Showing papers by "Atlantic Health System published in 2017"

Orexin System: The Key for a Healthy Life

Abstract: The orexin-A/hypocretin-1 and orexin-B/hypocretin-2 are neuropeptides synthesized by a cluster of neurons in the lateral hypothalamus and perifornical area Orexin neurons receive a variety of signals related to environmental, physiological and emotional stimuli, and project broadly to the entire CNS Orexin neurons are “multi-tasking” neurons regulating a set of vital body functions, including sleep/wake states, feeding behaviour, energy homeostasis, reward systems, cognition and mood Furthermore, a dysfunction of orexinergic system may underlie different pathological conditions The selective loss orexin neurons was found in narcolepsia, supporting the crucial role of orexins in maintaining wakefulness In animal models, orexin deficiency lead to obesity even if the consume of calories is lower than wildtype counterpart Reduced physical activity appears the main cause of weight gain in these models resulting in energy imbalance Interestingly, orexinergic neurons show connections to regions involved in cognition and mood regulation, including hippocampus Orexins enhance hippocampal neurogenesis and improve spatial learning and memory abilities, and mood Conversely, orexin deficiency results in learning and memory deficits, and depression

The lysosomal protein cathepsin L is a progranulin protease.

Abstract: Haploinsufficiency of GRN, the gene encoding progranulin (PGRN), causes frontotemporal lobar degeneration (FTLD), the second most common cause of early-onset dementia. Receptor-mediated lysosomal targeting has been shown to regulate brain PGRN levels, and complete deficiency of PGRN is a direct cause of neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. Here we show that the lysosomal cysteine protease cathepsin L (Cat L) can mediate the proteolytic cleavage of intracellular PGRN into poly-granulin and granulin fragments. Further, PGRN and Cat L co-localize in lysosomes of HEK293 cells, iPSC-derived neurons and human cortical neurons from human postmortem tissue. These data identify Cat L as a key intracellular lysosomal PGRN protease, and provides an intriguing new link between lysosomal dysfunction and FTLD.

Early provision of oropharyngeal colostrum leads to sustained breast milk feedings in preterm infants

Abstract: Background Oropharyngeal colostrum (OC) application strategies have been shown to be feasible and safe for very low birth weight (VLBW) infants. Evidence to support the nutritional and clinical advantages of OC care remains somewhat theoretical. The objectives of this study were to a) confirm the feasibility and safety of OC application in preterm infants and b) determine if OC application is associated with improved nutritional and clinical outcomes from birth to discharge. We hypothesized that OC application in the first few days would promote sustained breast milk feedings through discharge. Methods An observational longitudinal study was conducted in 133 VLBW infants during 2013–14, after an OC protocol was adopted. Maternal and infant characteristics, infant vital signs during administration, nutritional outcomes, and common neonatal morbidities were assessed and compared to 85 age- and weight-matched VLBW infants from a retrospective control cohort from 2012, prior to the implementation of the OC protocol. Results There were no adverse events or changes in vital signs during the application of OC. VLBW infants who received OC continued to receive the majority of their enteral feeds from human breast milk at six 6 of age and through discharge ( p Conclusion OC application for VLBW infants is safe and practical in a neonatal intensive care unit setting and is associated with increased rates of breast milk feeding.

Mouse Models of C9orf72 Hexanucleotide Repeat Expansion in Amyotrophic Lateral Sclerosis/ Frontotemporal Dementia.

Abstract: The presence of hexanucleotide repeat expansion (HRE) in the first intron of the human C9orf72 gene is the most common genetic cause underlying both familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Studies aimed at elucidating the pathogenic mechanisms associated of C9orf72 FTD and ALS (C9FTD/ALS) have focused on the hypothesis of RNA and protein toxic gain-of-function models, including formation of nuclear RNA foci containing GGGGCC (G4C2) HRE, inclusions containing dipeptide repeat proteins through a non-canonical repeat associated non-ATG (RAN) translation mechanism, and on loss-of-function of the C9orf72 protein. Immense effort to elucidate these mechanisms has been put forth and toxic gain-of-function models have especially gained attention. Various mouse models that recapitulate distinct disease-related pathological, functional, and behavioral phenotypes have been generated and characterized. Although these models express the C9orf72 HRE mutation, there are numerous differences among them, including the transgenesis approach to introduce G4C2-repeat DNA, genomic coverage of C9orf72 features in the transgene, G4C2-repeat length after genomic stabilization, spatiotemporal expression profiles of RNA foci and RAN protein aggregates, neuropathological features, and neurodegeneration-related clinical symptoms. This review aims to (1) provide an overview of the key characteristics; (2) provide insights into potential pathological factors contributing to neurotoxicity and clinical phenotypes through systematic comparison of these models.

