Intracerebroventricular administration of a modified hexosaminidase ameliorates late-stage neurodegeneration in a GM2 mouse model.

The GM2 gangliosidoses, Tay-Sachs disease and Sandhoff disease, are devastating neurodegenerative disorders caused by β-hexosaminidase A (HexA) deficiency. In the Sandhoff disease mouse model, rescue potential was severely reduced when HexA was introduced after disease onset. Here, we assess the effect of recombinant HexA and HexD3, a newly engineered mimetic of HexA optimized for the treatment of Tay-Sachs disease and Sandhoff disease.

Galactokinase 1 is the source of elevated galactose-1-phosphate and cerebrosides are modestly reduced in a mouse model of classic galactosemia.

Classic galactosemia (CG) arises from loss-of-function mutations in the gene, which codes for the enzyme galactose-1-phosphate uridylyltransferase (GALT), a central component in galactose metabolism. The neonatal fatality associated with CG can be prevented by galactose dietary restriction, but for decades it has been known that limiting galactose intake is not a cure and patients often have lasting complications. Even on a low-galactose diet, GALT's substrate galactose-1-phosphate (Gal1P) is elevated and one hypothesis is that elevated Gal1P is a driver of pathology.

Case report: Is bilateral renal dioctophymosis and severe uremia in a dog synonymous of euthanasia? Not today.

A dog with bilateral renal dioctophymosis presented with stage 5 acute kidney injury, weight loss, vomiting, apathy, and hematuria. Laboratory tests showed creatinine of 17.2 mg/dL and eggs in the urine.

Sedative and cardiorespiratory effects of dexmedetomidine alone or combined with acepromazine in healthy cats.

The purpose of this study was to assess sedation, emesis and cardiovascular effects of dexmedetomidine alone or combined with acepromazine in healthy cats. Fourteen male cats aged 0.9 ± 0.

Prophylactic Prednisolone Promotes AAV5 Hepatocyte Transduction Through the Novel Mechanism of AAV5 Coreceptor Platelet-Derived Growth Factor Receptor Alpha Upregulation and Innate Immune Suppression.

Adeno-associated virus (AAV) vectors are used to deliver therapeutic transgenes, but host immune responses may interfere with transduction and transgene expression. We evaluated prophylactic corticosteroid treatment on AAV5-mediated expression in liver tissue. Wild-type C57BL/6 mice received 6 × 10 vg/kg AAV5-HLP-hA1AT, an AAV5 vector carrying a human α1-antitrypsin (hA1AT) gene with a hepatocyte-specific promoter.

Intracerebroventricular dosing of N-sulfoglucosamine sulfohydrolase in mucopolysaccharidosis IIIA mice reduces markers of brain lysosomal dysfunction.

Mucopolysaccharidosis type IIIA (MPS IIIA) is a lysosomal storage disorder caused by N-sulfoglucosamine sulfohydrolase (SGSH) deficiency. SGSH removes the sulfate from N-sulfoglucosamine residues on the nonreducing end of heparan sulfate (HS-NRE) within lysosomes. Enzyme deficiency results in accumulation of partially degraded HS within lysosomes throughout the body, leading to a progressive severe neurological disease.

Biochemical evaluation of intracerebroventricular rhNAGLU-IGF2 enzyme replacement therapy in neonatal mice with Sanfilippo B syndrome.

Mucopolysaccharidosis IIIB (MPS IIIB, Sanfilippo syndrome type B) is caused by a deficiency in α-N-acetylglucosaminidase (NAGLU) activity, which leads to the accumulation of heparan sulfate (HS). MPS IIIB causes progressive neurological decline, with affected patients having an expected lifespan of approximately 20 years. No effective treatment is available.

Food insecurity and the extremes of childhood weight: defining windows of vulnerability.

Background: Weight extremes and food insecurity (FIS) represent public-health challenges, yet their associations in childhood remain unclear. We aimed to investigate the longitudinal time-specific relationship between FIS and risk of overweight/obesity and underweight in kindergarten through 8th grade.

