Esmethadone (REL-1017) and Other Uncompetitive NMDAR Channel Blockers May Improve Mood Disorders via Modulation of Synaptic Kinase-Mediated Signaling.

This article presents a mechanism of action hypothesis to explain the rapid antidepressant effects of esmethadone (REL-1017) and other uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonists and presents a corresponding mechanism of disease hypothesis for major depressive disorder (MDD). Esmethadone and other uncompetitive NMDAR antagonists may restore physiological neural plasticity in animal models of depressive-like behavior and in patients with MDD via preferential tonic block of pathologically hyperactive GluN2D subtypes. Tonic Ca currents via GluN2D subtypes regulate the homeostatic availability of synaptic proteins.

The Genomic Architecture of Pregnancy-Associated Plasticity in the Maternal Mouse Hippocampus.

Pregnancy is associated with extraordinary plasticity in the maternal brain. Studies in humans and other mammals suggest extensive structural and functional remodeling of the female brain during and after pregnancy. However, we understand remarkably little about the molecular underpinnings of this natural phenomenon.

Variations in age structure and growth in congeners Lacerta viridis and Lacerta media.

Determining the age of any species allows it to be analyzed from the ontogenetic, demographic, and ecological perspectives. In the present study, we tested the hypothesis that the age structure of congener species (Lacerta media and Lacerta viridis) with the same ecological niche may vary in different areas. In this context, we applied skeletochronology method to reveal various demographic parameters, such as age structure, longevity, age at sexual maturity, growth rate, survival rate, adult life expectancy, and the relationship between age and body size in the green lizard, L.

REL-1017 (Esmethadone) as Adjunctive Treatment in Patients With Major Depressive Disorder: A Phase 2a Randomized Double-Blind Trial.

The purpose of this study was to examine the effects of REL-1017 (esmethadone), a novel -methyl-d-aspartate receptor (NMDAR) channel blocker, in patients with major depressive disorder who failed to benefit from one to three standard antidepressant treatments in their current major depressive episode. A 7-day phase 2 multicenter randomized double-blind placebo-controlled trial, comprising three arms, was conducted to assess the safety, tolerability, pharmacokinetics, and efficacy of two dosages of REL-1017 (25 mg or 50 mg orally once a day). Patients were randomly assigned in a 1:1:1 ratio to placebo (N=22), REL-1017 25 mg/day (N=19), or REL-1017 50 mg/day (N=21).

Defect-induced BC electrodes for high energy density supercapacitor devices.

Boron carbide powders were synthesized by mechanically activated annealing process using anhydrous boron oxide (BO) and varying carbon (C) sources such as graphite and activated carbon: The precursors were mechanically activated for different times in a high energy ball mill and reacted in an induction furnace. According to the Raman analyses of the carbon sources, the I(D)/I(G) ratio increased from ~ 0.25 to ~ 0.

Adherence to guidelines on nutrition support during intensive treatment of acute myeloid leukemia patients: A nationwide comparison.

Background & Aims: The level of adherence to the updated guidelines of The European Societies for Clinical Nutrition and Metabolism (ESPEN) and for Blood and Marrow Transplantation (EBMT) on nutrition in intensively treated adult acute myeloid leukemia (AML) patients in clinical practice is unknown. The aim of this nationwide survey was to investigate ESPEN/EBMT nutritional guideline adherence during intensive AML treatment, variation in nutrition support practices among hospitals and whether these practices changed after guideline publication.

Methods: All 22 Dutch hospitals providing (aftercare following) high-dose chemotherapy and/or hematopoietic stem cell transplantation for adult AML patients were surveyed on nutrition support practices during these intensive AML treatments.

LiMgCoBO as a positive electrode material for Li-ion batteries.

LiCoBO could be a promising cathode material given the electronic and ionic conductivity problems are addressed. Here, Mg substitution in LiCoBO is employed to stabilise the structure and improve the electrochemical performance. LiMgCoBO is synthesised for the first time sol-gel method and Mg substitution in the structure is verified by X-ray powder diffraction and energy dispersive X-ray analyses.

