Plasmoid Formation and Strong Radiative Cooling in a Driven Magnetic Reconnection Experiment.

We present the first experimental study of plasmoid formation in a magnetic reconnection layer undergoing rapid radiative cooling, a regime relevant to extreme astrophysical plasmas. Two exploding aluminum wire arrays, driven by the Z machine, generate a reconnection layer (S_{L}≈120) in which the cooling rate far exceeds the hydrodynamic transit rate (τ_{hydro}/τ_{cool}>100). The reconnection layer generates a transient burst of >1 keV x-ray emission, consistent with the formation and subsequent rapid cooling of the layer. Time-gated x-ray images show fast-moving (up to 50 km s^{-1}) hotspots in the layer, consistent with the presence of plasmoids in 3D resistive magnetohydrodynamic simulations. X-ray spectroscopy shows that these hotspots generate the majority of Al K-shell emission (around 1.6 keV) prior to the onset of cooling, and exhibit temperatures (170 eV) much greater than that of the plasma inflows and the rest of the reconnection layer, thus providing insight into the generation of high-energy radiation in radiatively cooled reconnection events.

Examining the immunoepigenetic-gut microbiome axis in the context of self-esteem among Native Hawaiians and other Pacific Islanders.

Introduction: Native Hawaiian and other Pacific Islander (NHPI) populations experience higher rates of immunometabolic diseases compared to other racial-ethnic groups in Hawaii. As annual NHPI mortality rates for suicide and type 2 diabetes mellitus (T2DM) exceed those of the state as a whole, understanding the social and biological mechanisms underlying these disparities are urgently needed to enable preventive strategies. Methods: A community-based approach was used to investigate the immunoepigenetic-gut microbiome axis in an NHPI-enriched cohort of Oahu residents (N = 68). Self-esteem (SE) data was collected using a modified Rosenberg self-esteem (SE) assessment as a proxy measure for mental wellbeing in consideration for cultural competency. T2DM status was evaluated using point-of-care A1c (%) tests. Stool samples were collected for 16s-based metagenomic sequencing analyses. Plasma from blood samples were isolated by density-gradient centrifugation. Peripheral blood mononuclear cells (PBMCs) were collected from the same samples and enriched for monocytes using negative selection techniques. Flow-cytometry was used for immunoprofiling assays. Monocyte DNA was extracted for Illumina EPIC array-based methylation analysis. Results: Compared to individuals with normal SE (NSE), those with low SE (LSE) exhibited significantly higher plasma concentrations (pg/ml) of proinflammatory cytokines IL-8 (p = 0.051) and TNF-α (p = 0.011). Metagenomic analysis revealed that the relative abundance (%) of specific gut bacteria significantly differed between SE groups - some of which directly correlated with SE scores. Gene ontology analysis revealed that 104 significantly differentially methylated loci (DML) between SE groups were preferentially located at genes involved in immunometabolic processes. Horvath clock analyses indicated epigenetic age (Epi-Age) deceleration in individuals with LSE and acceleration in individuals with NSE (p = 0.042), yet was not reproduced by other clocks. Discussion: These data reveal novel differences in the immunoepigenetic-gut microbiome axis with respect to SE, warranting further investigation into its relationship to brain activity and mental health in NHPI. Unexpected results from Epi-Age analyses warrant further investigation into the relationship between biological age and disparate health outcomes among the NHPI population. The modifiable component of epigenetic processes and the gut microbiome makes this axis an attractive target for potential therapeutics, biomarker discovery, and novel prevention strategies.

High-resolution fiber imaging for pulsed power experiments.

This work presents a novel approach for imaging the visible emissions from plasmas in pulsed power experiments using high-resolution plastic optical fibers. The diagnostic consists of a 2 mm diameter core commercial cable constructed of 13 000 individual acrylic fibers. The fibers are fused together to create a single high-resolution bundle. Different designs were investigated to cover a wide range of resolutions and fields of view (3-700 µm and 0.05-45 mm, respectively). The system was tested on the 1-MA Mykonos accelerator at Sandia National Laboratories and successfully imaged visible emission from a hybrid x-pinch target. Diagnostic development and preliminary results are presented.

GABAA Alpha 2,3 Modulation Improves Select Phenotypes in a Mouse Model of Fragile X Syndrome.

Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability. FXS is caused by functional loss of the Fragile X Protein (FXP), also known as Fragile X Mental Retardation Protein (FMRP). In humans and animal models, loss of FXP leads to sensory hypersensitivity, increased susceptibility to seizures and cortical hyperactivity. Several components of the GABAergic system, the major inhibitory system in the brain, are dysregulated in FXS, and thus modulation of GABAergic transmission was suggested and tested as a treatment strategy. However, so far, clinical trials using broad spectrum GABAA or GABAB receptor-specific agonists have not yielded broad improvement of FXS phenotypes in humans. Here, we tested a more selective strategy in Fmr1 knockout (KO) mice using the experimental drug BAER-101, which is a selective GABAA α2/α3 agonist. Our results suggest that BAER-101 reduces hyperexcitability of cortical circuits, partially corrects increased frequency-specific baseline cortical EEG power, reduces susceptibility to audiogenic seizures and improves novel object memory. Other Fmr1 KO-specific phenotypes were not improved by the drug, such as increased hippocampal dendritic spine density, open field activity and marble burying. Overall, this work shows that BAER-101 improves select phenotypes in Fmr1 KO mice and encourages further studies into the efficacy of GABAA-receptor subunit-selective agonists for the treatment of FXS.

De novo variants in MED12 cause X-linked syndromic neurodevelopmental disorders in 18 females.

PURPOSE: MED12 is a subunit of the Mediator multiprotein complex with a central role in RNA polymerase II transcription and regulation of cell growth, development, and differentiation. This might underlie the variable phenotypes in males carrying missense variants in MED12, including X-linked recessive Ohdo, Lujan, and FG syndromes. METHODS: By international matchmaking we assembled variant and clinical data on 18 females presenting with variable neurodevelopmental disorders (NDDs) and harboring de novo variants in MED12. RESULTS: Five nonsense variants clustered in the C-terminal region, two splice variants were found in the same exon 8 splice acceptor site, and 11 missense variants were distributed over the gene/protein. Protein truncating variants were associated with a severe, syndromic phenotype consisting of intellectual disability (ID), facial dysmorphism, short stature, skeletal abnormalities, feeding difficulties, and variable other abnormalities. De novo missense variants were associated with a less specific, but homogeneous phenotype including severe ID, autistic features, limited speech and variable other anomalies, overlapping both with females with truncating variants as well as males with missense variants. CONCLUSION: We establish de novo truncating variants in MED12 as causative for a distinct NDD and de novo missense variants as causative for a severe, less specific NDD in females.

Multilayer and Surface Immobilization of EDOT-Decorated Nanocapsules.

To assess the feasibility of utilizing reagent-loaded, porous polymeric nanocapsules (NCs) for chemical and biochemical sensor design, the surfaces of the NCs were decorated with 3,4-ethylenedioxythiophene (EDOT) moieties. The pores in the capsule wall allow unhindered bidirectional diffusion of molecules smaller than the programmed pore sizes, while larger molecules are either entrapped inside or blocked from entering the interior of the nanocapsules. Here, we investigate two electrochemical deposition methods to covalently attach acrylate-based porous nanocapsules with 3,4-ethylenedioxythiophene moieties on the nanocapsule surface, i.e., EDOT-decorated NCs to the surface of an existing PEDOT film: (1) galvanostatic or bilayer deposition with supporting EDOT in the deposition solution and (2) potentiostatic deposition without supporting EDOT in the deposition solution. The distribution of the covalently attached NCs in the PEDOT films was studied by variable angle FTIR-ATR and XPS depth profiling. The galvanostatic deposition of EDOT-decorated NCs over an existing PEDOT (tetrakis(pentafluorophenyl)borate) [PEDOT(TPFPhB)] film resulted in a bilayer structure, with an interface between the NC-free and NC-loaded layers, that could be traced with variable angle FTIR-ATR measurements. In contrast, the FTIR-ATR and XPS analyses of the films deposited potentiostatically from a solution without EDOT and containing only the EDOT-decorated NCs showed small amounts of NCs in the entire cross section of the films.

Benchmarking GPCR homology model template selection in combination with de novo loop generation.