Methods: In the prospective Early Childhood Longitudinal Study-Kindergarten Cohort (1998-2007) of 6368 children, household FIS was assessed by the validated US Household Food Security Survey Module in kindergarten, 3rd, 5th and 8th grades.

Characterization of glycan substrates accumulating in GM1 Gangliosidosis.

Introduction: GM1 gangliosidosis is a rare autosomal recessive genetic disorder caused by the disruption of the gene that encodes β-galactosidase, a lysosomal hydrolase that removes β-linked galactose from the non-reducing end of glycans. Deficiency of this catabolic enzyme leads to the lysosomal accumulation of GM1 and its asialo derivative GA1 in β-galactosidase deficient patients and animal models. In addition to GM1 and GA1, there are other glycoconjugates that contain β-linked galactose whose metabolites are substrates for β-galactosidase.

Gallic acid prevents ketamine-induced oxidative damages in brain regions and liver of rats.

Introduction: Ketamine (KET) is an anesthetic agent widely used in human and veterinary medicine. According to studies, KET is associated to direct neutorotoxic damages due to its capacity to induce oxidative stress. Because of the free radical generation in the organism and its relation with diseases' development, there is a growing interest to study antioxidant molecules, such as gallic acid (GA), a natural phenolic compound.

Intracerebroventricular enzyme replacement therapy with β-galactosidase reverses brain pathologies due to GM1 gangliosidosis in mice.

Autosomal recessive mutations in the galactosidase β1 () gene cause lysosomal β-gal deficiency, resulting in accumulation of galactose-containing substrates and onset of the progressive and fatal neurodegenerative lysosomal storage disease, GM1 gangliosidosis. Here, an enzyme replacement therapy (ERT) approach in fibroblasts from GM1 gangliosidosis patients with recombinant human β-gal (rhβ-gal) produced in Chinese hamster ovary cells enabled direct and precise rhβ-gal delivery to acidified lysosomes. A single, low dose (3 nm) of rhβ-gal was sufficient for normalizing β-gal activity and mediating substrate clearance for several weeks.

Timing of household food insecurity exposures and asthma in a cohort of US school-aged children.

Objective: Food insecurity is positively associated with asthma, the most common chronic childhood disease, yet directionality is unclear. The objective was to determine the association between exposure to food insecurity in early childhood and the odds of asthma later in childhood.

Design: Data from four waves of the Early Childhood Longitudinal Study-Kindergarten (ECLS-K) cohort, a prospective, dual-frame, multistage probability cluster sampling study of school-aged US children were entered in multivariate logistic regression models, adjusted for covariates.

Peripheral perfusion index does not accurately reflect hypoperfusion in healthy dogs undergoing elective ovariohysterectomy.

This study evaluated the variability of the peripheral perfusion index (PI) in 22 anaesthetised female dogs undergoing elective ovariohysterectomy and examined the relationship between peripheral PI and heart rate, blood pressure, blood pH, end tidal CO (EtCO), O saturation (SpO), core-peripheral temperature gradient (ΔTc-p), partial pressure of CO (PCO), and concentrations of glucose, cortisol, lactate and bicarbonate (HCO). Blood pH, lactate and glucose concentrations were determined 15, 30, 45min into the ovariohysterectomy procedure and after extubation. Cortisol concentrations were assessed before anaesthesia and after extubation.

Food Insecurity and Hunger: Quiet Public Health Problems on Campus.

Food insecurity and hunger are gaining traction as recognized public health problems on college campuses in the United States. Data from recent publications and reports suggest the prevalence of food insecurity among U.S.

Wandering: Unearthing New Tracking Devices.

Wandering away from home or facilities is dangerous for patients with dementia and stressful for families and caregivers when those who go missing cannot be located. Up to 60% of Alzheimer's disease patients wander, and up to 50% of those who are not found within 24 hours face serious injury or death. Currently, no effective drug therapies exist to abate wandering, which has multiple causes, but emerging technologies offer a promise of comfort in being able to easily locate a missing loved one.

From the Cover: BDE-47 and BDE-49 Inhibit Axonal Growth in Primary Rat Hippocampal Neuron-Glia Co-Cultures via Ryanodine Receptor-Dependent Mechanisms.