The Use of a Computerized Provider Order Entry Alert to Decrease Rates of Clostridium difficile Testing in Young Pediatric Patients.

Abstract: BACKGROUND Infants and young children are frequently colonized with C. difficile but rarely have symptomatic disease. However, C. difficile testing remains prevalent in this age group. OBJECTIVE To design a computerized provider order entry (CPOE) alert to decrease testing for C. difficile in young children and infants. DESIGN An interventional age-targeted before-after trial with comparison group SETTING Monroe Carell Jr. Children's Hospital at Vanderbilt University, Nashville, Tennessee. PATIENTS All children seen in the inpatient or emergency room settings from July 2012 through July 2013 (pre-CPOE alert) and September 2013 through September 2014 (post-CPOE alert) INTERVENTION In August of 2013, we implemented a CPOE alert advising against testing in infants and young children based on the American Academy of Pediatrics recommendations with an optional override. We further offered healthcare providers educational seminars regarding recommended C. difficile testing. RESULTS The average monthly testing rate significantly decreased after the CPOE alert for children 0-11 months old (11.5 pre-alert vs 0 post-alert per 10,000 patient days; P<.001) and 12-35 months old (61.6 pre-alert vs 30.1 post-alert per 10,000 patients days; P<.001), but not for those children ≥36 months old (50.9 pre-alert vs 46.4 post-alert per 10,000 patient days; P=.3) who were not targeted with a CPOE alert. There were no complications in those children who testing positive for C. difficile. CONCLUSIONS The average monthly testing rate for C. difficile for children <35 months old decreased without complication after the use of a CPOE alert in those who tested positive for C. difficile. Infect Control Hosp Epidemiol 2017;38:542-546.

The Empowering Schools Project: Identifying the Classroom and School Characteristics That Lead to Student Empowerment

Abstract: In an education system marred by inequity, urban schools in the United States are faced with the challenge of helping students from marginalized groups succeed. While many strategies have been tried, most are built on deficit-based models that blame students and teachers for a lack of achievement and ignore the role of power within the school setting. Building on the body of research on school climate, critical pedagogy, and empowering settings, the present study developed a model of student empowerment using a case study of an ethnically diverse urban high school in the midwestern United States. Participant observation, focus groups, and interviews were utilized to identify classroom and school characteristics related to student empowerment. Students reported equitable teacher–student relationships, integrated student leadership, and shared decision making. Similarly, school staff reported high staff empowerment and sense of community. The Student Empowerment Model is a useful framework for school improv...

Markers of Cardiovascular Dysfunction in Adolescents With Anorexia Nervosa.

Abstract: Background. Cardiovascular complications contribute to the high morbidity and mortality rate among children with anorexia nervosa (AN). Advances in cardiac imaging permit a more comprehensive assessment of myocardial performance in children that could not be previously obtained with conventional imaging. Myocardial strain analysis is an emerging quantitative echocardiographic technique to characterize global and regional ventricular function in children. Objective. To assess global and regional left ventricular (LV0 function in children newly diagnosed with AN with conventional and quantitative 2-dimensional speckle tracking echocardiographic (2DSTE)-derived strain imaging. Materials. In a cross-sectional study of 30 patients with AN (DSM-5) and 14 age-, sex-, and race-matched healthy children, markers of cardiovascular risk, conventional and 2DSTE measures of LV function, and structure were evaluated and compared. The AN cohort was further stratified by behavioral patterns (restrict, exercise, or purge). Results. Conventional measures and LV global strain were similar between controls and children with AN. A subgroup of AN children with purging behavior had LV remodeling characterized by significantly decreased LV mass index. Regional ventricular function at the apex, as measured by strain, was also decreased in all AN patients. Percent change from ideal body weight, body mass index Z-score, electrolyte profiles, heart rate, and blood pressure were similar. Conclusions. Subclinical regional ventricular dysfunction is present in children with AN. Ventricular remodeling exists in a subgroup of children with AN in association with purging behavior. Future studies may utilize strain imaging to identify those AN patients who are at an increased risk for developing significant cardiac dysfunction.