G protein-coupled receptors (GPCR) comprise the largest family of membrane proteins and are of considerable interest as targets for drug development. However, many GPCR structures remain unsolved. To address the structural ambiguity of these receptors, computational tools such as homology modeling and loop modeling are often employed to generate predictive receptor structures. Here we combined both methods to benchmark a protocol incorporating homology modeling based on a locally selected template and extracellular loop modeling that additionally evaluates the presence of template ligands during these modeling steps. Ligands were also docked using three docking methods and two pose selection methods to elucidate an optimal ligand pose selection method. Results suggest that local template-based homology models followed by loop modeling produce more accurate and predictive receptor models than models produced without loop modeling, with decreases in average receptor and ligand RMSD of 0.54 Å and 2.91 Å, respectively. Ligand docking results showcased the ability of MOE induced fit docking to produce ligand poses with atom root-mean-square deviation (RMSD) values at least 0.20 Å lower (on average) than the other two methods benchmarked in this study. In addition, pose selection methods (software-based scoring, ligand complementation) selected lower RMSD poses with MOE induced fit docking than either of the other methods (averaging at least 1.57 Å lower), indicating that MOE induced fit docking is most suited for docking into GPCR homology models in our hands. In addition, target receptor models produced with a template ligand present throughout the modeling process most often produced target ligand poses with RMSD values ≤ 4.5 Å and Tanimoto coefficients > 0.6 after selection based on ligand complementation than target receptor models produced in the absence of template ligands. Overall, the findings produced by this study support the use of local template homology modeling in combination with de novo ECL2 modeling in the presence of a ligand from the template crystal structure to generate GPCR models intended to study ligand binding interactions.

GPCR homology model template selection benchmarking: Global versus local similarity measures.

G protein-coupled receptors (GPCR) are integral membrane proteins of considerable interest as targets for drug development. GPCR ligand interaction studies often have a starting point with either crystal structures or comparative models. The majority of GPCR do not have experimentally-characterized 3-dimensional structures, so comparative modeling, also called homology modeling, is a good structure-based starting point. Comparative modeling is a widely used method for generating models of proteins with unknown structures by analogy to crystallized proteins that are expected to exhibit structural conservation. Traditionally, comparative modeling template selection is based on global sequence identity and shared function. However high sequence identity localized to the ligand binding pocket may produce better models to examine protein-ligand interactions. This in silico benchmark study examined the performance of a global versus local similarity measure applied to comparative modeling template selection for 6 previously crystallized, class A GCPR (CXCR4, FFAR1, NOP, P2Y12, OPRK, and M1) with the long-term goal of optimizing GPCR ligand identification efforts. Comparative models were generated from templates selected using both global and local similarity measures. Similarity to reference crystal structures was reflected in RMSD values between atom positions throughout the structure or localized to the ligand binding pocket. Overall, models deviated from the reference crystal structure to a similar degree regardless of whether the template was selected using a global or local similarity measure. Ligand docking simulations were performed to assess relative performance in predicting protein-ligand complex structures and interaction networks. Calculated RMSD values between ligand poses from docking simulations and crystal structures indicate that models based on locally selected templates give docked poses that better mimic crystallographic ligand positions than those based on globally-selected templates in five of the six benchmark cases. However, protein model refinement strategies in advance of ligand docking applications are clearly essential as the average RMSD between crystallographic poses and poses docked into local template models was 9.7 Šand typically less than half of the ligand interaction sites are shared between the docked and crystallographic poses. These data support the utilization of local similarity measures to guide template selection in protocols using comparative models to investigate ligand-receptor interactions.

The first 142 amino acids of glutamate decarboxylase do not contribute to epitopes recognized by autoantibodies associated with Type 1 diabetes.

AIMS: Glutamate decarboxylase (GAD) antibodies are the most widely used predictive marker for Type 1 diabetes, but many individuals currently found to be GAD antibody-positive are unlikely to develop diabetes. We have shown previously that radioimmunoassays using N-terminally truncated 35 S-GAD65 (96-585) offer better disease specificity with similar sensitivity to full-length 35 S-GAD65 (1-585). To determine whether assay performance could be improved further, we evaluated a more radically truncated 35 S-GAD65 (143-585) radiolabel. METHODS: Samples from people with recent-onset Type 1 diabetes (n = 157) and their first-degree relatives (n = 745) from the Bart's-Oxford family study of childhood diabetes were measured for GAD antibodies using 35 S-labelled GAD65 (143-585). These were screened previously using a local radioimmunoassay with 35 S-GAD65 (1-585). A subset was also tested by enzyme-linked immunosorbent assay (ELISA), which performs well in international workshops, but requires 10 times more serum. Results were compared with GAD antibody measurements using 35 S-GAD65 (1-585) and 35 S-GAD65 (96-585). RESULTS: Sensitivity of GAD antibody measurement was maintained using 35 S-GAD65 (143-585) compared with 35 S-GAD65 (1-585) and 35 S-GAD65 (96-585). Specificity for Type 1 diabetes was improved compared with 35 S-GAD65 (1-585), but was similar to 35 S-GAD65 (96-585). Relatives found to be GAD antibody-positive using these truncated labels were at increased risk of diabetes progression within 15 years, compared with those positive for GAD(1-585) antibody only, and at similar risk to those found GAD antibody-positive by ELISA. CONCLUSIONS: The first 142 amino acids of GAD65 do not contribute to epitopes recognized by Type 1 diabetes-associated GAD antibodies. Low-volume radioimmunoassays using N-terminally truncated 35 S-GAD65 are more specific than those using full-length GAD65 and offer practical alternatives to the GAD antibody ELISA for identifying children at increased risk of Type 1 diabetes.

