks of mechanical ventilation for cases 1, 2, and 3, respectively (p < 0.05 Case 2 vs 3). Upper airway obstruction was associated with increased willingness to recommend earlier tracheostomy. Life-limiting condition, severe neurologic injury, unrepaired congenital heart disease, multiple organ system failure, and noninvasive ventilation were associated with a decreased willingness to recommend tracheostomy. CONCLUSION: This survey provides insight in to the stated practice patterns of Canadian physicians who care for children requiring prolonged mechanical ventilation. Physicians remain reluctant to recommend tracheostomy for children requiring prolonged mechanical ventilation due to lung disease alone at 3 weeks of mechanical ventilation. Prospective studies characterizing actual physician practice toward tracheostomy for pediatric prolonged mechanical ventilation and evaluating the impact of tracheostomy timing on clinically important outcomes are needed as the next step toward harmonizing care delivery for such patients.

Effect of anesthesia for hypospadias repair on perioperative complications.

BACKGROUND: Recent publications from the United States, India, and Korea report that children undergoing hypospadias repair with caudal regional anesthesia/analgesia could have increased postoperative surgical complications. AIMS: The purpose of this retrospective cohort study was to assess the impact between caudal regional anesthesia, other regional anesthesia, and no regional anesthesia on complications after hypospadias repair at a tertiary care children's hospital in Ottawa, Canada, with an expectation to changing practices if a link was found. METHOD: We reviewed the health records of 827 children with hypospadias undergoing penile surgery from January 1991-June 2017. The final sample size for the analysis consisted of 764 patients and 825 procedures. RESULTS: The overall complications were almost identical when considering anesthesia effects, and this similarity persisted when we assessed specifically for only surgical complications. We had 716, 94, and 15 subjects who had a caudal block, penile block, and general anesthesia only, respectively, and their complication rates were 28, 31, and 27%, respectively, and their fistula formation rates were 10, 6, and 0%, respectively, and their stricture formation rates were 8, 7, and 20%,, respectively. Hypospadias type and surgical repair technique were marked predictors of complications in the postoperative period. CONCLUSION: Anesthesia technique appears to have minor impact on complications after hypospadias repair, while surgical technique and type of hypospadias impact complications after hypospadias surgery in children. Based upon these results, we will not change our current practice of using a variety of regional anesthesia techniques for children undergoing hypospadias repair.

Scaling of noisy fluctuations in complex networks and applications to network prediction.

We study the collective dynamics of oscillator-network systems in the presence of noise. By focusing on the time-averaged fluctuation of dynamical variable of interest about the mean field, we discover a scaling law relating the average fluctuation to the node degree. The scaling law is quite robust as it holds for a variety of network topologies and node dynamics. Analyses and numerical support for different types of networks and node dynamics are provided. We also point out an immediate application of the scaling law: predicting complex networks based on time series only, and we articulate how this can be done.

Detection of seizure rhythmicity by recurrences.

Epileptic seizures show a certain degree of rhythmicity, a feature of heuristic and practical interest. In this paper, we introduce a simple model of this type of behavior, and suggest a measure for detecting and quantifying it. To evaluate our method, we develop a set of test segments that incorporate rhythmicity features, and present results from the application of this measure to test segments. We then analyze electrocorticogram segments containing seizures, and present two examples. Finally, we discuss the similarity of our method to techniques for detecting unstable periodic orbits in chaotic time series.

Correlation dimension and integral do not predict epileptic seizures.

Reports in the literature have indicated potential value of the correlation integral and dimension for prediction of epileptic seizures up to several minutes before electrographic onset. We apply these measures to over 2000 total hours of continuous electrocortiogram, taken from 20 patients with epilepsy, examine their sensitivity to quantifiable properties such as the signal amplitude and autocorrelation, and investigate the influence of embedding and filtering strategies on their performance. The results are compared against those obtained from surrogate time series. Our conclusion is that neither the correlation dimension nor the correlation integral has predictive power for seizures.

Accumulated energy revisited.

OBJECTIVE: To examine the seizure prediction and detection abilities of the accumulated energy on multi-center data submitted to the First International Collaborative Workshop on Seizure Prediction. METHODS: The accumulated energy (AE), windowed average power, and FHS seizure detection algorithm were applied to a single channel of ECoG data taken from the data sets contributed to the workshop. The FHS seizure detection algorithm was used to perform automated scoring of the data in order to locate subclinical events not picked up by the centers where the data was collected. The results were analyzed retrospectively, comparing the behavior of the accumulated energy and windowed average power on segments containing seizures to interictal segments. RESULTS: Accumulated energy curves showed no divergence from interictal curves prior to seizure. Distinctive or clear increases in the AE slope occurred sometime at or after electrographic seizure onset for some seizures. Similarly, the windowed average power showed no consistent increases in broadband energy prior to seizures. However, both methods may have detection ability for some seizures. CONCLUSIONS: The accumulated energy did not appear to have predictive abilities for these data sets. Some detection ability was apparent. SIGNIFICANCE: In data unsorted by sleep/wake state, no seizure prediction was evident. The lack of prediction calls into question the existence of a preictal state as previously claimed in the literature using this method.

Controlled test for predictive power of Lyapunov exponents: their inability to predict epileptic seizures.

