Left ventricular non-compaction in children and adolescents: Clinical features, treatment and follow-up

Background: Left ventricular non-compaction (LVNC) is a specific cardiomyopathy that occurs following a disruption of endomyocardial morphogenesis. This study presents clinical findings, diagnostic features, treatment and follow-up of pediatric patients diagnosed with LVNC. Methods: Patients with LVNC who were followed from January 2006 to March 2010 were included in this study. Diagnosis was made with the use of characteristic findings of magnetic resonance imaging and echocardiography. Holter electrocardiography and metabolic screening tests were also performed in all patients. Results: A total of 24 patients were studied (18 male, six female). Patient age at diagnosis was 50 ± 60 months (eight days to 15 years). Average follow-up period was 22 ± 12 months (four months to four years). Findings at diagnosis were as follows: eight (33%) patients had heart failure, five (20%) had rhythm abnormalities, five (20%) had cardiomegaly, two had murmurs, two had cyanosis, and two presented with fatigue. Ten (41%) patients had been followed previously with other diagnoses. In 21 (87.5%) patients, electrocardiographic abnormalities were noted, especially left ventricular hypertrophy and ST-T changes. Patients had an average ejection fraction of 46% (18-73%) and three of them had additional congenital heart disease (patent ductus arteriosus, aortopulmonary window and complex cyanotic heart disease). Scanning for metabolic diseases revealed fatty acid oxidation disorder in one patient, and mitochondrial disease in another. During follow-up, a permanent pacemaker was implanted in a patient with severe bradycardia and ventricular dysfunction, and three patients died. Conclusion: LVNC can be diagnosed at any age from newborn to adolescent and has a variable clinical course. Closer study of patients with cardiomegaly and heart failure can reduce delays in diagnosis of LVNC. (Cardiol J 2011; 18, 2: 176-184

Prevention of conversion to abnormal tcd with hydroxyurea in sickle cell anemia: A phase III international randomized clinical trial

Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170-199 cm/sec) may develop stroke. However, with limited available clinical data, the current standard of care for conditional TCD velocities is observation. The efficacy of hydroxyurea in preventing conversion from conditional to abnormal TCD (\u3e/=200 cm/sec), which confers a higher stroke risk, has not been studied prospectively in a randomized trial. Sparing Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was an NHLBI-funded Phase III multicenter international clinical trial comparing alternative therapy (hydroxyurea) to standard care (observation) to prevent conversion from conditional to abnormal TCD velocity in children with SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS (36), HbSbeta0 -thalassemia (1), and HbSD (1), median age 5.4 years (range, 2.7-9.8)]. Due to slow patient accrual and administrative delays, SCATE was terminated early. In an intention-to-treat analysis, the cumulative incidence of abnormal conversion was 9% (95% CI 0 to 35%) in the hydroxyurea arm and 47% (95% CI 6 to 81%) in observation arm at 15 months (p=0.16). In post-hoc analysis according to treatment received, significantly fewer children on hydroxyurea converted to abnormal TCD velocities, compared to observation (0% versus 50%, p=0.02). After a mean of 10.1 months, a significant change in mean TCD velocity was observed with hydroxyurea treatment (-15.5 versus +10.2 cm/sec, p=0.02). No stroke events occurred in either arm. Hydroxyurea reduces TCD velocities in children with SCA and conditional velocities. This article is protected by copyright. All rights reserved

Live Cell Imaging of Bone Marrow Stromal Cells on Nano-pitted and Polished Titanium Surfaces: A Micro-Incubator in vitro Approach

Current orthopedic implants are not conducive for optimal integration of the biomaterial with newly-formed tissue (osseointegration) inside a patient’s body. In this study, medical-rade Ti-6Al-4V was used as a substrate due to its biocompatibility and ability to facilitate cellular adhesion and proliferation. Live cell imaging was conducted on bone marrow stromal cells, genetically modified to express the green fluorescent protein (GFP), from the 24-96 hours growth period, with the first 24 hours of growth being held inside a lab-scale incubator. Periodic images were recorded on nanopitted anodized and polished Ti-6Al-4V substrates to study how substratestiffness influences adhesion and proliferation. Collected images were analyzed for mitosis, adhesion, and filopodia-stretchability using ImageJ, an image processing program. Images were enhanced in order to perform cell counts at 24, 48, 72, and 96 hours of growth. Continuous recordings were produced to account for the number of mitosis occurrences and cellular migration on each of the substrates. Based on the conducted experiments, it appears that polished Ti-6Al-4V has a higher cell adherence than “nanopitted” anodized surface and an improved rate of proliferation which may be because the cells once adhered on the nano-pitted surface have less ability to detach in-order to undergo mitosis.https://engagedscholarship.csuohio.edu/u_poster_2014/1004/thumbnail.jp

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

AbstractDevelopmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy.</jats:p

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

International nosocomial infection control consortium (INICC) report, data summary of 36 countries, for 2004-2009