ZNHIT3 is defective in PEHO syndrome, a severe encephalopathy with cerebellar granule neuron loss.

Progressive encephalopathy with oedema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is an early childhood onset, severe autosomal recessive encephalopathy characterized by extreme cerebellar atrophy due to almost total granule neuron loss. By combining homozygosity mapping in Finnish families with Sanger sequencing of positional candidate genes and with exome sequencing a homozygous missense substitution of leucine for serine at codon 31 in ZNHIT3 was identified as the primary cause of PEHO syndrome. ZNHIT3 encodes a nuclear zinc finger protein previously implicated in transcriptional regulation and in small nucleolar ribonucleoprotein particle assembly and thus possibly to pre-ribosomal RNA processing.

Improvement in the transport critical current density and microstructure of isotopic MgB monofilament wires by optimizing the sintering temperature.

Superconducting wires are widely used in fabricating magnetic coils in fusion reactors. In consideration of the stability of B against neutron irradiation and lower induced radio-activation properties, MgB superconductor with B serving as boron source is an alternative candidate to be used in fusion reactor with severe irradiation environment. In present work, a batch of monofilament isotopic MgB wires with amorphous B powder as precursor were fabricated using powder-in-tube (PIT) process at different sintering temperature, and the evolution of their microstructure and corresponding superconducting properties was systemically investigated.

Improved Superconducting properties in the Mg(11)B2 low activation superconductor prepared by low-temperature sintering.

Mg(11)B2 has a great application prospect in the superconducting coils for fusion reactor as the "low activation superconductors". The un-doped Mg(11)B2 and Cu-doped Mg(11)B2 bulks using (11)B as a boron precursor were fabricated by low-temperature sintering in present work. It was found that the prepared Mg(11)B2 low activation superconductors exhibit better Jc performance than all of other Mg(11)B2 samples reported in previous studies.

Dysfunctional ADAM22 implicated in progressive encephalopathy with cortical atrophy and epilepsy.

Objective: To identify the molecular genetic basis of a syndrome characterized by rapidly progressing cerebral atrophy, intractable seizures, and intellectual disability.

Methods: We performed exome sequencing in the proband and whole-genome single nucleotide polymorphism genotyping (copy number variant analysis) in the proband-parent trio. We used heterologous expression systems to study the functional consequences of identified mutations.

Opioid Modulation With Buprenorphine/Samidorphan as Adjunctive Treatment for Inadequate Response to Antidepressants: A Randomized Double-Blind Placebo-Controlled Trial.

Objective: Major depressive disorder has been associated with dysregulation of the endogenous opioid system. The authors sought to determine whether opioid modulation achieved through administration of ALKS 5461, a combination of a μ- and κ-opioid partial agonist, buprenorphine, and a μ-opioid antagonist, samidorphan, would exhibit antidepressant activity in patients with major depression.

Method: A multicenter, randomized, double-blind, placebo-controlled, two-stage sequential parallel comparison design study was conducted in adults with major depression who had an inadequate response to one or two courses of antidepressant treatment.

Report from AmSECT's International Consortium for Evidence- Based Perfusion Consensus Statement: Minimal Criteria for Reporting Cardiopulmonary Bypass-Related Contributions to Red Blood Cell Transfusions Associated With Adult Cardiac Surgery.

Gaps remain in our understanding of the contribution of bypass-related practices associated with red blood cell (RBC) transfusions after cardiac surgery. Variability exists in the reporting of bypass-related practices in the peer-reviewed literature. In an effort to create uniformity in reporting, a draft statement outlining proposed minimal criteria for reporting cardiopulmonary bypass (CPB)- related contributions (i.

Selenoprotein biosynthesis defect causes progressive encephalopathy with elevated lactate.

Objective: We aimed to decipher the molecular genetic basis of disease in a cohort of children with a uniform clinical presentation of neonatal irritability, spastic or dystonic quadriplegia, virtually absent psychomotor development, axonal neuropathy, and elevated blood/CSF lactate.