Lyapunov exponents are a set of fundamental dynamical invariants characterizing a system's sensitive dependence on initial conditions. For more than a decade, it has been claimed that the exponents computed from electroencephalogram (EEG) or electrocorticogram (ECoG) signals can be used for prediction of epileptic seizures minutes or even tens of minutes in advance. The purpose of this paper is to examine the predictive power of Lyapunov exponents. Three approaches are employed. (1) We present qualitative arguments suggesting that the Lyapunov exponents generally are not useful for seizure prediction. (2) We construct a two-dimensional, nonstationary chaotic map with a parameter slowly varying in a range containing a crisis, and test whether this critical event can be predicted by monitoring the evolution of finite-time Lyapunov exponents. This can thus be regarded as a "control test" for the claimed predictive power of the exponents for seizure. We find that two major obstacles arise in this application: statistical fluctuations of the Lyapunov exponents due to finite time computation and noise from the time series. We show that increasing the amount of data in a moving window will not improve the exponents' detective power for characteristic system changes, and that the presence of small noise can ruin completely the predictive power of the exponents. (3) We report negative results obtained from ECoG signals recorded from patients with epilepsy. All these indicate firmly that, the use of Lyapunov exponents for seizure prediction is practically impossible as the brain dynamical system generating the ECoG signals is more complicated than low-dimensional chaotic systems, and is noisy.

Stimulation of calcineurin signaling attenuates the dystrophic pathology in mdx mice.

Utrophin has been studied extensively in recent years in an effort to find a cure for Duchenne muscular dystrophy. In this context, we previously showed that mice expressing enhanced muscle calcineurin activity (CnA*) displayed elevated levels of utrophin around their sarcolemma. In the present study, we therefore crossed CnA* mice with mdx mice to determine the suitability of elevating calcineurin activity in preventing the dystrophic pathology. Muscles from mdx/CnA* displayed increased nuclear localization of NFATc1 and a fiber type shift towards a slower phenotype. Measurements of utrophin levels in mdx/CnA* muscles revealed an approximately 2-fold induction in utrophin expression. Consistent with this induction, we also observed that members of the dystrophin-associated protein (DAP) complex were present at the sarcolemma of mdx/CnA* mouse muscle. This restoration of the utrophin-DAP complex was accompanied by significant reductions in the extent of central nucleation and fiber size variability. Importantly, assessment of myofiber sarcolemmal damage, as monitored by the intracellular presence of IgM and albumin as well as by Evans blue uptake in vivo, revealed a net amelioration of membrane integrity. Finally, immunofluorescence experiments using Mac-1 antibodies showed a reduction in the number of infiltrating immune cells in muscles from mdx/CnA* mice. These results show that elevated calcineurin activity attenuates the dystrophic pathology and thus provides an effective target for pharmacological intervention.

Inability of Lyapunov exponents to predict epileptic seizures.

It has been claimed that Lyapunov exponents computed from electroencephalogram or electrocorticogram (ECoG) time series are useful for early prediction of epileptic seizures. We show, by utilizing a paradigmatic chaotic system, that there are two major obstacles that can fundamentally hinder the predictive power of Lyapunov exponents computed from time series: finite-time statistical fluctuations and noise. A case study with an ECoG signal recorded from a patient with epilepsy is presented.

Expression of utrophin A mRNA correlates with the oxidative capacity of skeletal muscle fiber types and is regulated by calcineurin/NFAT signaling.

Utrophin levels have recently been shown to be more abundant in slow vs. fast muscles, but the nature of the molecular events underlying this difference remains to be fully elucidated. Here, we determined whether this difference is due to the expression of utrophin A or B, and examined whether transcriptional regulatory mechanisms are also involved. Immunofluorescence experiments revealed that slower fibers contain significantly more utrophin A in extrasynaptic regions as compared with fast fibers. Single-fiber RT-PCR analysis demonstrated that expression of utrophin A transcripts correlates with the oxidative capacity of muscle fibers, with cells expressing myosin heavy chain I and IIa demonstrating the highest levels. Functional muscle overload, which stimulates expression of a slower, more oxidative phenotype, induced a significant increase in utrophin A mRNA levels. Because calcineurin has been implicated in controlling this slower, high oxidative myofiber program, we examined expression of utrophin A transcripts in muscles having altered calcineurin activity. Calcineurin inhibition resulted in an 80% decrease in utrophin A mRNA levels. Conversely, muscles from transgenic mice expressing an active form of calcineurin displayed higher levels of utrophin A transcripts. Electrophoretic mobility shift and supershift assays revealed the presence of a nuclear factor of activated T cells (NFAT) binding site in the utrophin A promoter. Transfection and direct gene transfer studies showed that active forms of calcineurin or nuclear NFATc1 transactivate the utrophin A promoter. Together, these results indicate that expression of utrophin A is related to the oxidative capacity of muscle fibers, and implicate calcineurin and its effector NFAT in this mechanism.

Correlation-dimension and autocorrelation fluctuations in epileptic seizure dynamics.

We focus on an anomalous scaling region in correlation integral [C(epsilon)] analysis of electrocorticogram in epilepsy patients. We find that epileptic seizures typically are accompanied by wide fluctuations in the slope of this scaling region. An explanation, based on analyzing the interplay between the autocorrelation and C(epsilon), is provided for these fluctuations. This anomalous slope appears to be a sensitive measure for tracking (but not predicting) seizures.