A quarter of patients with type 1 diabetes have co-existing non-islet autoimmunity: the findings of a UK population-based family study.

Individuals with type 1 diabetes (T1D) are at increased risk of coeliac disease (CD), autoimmune thyroiditis and autoimmune gastritis, but the absolute risks are unclear. The aim of this study was to investigate the prevalence of autoantibodies to tissue transglutaminase (TGA), thyroid peroxidase (TPOA) and gastric H+ /K+ -ATPase (ATPA) and their genetic associations in a well-characterized population-based cohort of individuals with T1D from the Bart's-Oxford family study for whom islet autoantibody prevalence data were already available. Autoantibodies in sera from 1072 patients (males/females 604/468; median age 11·8 years, median T1D duration 2·7 months) were measured by radioimmunoassays; HLA class II risk genotype was analysed in 973 (91%) using polymerase chain reaction with sequence specific primers (PCR-SSP). The prevalence of TGA (and/or history of CD), TPOA and ATPA in patients was 9·0, 9·6 and 8·2%, respectively; 3·1% had two or more autoantibodies. Females were at higher risk of multiple autoimmunity; TGA/CD were associated with younger age and TPOA with older age. ATPA were uncommon in patients under 5 years, and more common in older patients. Anti-glutamate decarboxylase autoantibodies were predictive of co-existing TPOA/ATPA. TGA/CD were associated with human leucocyte antigen (HLA) DR3-DQ2, with the DR3-DQ2/DR3-DQ2 genotype conferring the highest risk, followed by DR4-DQ8/DR4-DQ8. ATPA were associated with DR3-DQ2, DRB1*0404 (in males) and the DR3-DQ2/DR4-DQ8 genotype. TPOA were associated with the DR3-DQ2/DR3-DQ2 genotype. Almost one-quarter of patients diagnosed with T1D aged under 21 years have at least one other organ-specific autoantibody. HLA class II genetic profiling may be useful in identifying those at risk of multiple autoimmunity.

Acamprosate in a mouse model of fragile X syndrome: modulation of spontaneous cortical activity, ERK1/2 activation, locomotor behavior, and anxiety.

BACKGROUND: Fragile X Syndrome (FXS) occurs as a result of a silenced fragile X mental retardation 1 gene (FMR1) and subsequent loss of fragile X mental retardation protein (FMRP) expression. Loss of FMRP alters excitatory/inhibitory signaling balance, leading to increased neuronal hyperexcitability and altered behavior. Acamprosate (the calcium salt of N-acetylhomotaurinate), a drug FDA-approved for relapse prevention in the treatment of alcohol dependence in adults, is a novel agent with multiple mechanisms that may be beneficial for people with FXS. There are questions regarding the neuroactive effects of acamprosate and the significance of the molecule's calcium moiety. Therefore, the electrophysiological, cellular, molecular, and behavioral effects of acamprosate were assessed in the Fmr1-/y (knock out; KO) mouse model of FXS controlling for the calcium salt in several experiments. METHODS: Fmr1 KO mice and their wild-type (WT) littermates were utilized to assess acamprosate treatment on cortical UP state parameters, dendritic spine density, and seizure susceptibility. Brain extracellular-signal regulated kinase 1/2 (ERK1/2) activation was used to investigate this signaling molecule as a potential biomarker for treatment response. Additional adult mice were used to assess chronic acamprosate treatment and any potential effects of the calcium moiety using CaCl2 treatment on behavior and nuclear ERK1/2 activation. RESULTS: Acamprosate attenuated prolonged cortical UP state duration, decreased elevated ERK1/2 activation in brain tissue, and reduced nuclear ERK1/2 activation in the dentate gyrus in KO mice. Acamprosate treatment modified behavior in anxiety and locomotor tests in Fmr1 KO mice in which control-treated KO mice were shown to deviate from control-treated WT mice. Mice treated with CaCl2 were not different from saline-treated mice in the adult behavior battery or nuclear ERK1/2 activation. CONCLUSIONS: These data indicate that acamprosate, and not calcium, improves function reminiscent of reduced anxiety-like behavior and hyperactivity in Fmr1 KO mice and that acamprosate attenuates select electrophysiological and molecular dysregulation that may play a role in the pathophysiology of FXS. Differences between control-treated KO and WT mice were not evident in a recognition memory test or in examination of acoustic startle response/prepulse inhibition which impeded conclusions from being made about the treatment effects of acamprosate in these instances.