Polybrominated diphenyl ethers (PBDEs) are widespread environmental contaminants associated with adverse neurodevelopmental outcomes in children and preclinical models; however, the mechanisms by which PBDEs cause developmental neurotoxicity remain speculative. The structural similarity between PBDEs and nondioxin-like (NDL) polychlorinated biphenyls (PCBs) suggests shared toxicological properties. Consistent with this, both NDL PCBs and PBDEs have been shown to stabilize ryanodine receptors (RyRs) in the open configuration.

Household Food Insecurity is Associated with Childhood Asthma.

Background: In 2013, 20% of U.S. households with children experienced food insecurity.

CARES: improving the care and disposition of psychiatric patients in the pediatric emergency department.

Objectives: Pediatric psychiatric emergencies are a nationwide crisis and have contributed to an increase in behavioral health emergency department (ED) visits. A collaborative response to this crisis was the creation of the Child & Adolescent Rapid Emergency Stabilization (CARES) program. The objective of this study is to determine how the CARES unit influenced length of stay (LOS) and costs for psychiatric patients in the pediatric ED.

Life-course origins of the ages at menarche and menopause.

A woman's age at menarche (first menstrual period) and her age at menopause are the alpha and omega of her reproductive years. The timing of these milestones is critical for a woman's health trajectory over her lifespan, as they are indicators of ovarian function and aging. Both early and late timing of either event are associated with risk for adverse health and psychosocial outcomes.

IFNγ Increases M2 Muscarinic Receptor Expression in Cultured Sympathetic Neurons.

M2 muscarinic receptors are expressed on both parasympathetic and sympathetic nerve endings where they function as autoinhibitory receptors to limit release of acetylcholine and norepinephrine, respectively. M2 muscarinic receptor expression on parasympathetic nerves is decreased by viral infection and by gamma-interferon (IFNγ) and increased by dexamethasone; and these effects are of clinical relevance in the etiology and treatment of asthma. Whether IFNγ and dexamethasone similarly modulate M2 receptor expression on sympathetic nerves is not known.

The Symptom Experience of HIV/HCV-Coinfected Adults.

Hepatitis C virus (HCV) infection has emerged as a major problem for adults with HIV infection. This report describes the symptom experience of HIV/HCV-coinfected adults at entry into a longitudinal mixed-method study. In-depth qualitative interviews and a standardized quantitative symptom measure were used to capture the symptom experiences of 39 (46% women) HIV/HCV-coinfected patients.

MBR pilot plant for textile wastewater treatment and reuse.

An experimental study was carried out in order to evaluate the possibility of upgrading the conventional activated sludge WWTP of Seano (Prato, Italy) which treats municipal and textile wastewaters, by using membrane bioreactor (MBR) technology. The MBR pilot plant, set up within Seano WWTP, was fed with mixed municipal-industrial wastewaters during the first experimental period and with pure industrial wastewaters during the second. Performances and operation of the MBR were evaluated in terms of permeate characteristics and variability (COD, colour, surfactants, total N and P) and other operational parameters (sludge growth and observed yield).

Targeting symptom domains: a strategy for pharmacotherapy in childhood pervasive developmental disorders.

This article summarizes clinical guidelines and reviews psychopharmacologic studies involving children and adolescents with Pervasive Developmental Disorders (PDDs). Strategies are drawn from basic principles of pediatric psychopharmacology, nonpharmacological approaches to the treatment of PDDs, and practical clinical experience in an attempt to provide the practitioner with an evidence-based approach to utilizing pharmacotherapy in children and adolescents with PDDs. Although early identification followed by intensive educational and behavioral interventions remains the essential treatment of PDDs, there is evidence to support the identification of target behaviors or symptom domains, for medication.

Neonatal isolation stress potentiates cocaine seeking behavior in adult male and female rats.

Little is known with regard to how sex and stress might interact as vulnerability factors in cocaine abuse. In this study, we compared the effects of neonatal isolation stress on cocaine self-administration under extended access conditions and on subsequent responding in a cue-induced reinstatement paradigm in adult male and female rats. Pups from each litter were subjected to either neonatal isolation (1 h/day) or brief daily handling from postnatal day 2 through 12.