Related Developmental and Epileptic Encephalopathy: Phenotypic and Genotypic Spectrum.

Background And Objectives: Purine-rich element-binding protein A () gene encodes Pur-α, a conserved protein essential for normal postnatal brain development. Recently, a syndrome characterized by intellectual disability, hypotonia, epilepsy, and dysmorphic features was suggested. The aim of this study was to define and expand the phenotypic spectrum of syndrome by collecting data, including EEG, from a large cohort of affected patients.

Passive perinatal immunotherapy via transamniotic antibody delivery.

Purpose: We sought to determine whether the amniotic cavity/fluid could be an attainable route of administration of therapeutic antibodies to the fetus/neonate.

Methods: Time-dated pregnant dams (n = 9) received volume-matched intra-amniotic injections of either saline (n = 29), or different concentrations of a human IgG that lacked homology with rodents: 5 mg/mL (n = 28); 10 mg/mL (n = 28); or 15 mg/mL (n = 24). At term, the presence of the IgG was quantified by ELISA in the serum, bone marrow, spleen, thymus, and brain of all neonates, and in the maternal serum.

The brain and behavioral correlates of motor-related analgesia (MRA).

The human motor system has the capacity to act as an internal form of analgesia. Since the discovery of the potential influence of motor systems on analgesia in rodent models, clinical applications of targeting the motor system for analgesia have been implemented. However, a neurobiological basis for motor activation's effects on analgesia is not well defined.

Investigating the maturation of microstructure and radial orientation in the preterm human cortex with diffusion MRI.

Preterm birth disrupts and alters the complex developmental processes in the cerebral cortex. This disruption may be a contributing factor to widespread delay and cognitive difficulties in the preterm population. Diffusion-weighted magnetic resonance imaging (DW MRI) is a noninvasive imaging technique that makes inferences about cellular structures, at scales smaller than the imaging resolution.

Genome editing using FACS enrichment of nuclease-expressing cells and indel detection by amplicon analysis.

This protocol describes methods for increasing and evaluating the efficiency of genome editing based on the CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR-associated 9) system, transcription activator-like effector nucleases (TALENs) or zinc-finger nucleases (ZFNs). First, Indel Detection by Amplicon Analysis (IDAA) determines the size and frequency of insertions and deletions elicited by nucleases in cells, tissues or embryos through analysis of fluorophore-labeled PCR amplicons covering the nuclease target site by capillary electrophoresis in a sequenator. Second, FACS enrichment of cells expressing nucleases linked to fluorescent proteins can be used to maximize knockout or knock-in editing efficiencies or to balance editing efficiency and toxic/off-target effects.

A pediatric animal model to evaluate the effects of disuse on musculoskeletal growth and development.

Prolonged immobilization in hospitalized children can lead to fragility fractures and muscle contractures and atrophy. The purpose of this study was to develop a lower-extremity disuse rabbit model with musculoskeletal changes similar to those observed in children subjected to prolonged immobilization. Six-week-old rabbits were randomly assigned to control (CTRL, n=4) or bilateral sciatic and femoral neurectomy (bSFN, n=4) groups.

Large strain stimulation promotes extracellular matrix production and stiffness in an elastomeric scaffold model.

Mechanical conditioning of engineered tissue constructs is widely recognized as one of the most relevant methods to enhance tissue accretion and microstructure, leading to improved mechanical behaviors. The understanding of the underlying mechanisms remains rather limited, restricting the development of in silico models of these phenomena, and the translation of engineered tissues into clinical application. In the present study, we examined the role of large strip-biaxial strains (up to 50%) on ECM synthesis by vascular smooth muscle cells (VSMCs) micro-integrated into electrospun polyester urethane urea (PEUU) constructs over the course of 3 weeks.

Gastrointestinal Tract Perforation in the Newborn and Child: Imaging Assessment.