Delineating the phenotypic spectrum of Bainbridge-Ropers syndrome: 12 new patients with de novo, heterozygous, loss-of-function mutations in ASXL3 and review of published literature.

BACKGROUND: Bainbridge-Ropers syndrome (BRPS) is a recently described developmental disorder caused by de novo truncating mutations in the additional sex combs like 3 (ASXL3) gene. To date, there have been fewer than 10 reported patients. OBJECTIVES: Here, we delineate the BRPS phenotype further by describing a series of 12 previously unreported patients identified by the Deciphering Developmental Disorders study. METHODS: Trio-based exome sequencing was performed on all 12 patients included in this study, which found a de novo truncating mutation in ASXL3. Detailed phenotypic information and patient images were collected and summarised as part of this study. RESULTS: By obtaining genotype:phenotype data, we have been able to demonstrate a second mutation cluster region within ASXL3. This report expands the phenotype of older patients with BRPS; common emerging features include severe intellectual disability (11/12), poor/ absent speech (12/12), autistic traits (9/12), distinct face (arched eyebrows, prominent forehead, high-arched palate, hypertelorism and downslanting palpebral fissures), (9/12), hypotonia (11/12) and significant feeding difficulties (9/12) when young. DISCUSSION: Similarities in the patients reported previously in comparison with this cohort included their distinctive craniofacial features, feeding problems, absent/limited speech and intellectual disability. Shared behavioural phenotypes include autistic traits, hand-flapping, rocking, aggressive behaviour and sleep disturbance. CONCLUSIONS: This series expands the phenotypic spectrum of this severe disorder and highlights its surprisingly high frequency. With the advent of advanced genomic screening, we are likely to identify more variants in this gene presenting with a variable phenotype, which this study will explore.

Two patients with chromosome 22q11.2 deletion presenting with childhood obesity and hyperphagia.

Chromosome 22q11.2 deletion syndrome is a clinically heterogeneous condition of intellectual disability, parathyroid and thyroid hypoplasia, palatal abnormalities, cardiac malformations and psychiatric symptoms. Hyperphagia and childhood obesity is widely reported in Prader-Willi Syndrome (PWS) but there is only one previous report of this presentation in chromosome 22q11.2 deletion syndrome. We describe two further cases of chromosome 22q11.2 deletion syndrome in which hyperphagia and childhood obesity were the presenting features. This may be a manifestation of obsessive behaviour secondary to some of the psychiatric features commonly seen in chromosome 22q11.2 deletion syndrome. Serious complications may result from hyperphagia and childhood obesity therefore early recognition and intervention is crucial. Due to the similar clinical presentation of these two patients to patients with PWS, it is suggested that the hyperphagia seen here should be managed in a similar way to how it is managed in PWS.

Fanconi anaemia: genetics, molecular biology, and cancer ­ implications for clinical management in children and adults.

Fanconi anaemia (FA) is an inherited disease with congenital and developmental abnormalities, cross-linker hypersensitivity and extreme cancer predisposition. With better understanding of the genetic and molecular basis of the disease, and improved clinical management, FA has been transformed from a life-limiting paediatric disease to an uncommon chronic condition that needs lifelong multidisciplinary management, and a paradigm condition for the understanding of the gene-environment interaction in the aetiology of congenital anomalies, haematopoiesis and cancer development. Here we review genetic, molecular and clinical aspects of FA, and discuss current controversies and future prospects.

Maternal hepatitis B and hepatitis C infection and neonatal neurological outcomes.