The results of a surveillance study conducted by the International Nosocomial Infection Control Consortium (INICC) from January 2004 through December 2009 in 422 intensive care units (ICUs) of 36 countries in Latin America, Asia, Africa, and Europe are reported. During the 6-year study period, using Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN; formerly the National Nosocomial Infection Surveillance system [NNIS]) definitions for device-associated health care-associated infections, we gathered prospective data from 313,008 patients hospitalized in the consortium's ICUs for an aggregate of 2,194,897 ICU bed-days. Despite the fact that the use of devices in the developing countries' ICUs was remarkably similar to that reported in US ICUs in the CDC's NHSN, rates of device-associated nosocomial infection were significantly higher in the ICUs of the INICC hospitals; the pooled rate of central line-associated bloodstream infection in the INICC ICUs of 6.8 per 1,000 central line-days was more than 3-fold higher than the 2.0 per 1,000 central line-days reported in comparable US ICUs. The overall rate of ventilator-associated pneumonia also was far higher (15.8 vs 3.3 per 1,000 ventilator-days), as was the rate of catheter-associated urinary tract infection (6.3 vs. 3.3 per 1,000 catheter-days). Notably, the frequencies of resistance of Pseudomonas aeruginosa isolates to imipenem (47.2% vs 23.0%), Klebsiella pneumoniae isolates to ceftazidime (76.3% vs 27.1%), Escherichia coli isolates to ceftazidime (66.7% vs 8.1%), Staphylococcus aureus isolates to methicillin (84.4% vs 56.8%), were also higher in the consortium's ICUs, and the crude unadjusted excess mortalities of device-related infections ranged from 7.3% (for catheter-associated urinary tract infection) to 15.2% (for ventilator-associated pneumonia). Copyright © 2012 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved

Effects of Species-Specific Auditory Stimulation on Broiler Embryos on Hatchability, Developmental Stability, Behavior, and Performance Characteristics

The aim of this study is to expose broiler embryos to species-specific sounds from the 444th and 468th hours of incubation until the end of incubation and, thus, to determine the effects of these stimulations on their hatching characteristics, performance traits, developmental stability, and behavioral characteristics. Auditory stimulation sounds are a total of 5 min of recording consisting of sounds made by embryos during and after internal piping and response sounds made by the broody hen at that time. The auditory stimulation pattern was created as 5 min of recording and 5 min of silence for a total of 20 min of recording, and this sound pattern was played continuously with 65 dB sound intensity and 800 Hz sound frequency. A total of 750 Ross 308 broiler hatching eggs were equally divided into three groups (AS1: auditory stimulation from hour 444, AS2: sound stimulation from hour 468), and two stimulation groups and a control (silent) group were incubated in three homologous incubators. Due to auditory stimulation, the hatching window in embryos exposed to species-specific sounds beginning at the 444th hour of the incubation period was determined to be 28 h in this study. Auditory stimulation was late in the embryos exposed to species-specific sounds from the 468th hour of incubation, and the incubation windows in this group and the silent (control) group were determined to be 36 h and 40 h, respectively. The chicks that were exposed to early auditory stimulation during incubation exhibited a higher average Tona score (99.03) in comparison to the other groups (p p < 0.05). Auditory stimulation during incubation had no effect on live weight, Gompertz growth curve parameters, feed conversion ratio, slaughter-carcass characteristics, behavioral traits, or developmental balance characteristics. Consequently, it was determined that the incubation window and the number of marketable chicks were both substantially impacted by the implementation of species-specific auditory stimulation. However, further research is required to ascertain the precise timing of this auditory stimulation

Evaluation of Pediatric Patients with First Seizure

Objective: Pediatric seizure is a condition that occurs due to many different underlying causes and causes fear and anxiety in families. In our study, it was aimed to evaluate pediatric seizure cases who applied to our hospital. Methods: Patients aged 0-18 years, who applied to the pediatric emergency department of our hospital between May 2018 and May 2020, were retrospectively analyzed. The patients were evaluated in terms of age, gender, seizure types, familial genetic predisposition, examination, treatment and follow-up. Seizures were divided into 2 groups as focal and generalized according to the International League Against Epilepsy (ILAE) 2017 classification. The treatment methods applied with cranial magnetic resonance imaging and electroencephalography recordings of the patients were evaluated. Results: Of the 118 patients included in the study, 70 (59 %) were girls and 48 (41 %) were boys. The mean age was 60 (3-192) months. Family history was present in 18 (15 %) cases. 8 (7 %) of the seizures are partial and 110 (93 %) of them are generalized. Since seizure recurrence was observed within 24 hours in 5 of 36 patients who were evaluated as febrile seizures, they were evaluated as complicated febrile seizures and drug treatment was started. The other 31 patients were evaluated as simple febrile seizures. There was no biochemical abnormality in the seizure etiology in any of the cases. Cranial magnetic resonance imaging revealed polymicrogyria in 2 patients, hydrocephalus in 2 patients, brain tumor in 1 patient, and arteriovenous malformation in 1 patient. Conclusions: In cases presenting with seizures, the underlying causes should be identified and their treatment should be arranged. Cases with recurrent seizures should also be followed closely