Diffuse midline gliomas with subclonal H3F3A K27M mutation and mosaic H3.3 K27M mutant protein expression

Abstract: mutant protein, and discuss the implications with regard to classification and grading. The first patient is a 30-year-old woman who presented with headaches and symptoms of increased intracranial pressure. Imaging demonstrated a heterogeneously enhancing mass centered in the right thalamus (Fig. 1a and Supplemental Fig. 1), and subtotal resection was performed. Sections demonstrated a highly cellular infiltrative astrocytic neoplasm with WHO grade IV histologic features including frequent mitoses, marked nuclear pleomorphism, palisading necrosis, and microvascular proliferation (Fig. 1c and Supplemental Fig. 2a, b). The tumor was negative for IDH1 R132H mutant protein immunostaining and showed somatic loss of ATRX expression diffusely in all tumor nuclei (Supplemental Fig. 2c). Immunohistochemistry for histone H3 K27M mutant protein revealed a mosaic staining pattern with expression seen in some but not all tumor cells (Fig. 1e and Supplemental Fig. 2d). While the majority of tumor cells lacked H3 K27M mutant protein expression, there were scattered large groups, small clusters, and admixed single cells that were positive. Immunohistochemistry for trimethylation of lysine-27 of histone H3 (H3K27me3) revealed an Diffuse midline gliomas are aggressive tumors centered in midline structures of the brain that most commonly occur in children and young adults [6]. They are genetically defined by the presence of K27M mutation in either the H3F3A or HIST1H3B genes, which encode the histone H3 variants H3.3 and H3.1, respectively [1]. Given their poor prognosis, the 2016 WHO Classification includes “Diffuse midline glioma, H3 K27M-mutant” as a WHO grade IV entity, even in cases where only lower-grade histologic features are present [4]. In all cases reported to date, H3 K27M mutation has been a clonal alteration in all regions of tumors assessed by sequencing, and immunostaining with antibodies against H3 K27M mutant protein has revealed uniform expression in all tumor cells [2, 5, 6]. Thus, it has been hypothesized that H3 K27M mutation is the earliest or initiating genetic alteration during gliomagenesis in these tumors. Here we describe two cases of diffuse midline glioma with subclonal H3F3A K27M mutation and mosaic expression of H3.3 K27M

Visceral Hyperalgesia: When to Consider Gabapentin Use in Neonates-Case Study and Review.

Abstract: Visceral hyperalgesia refers to increased pain sensation in response to gastrointestinal sensory stimulus. In neonates with neurological impairments, gabapentin has been successfully used as a treatment for visceral hyperalgesia in neonates. The authors describe a preterm infant with myelomeningocele and persistent neuropathic pain that manifested as irritability, hypertonicity, poor weight gain, and feeding intolerance. After exclusion of other etiologies, the diagnosis of visceral hyperalgesia was suspected and the infant was treated with gabapentin. Following appropriate titration to effect and close monitoring of side effects of gabapentin, he subsequently demonstrated improved tone, decreased irritability with feedings, and appropriate weight gain. In addition, the authors provide a review of the available literature of gabapentin use in neonates and offer suggestions on when to consider starting gabapentin in a neonate with neurological impairment and chronic unexplained gastrointestinal manifestations.

Payment Reform to Enhance Collaboration of Primary Care and Cardiology: A Review.

Abstract: Importance The US health care system faces an unsustainable trajectory of high costs and inconsistent outcomes. The fee-for-service payment model has contributed to inefficiency, and new payment methods are a promising approach to improving value. Health reforms are needed to increase patient access, reduce costs, and improve health care quality, and the landmark Medicare Access and CHIP Reauthorization Act presents a roadmap for reform. The product of a collaboration between primary care and cardiology clinicians, this review describes a conceptual approach to delivery and payment reforms that aim to better support primary care-cardiology comanagement of chronic cardiovascular disease (CVD). Observations Few existing alternative payment models specifically address long-term management of CVD. Primary care medical homes and accountable care organizations come closest, but both emphasize primary care, and cardiologists have often not been well engaged. A collaborative care framework should articulate distinct roles and responsibilities for primary care and cardiology in CVD comanagement. Finally, a series of payment models aim to better support clinicians in providing accountable, seamless, and patient-centered cardiac care. Conclusions & relevance Clinical leadership is essential during this time of change in the health care system. Patients often struggle to navigate a fragmented and expensive system, whereas clinicians often practice with incomplete information about tests, treatments, and recommendations by their colleagues. The payment models described in this review offer an opportunity to create more satisfying approaches to patient care while improving value. These models have potential to support more effective coordination and to facilitate broader health care system transformation.

Lower Urinary Tract Anomalies

Abstract: Urethral and bladder anomalies are commonly found during routine evaluation for hematuria, urinary tract infections, and other urological conditions. Many of these conditions present with voiding dysfunctions which may not only confound the diagnosis but also affect therapeutic options. Urodynamics are used in order to better understand baseline voiding function in urethral and bladder anomalies, as well as to better counsel patients and plan surgical repair. Herein we discuss both urethral and bladder anomalies, with case reports and urodynamic evaluations for each of these conditions.

Neuromuscular Complications in the Critically Ill Child

Abstract: Neurophysiologists may be asked to evaluate a child in the pediatric intensive care unit (PICU) with muscle weakness, hypotonia, or inability to recover from an underlying disease at the expected rate. Some children may be difficult to wean from mechanical ventilation or fail multiple attempts at extubation.