To examine the associations between maternal hepatitis B (HBV) and hepatitis C (HCV) infection status and selected infant neurological outcomes diagnosed at birth, we conducted a population-based, retrospective cohort study on singleton live births in Florida from 1998 to 2009. Primary exposures included maternal HBV and HCV monoinfection. The neurological outcomes included brachial plexus injury, cephalhematoma, foetal distress, feeding difficulties, intraventricular h aemorrhage and neonatal seizures. Multivariable logistic regression models were used to generate odds ratios (OR) and 95% confidence intervals (CI) that were adjusted for socio-demographic characteristics, risky behaviours, pregnancy complications and pre-existing medical conditions, and timing of delivery. The risk of an adverse neurological outcome was higher in infants born to mothers with hepatitis viral infection (7.2% for HCV, 5.0% for HBV), compared with infants of hepatitis virus-free mothers (4.2%). After adjusting for potential confounders, women with HBV were twice as likely to have infants who suffered from brachial plexus injury (OR = 2.04, 95% CI = 1.15-3.60), while those with HCV had an elevated odds of having an infant with feeding difficulties (OR: 1.32, 95% CI = 1.06-1.64) and a borderline increased likelihood for neonatal seizures (OR = 1.74, 95% CI = 0.98-3.10). Additionally, HCV+ mothers had a 22% increased odds of having an infant with some type of adverse neurological outcome (OR: 1.22, 95% CI = 1.03-1.44). Our findings add to current understanding of the association between maternal HBV/HCV infections and infant neurological outcomes. Further research evaluating the role of maternal HBV and HCV infections (including viraemia, treatment) on pregnancy outcomes is warranted.

MLL2 mosaic mutations and intragenic deletion-duplications in patients with Kabuki syndrome.

Kabuki syndrome (KS) is a rare multi-system disorder that can result in a variety of congenital malformations, typical dysmorphism and variable learning disability. It is caused by MLL2 point mutations in the majority of the cases and, rarely by deletions involving KDM6A. Nearly one third of cases remain unsolved. Here, we expand the known genetic basis of KS by presenting five typical patients with the condition, all of whom have novel MLL2 mutation types- two patients with mosaic small deletions, one with a mosaic whole-gene deletion, one with a multi-exon deletion and one with an intragenic multi-exon duplication. We recommend MLL2 dosage studies for all patients with typical KS, where traditional Sanger sequencing fails to identify mutations. The prevalence of such MLL2 mutations in KS may be comparable with deletions involving KDM6A. These findings may be helpful in understanding the mutational mechanism of MLL2 and the disease mechanism of KS.

Pseudohypoparathyroidism type 1b due to paternal uniparental disomy of chromosome 20q.

CONTEXT: Pseudohypoparathyroidism type 1b (PHP1b) is the result of end-organ resistance to PTH and other hormones such as TSH in the absence of any features of Albright's hereditary osteodystrophy. Patients with PHP1b show imprinting abnormalities at the complex GNAS locus. The molecular cause of autosomal dominant familial PHP1b has been well-defined with identification of microdeletions within the GNAS locus or the nearby STX16, but the molecular mechanism of the GNAS imprinting defects in sporadic PHP1b cases remains elusive. OBJECTIVE: We investigated the underlying molecular mechanism of GNAS imprinting defects in two patients with sporadic PHP1b. RESULTS: We identified paternal uniparental disomy of the long arm of chromosome 20 (patUPD20) in two unrelated patients with sporadic PHP1b. This provides an explanation for the patients' GNAS methylation abnormalities and hormone resistance. Our data and a review of the six published cases of patUPD20 suggest that high birth weight and/or early-onset obesity and macrocephaly may also represent features of patUPD20. CONCLUSION: We suggest that patUPD20 should be considered in the evaluation of patients with sporadic PHP1b.

The association between Chiari-like malformation, ventriculomegaly and seizures in cavalier King Charles spaniels.

Cavalier King Charles spaniels (CKCSs) with Chiari-like malformation (CM) and associated seizures are frequently diagnosed with idiopathic epilepsy. There could be an association between ventriculomegaly (V) or caudal fossa overcrowding (CCFP) and seizures. A retrospective case-control study was performed using MRI to investigate the possible association between these morphological abnormalities and seizures. Seizure semiology and, where possible, electroencephalographic (EEG) abnormalities were documented. Eighty-five CKCS with CM were included, 27 with seizures. There was no association between V or CCFP and seizures (P=0.10 and 0.71, respectively). Seizures were classified as having partial onset in 61% of individuals in the study population (95% CI 42.41-76.43%). Another cause of recurrent seizures in CKCS (such as familial epilepsy) is suspected, as previously reported.