Methods: We performed whole-exome sequencing of blood DNA from the index patients. Detected compound heterozygous mutations were confirmed by Sanger sequencing.

[Exome sequencing revealed Allan-Herndon-Dudley syndrome underlying multiple disabilities].

Normal function of the thyroid gland is the cornerstone of a child's mental development and physical growth. We describe a Finnish family, in which the diagnosis of three brothers became clear after investigations that lasted for more than 30 years. Two of the sons have already died.

Variants in CUL4B are associated with cerebral malformations.

Variants in cullin 4B (CUL4B) are a known cause of syndromic X-linked intellectual disability. Here, we describe an additional 25 patients from 11 families with variants in CUL4B. We identified nine different novel variants in these families and confirmed the pathogenicity of all nontruncating variants.

X-exome sequencing in Finnish families with intellectual disability--four novel mutations and two novel syndromic phenotypes.

Background: X-linked intellectual disability (XLID) is a group of genetically heterogeneous disorders characterized by substantial impairment in cognitive abilities, social and behavioral adaptive skills. Next generation sequencing technologies have become a powerful approach for identifying molecular gene mutations relevant for diagnosis.

Methods & Objectives: Enrichment of X-chromosome specific exons and massively parallel sequencing was performed for identifying the causative mutations in 14 Finnish families, each of them having several males affected with intellectual disability of unknown cause.

Dominant GDAP1 founder mutation is a common cause of axonal Charcot-Marie-Tooth disease in Finland.

We describe a founder mutation in the gene encoding ganglioside-induced differentiation associated-protein 1 (GDAP1), leading to amino acid change p.H123R, as a common cause of autosomal dominant axonal Charcot-Marie-Tooth (CMT2) neuropathy in Finland. The mutation explains up to 14 % of CMT2 in Finland, where most patients with axonal neuropathy have remained without molecular diagnosis.

A microduplication on chromosome 17p13.1p13.3 including the PAFAH1B1 (LIS1) gene.

Recently, three children with a microduplication in 17p13 including the PAFAH1B1 gene that encodes LIS1 were reported. LIS1 overexpression has earlier been shown to affect brain development by causing migrational defects and reductions in brain volume [Bi et al., 2009].

Defect structure in aliovalently-doped and isovalently-substituted PbTiO3 nano-powders.

The defect structure of Fe(3+)-, Cu(2+)-, Mn(4+)- and Gd(3+)-doped PbTiO(3) nano-powders has been studied by electron paramagnetic resonance (EPR) spectroscopy. Analogous to the situation for 'bulk' ferroelectrics, Fe(3+) and Cu(2+) act as acceptor-type functional centers that form defect complexes with charge-compensating oxygen vacancies. The corresponding defect dipoles are aligned along the direction of spontaneous polarization, P(S), and possess an additional defect polarization, P(D).

A new distal myopathy with mutation in anoctamin 5.

We have been following clinically and with muscle MRI for the past 3-decades a Finnish family with two patients with distal muscular dystrophy. Previously we demonstrated the cellular defect in these patients to be defective membrane repair and more recently have identified the causative gene to be anoctamin 5 (ANO5). The disorder seen in these patients is characterized by onset in the third decade.

[Treatment of cleft lip and palate in Finland].

In Finland about 120 babies are born with cleft lip and palate per year. The largest group is those with isolated cleft palate (60%) and only one fourth have complete cleft lip and palate. The clefts are closed under one year of age.

Low density lipoprotein receptor-related protein 5 (LRP5) mutations and osteoporosis, impaired glucose metabolism and hypercholesterolaemia.

Objective: Mutations in the low-density lipoprotein receptor-related protein 5 gene (LRP5) underlie osteoporosis-pseudoglioma syndrome. Animal models implicate a role for LRP5 in lipid and glucose homeostasis. The objective was to evaluate metabolic consequences of LRP5 mutations in humans.