Gastrointestinal tract perforation can arise from various underlying etiologies ranging from congenital causes to ingested foreign bodies in the pediatric patient population. Imaging assessment in patients with suspected gastrointestinal tract perforation plays a central role in making the diagnosis and follow-up evaluation. This article reviews the more common etiologies of gastrointestinal tract perforation in pediatric patients, their imaging manifestations, and strategies for imaging assessment to assist the radiologist in arriving at a timely and accurate diagnosis.

Combined and complex vascular malformations.

The correct diagnosis of vascular malformations is obtainable by clinical assessment and patient history in the majority of cases. Nonetheless, confusion in nomenclature, existence of multiple classifications and rarity of these lesions leads to misdiagnosis and related wrong treatment. This is especially the case in combined or complex vascular malformations or vascular malformations that are part of syndromes as these have overlapping clinical and imaging features.

Tracheobronchial foreign bodies in children: imaging assessment.

Tracheobronchial foreign-body aspiration is a relatively frequent pediatric emergency and a cause of substantial morbidity and mortality especially in preschool children. Although foreign-body aspiration may cause sudden airway obstruction and subsequent death, quite often symptoms are mild and nonspecific; therefore, the correct diagnosis may be delayed particularly in the pediatric population. A delay in diagnosis increases the rate of complications and can cause substantial morbidity.

Vascular malformations revisited.

Vascular malformations are congenital anomalies that can affect each part of the vasculature. Combined forms are common and they are often part of complex syndromes. Most malformations are diagnosed during infancy, but some get obvious only later in life.

Overgrowth syndromes with complex vascular anomalies.

Management of overgrowth syndromes with complex vascular anomalies is challenging. Careful analysis of the various clinical features by an interdisciplinary team of physicians experienced in this field is paramount to proper diagnostic and therapeutic approaches. In this article, we focus on the spectrum of the clinical presentation and the management strategies of the most common overgrowth syndromes with complex vascular anomalies.

Arteriovenous malformations.

Arteriovenous malformations (AVMs) are fast-flow vascular malformations composed of a complex vessel network directly connecting feeding arteries to draining veins. The intervening normal capillary network is absent. Proper diagnosis and treatment of AVMs is challenging and in need of an interdisciplinary team of experienced physicians.

Angiogenesis: an organizing principle for drug discovery?

Angiogenesis--the process of new blood-vessel growth--has an essential role in development, reproduction and repair. However, pathological angiogenesis occurs not only in tumour formation, but also in a range of non-neoplastic diseases that could be classed together as 'angiogenesis-dependent diseases'. By viewing the process of angiogenesis as an 'organizing principle' in biology, intriguing insights into the molecular mechanisms of seemingly unrelated phenomena might be gained.

Oxygen and glucose deprivation-induced neuronal apoptosis is attenuated by halothane and isoflurane.

Unlabelled: Both in vitro and in vivo evidence supports the reduction of early ischemic, both global and focal, brain injury by volatile anesthetics. However, the protection afforded by volatile anesthetics in later neuronal death, i.e.

Congenital diaphragmatic hernia: where are we and where do we go from here?

The infant born with congenital diphragmatic hernia (CDH) remains one of the most complex patients to manage. Pulmonary hypoplasia and immaturity of the CDH lung are well recognized as the definitive limitation leading to the high mortality rates. Based on the knowledge that CDH is more a physiological disease than a surgical disease, we have shifted our management strategy from immediate repair to delayed repair and stabilization.

The relationship between membrane fluidity and permeabilities to water, solutes, ammonia, and protons.

Several barrier epithelia such as renal collecting duct, urinary bladder, and gastric mucosa maintain high osmotic pH and solute gradients between body compartments and the blood by means of apical membranes of exceptionally low permeabilities. Although the mechanisms underlying these low permeabilities have been only poorly defined, low fluidity of the apical membrane has been postulated. The solubility diffusion model predicts that lower membrane fluidity will reduce permeability by reducing the ability of permeant molecules to diffuse through the lipid bilayer.