Changes and persistence in heart rate variability before and during social stress: A comparison of individuals with and without social anxiety disorder.

Individuals with social anxiety disorder (SAD) experience significant and persistent fear of social situations as they anticipate rejection, scrutiny, and embarrassment. Given that physiological reactions to social situations may shape emotional experience in SAD, understanding psychophysiological changes operating in SAD may be important to address this potentially key perpetuating factor. This study compared the patterns of change (via contrasts of estimated marginal means) and persistence (via autoregressive models) of two indices of heart rate variability (HRV; Root Mean Square of Successive Differences between normal heartbeats, and High-Frequency absolute units) as physiological measures of emotion regulation, between individuals with SAD (n = 94) and without (n = 59) using the Trier Social Stress Test phases (TSST).

Treatment consistent with idiopathic multicentric Castleman disease guidelines is associated with improved outcomes.

Idiopathic multicentric Castleman disease (iMCD) is a rare hematologic disorder with an unknown etiology. Clinical presentation is heterogeneous, ranging from mild constitutional symptoms with lymphadenopathy to life-threatening multiorgan dysfunction. International, consensus treatment guidelines developed in 2018 relied upon a limited number of clinical trials and small case series; however, to our knowledge, real-world performance of these recommendations has not been subsequently studied.

An Industry Survey on Managing the Pharmacovigilance System Master File in a Global Environment: The Need for a Pragmatic Approach.

Background: Legislative requirements for Marketing Authorisation Holders (MAHs) to maintain a Pharmacovigilance System Master File (PSMF) were introduced in the European Union (EU) in 2010, operationalised in 2012 and subsequently introduced in other territories. There are no internationally agreed standards for the PSMF and country/regional requirements vary, leaving room for interpretation. This creates complexities for MAHs in implementing and maintaining multiple PSMFs.

A previously unappreciated polymorphism in the beta chain of I-A expressed in autoimmunity-prone SJL mice: Combined impact on antibody, CD4 T cell recognition and MHC class II dimer structural stability.

In the process of structure-function studies on the MHC class II molecule expressed in autoimmunity prone SJL mice, I-A, we discovered a disparity from the reported sequence of the MHC class II beta chain. The variant is localized at a highly conserved site of the beta chain, at residue 58. Our studies revealed that this single amino acid substitution of Pro for Ala at this residue, found in I-A, changes the structure of the MHC class II molecule, as evidenced by a loss of recognition by two monoclonal antibodies, and elements of MHC class II conformational stability identified through molecular dynamics simulation.

Knowledge of biosimilars and perceptions of the naming conventions for biosimilar products in clinical practice in the United States.

Background: Biosimilar therapies and their naming conventions are both relatively new to the drug development market and in clinical practice. We studied the use of the four-letter naming convention in practice and the knowledge, perceptions, and preferences of US health care providers.

Methods: A survey was distributed among health care professionals with a history of utilizing biosimilars in clinical practice to measure key knowledge and the presence of discernable naming trends.

Oestrogen treatment modulates the impact of cognitive experience and task complexity on memory in middle-aged surgically menopausal rats.

Menopause has been linked to changes in memory. Oestrogen-containing hormone therapy is prescribed to treat menopause-related symptoms and can ameliorate memory changes, although the parameters impacting oestrogen-related memory efficacy are unclear. Cognitive experience and practice have been shown to be neuroprotective and to improve learning and memory during ageing, with the type of task playing a role in subsequent cognitive outcomes.

Vaccination reshapes the virus-specific T cell repertoire in unexposed adults.

We examined how baseline CD4 T cell repertoire and precursor states impact responses to pathogen infection in humans using primary immunization with yellow fever virus (YFV) vaccine. YFV-specific T cells in unexposed individuals were identified by peptide-MHC tetramer staining and tracked pre- and post-vaccination by tetramers and TCR sequencing. A substantial number of YFV-reactive T cells expressed memory phenotype markers and contained expanded clones in the absence of exposure to YFV.

Sol-gel synthesis of 2-dimensional TiO: self-assembly of Ti-oxoalkoxy-acetate complexes by carboxylate ligand directed condensation.

2-Dimensional (2D) metal oxides have many potential industrial applications including heterogeneous catalysis, water splitting, renewable energy conversion, supercapacitor applications, biomaterials, gas separation and gas storage. Herein we report a simple and scalable method for the preparation of 2D TiO nanostructures by reaction of titanium isopropoxide with acetic acid at 333 K in isopropanol, followed by calcination at 673 K to remove the organic ligands. Both the products and reaction intermediates have been studied using electron microscopy, X-ray diffraction, N physisorption, nuclear magnetic resonance, thermogravimetric analysis, and X-ray photoelectron, Raman, and infrared spectroscopy.

The patient's view on rare disease trial design - a qualitative study.

Background: Clinical trials in rare diseases are more challenging than trials in frequent diseases. Small numbers of eligible trial participants, often complicated by heterogeneity among rare disease patients, hamper the design and conduct of a 'classical' Randomized Controlled Trial. Therefore, novel designs are developed by statisticians.

Mortality in patients with Sanfilippo syndrome.

Background: Sanfilippo syndrome (mucopolysaccharidosis type III; MPS III) is an inherited monogenic lysosomal storage disorder divided into subtypes A, B, C and D. Each subtype is characterized by deficiency of a different enzyme participating in metabolism of heparan sulphate. The resultant accumulation of this substrate in bodily tissues causes various malfunctions of organs, ultimately leading to premature death.

Recommendations on clinical trial design for treatment of Mucopolysaccharidosis Type III.

Background: Mucopolysaccharidosis type III is a progressive, neurodegenerative lysosomal storage disorder for which there is currently no effective therapy. Though numerous potential therapies are in development, there are several challenges to conducting clinical research in this area. We seek to make recommendations on the approach to clinical research in MPS III, including the selection of outcome measures and trial endpoints, in order to improve the quality and impact of research in this area.

Benefits of Hormone Therapy Estrogens Depend on Estrogen Type: 17β-Estradiol and Conjugated Equine Estrogens Have Differential Effects on Cognitive, Anxiety-Like, and Depressive-Like Behaviors and Increase Tryptophan Hydroxylase-2 mRNA Levels in Dorsal Raphe Nucleus Subregions.

Decreased serotonin (5-HT) function is associated with numerous cognitive and affective disorders. Women are more vulnerable to these disorders and have a lower rate of 5-HT synthesis than men. Serotonergic neurons in the dorsal raphe nucleus (DRN) are a major source of 5-HT in the forebrain and play a critical role in regulation of stress-related disorders.

The diagnostic journey of patients with mucopolysaccharidosis I: A real-world survey of patient and physician experiences.

Unlabelled: Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disease. Affected individuals have disease ranging from attenuated to severe with significant disease burden, disability, and premature death. Early treatment with enzyme replacement therapy and/or stem cell transplantation can reduce disease progression and improve outcomes.

miR-34a(-/-) mice are susceptible to diet-induced obesity.

Objective: MicroRNA (miR)-34a regulates inflammatory pathways, and increased transcripts have been observed in serum and subcutaneous adipose of subjects who have obesity and type 2 diabetes. Therefore, the role of miR-34a in adipose tissue inflammation and lipid metabolism in murine diet-induced obesity was investigated.

Methods: Wild-type (WT) and miR-34a(-/-) mice were fed chow or high-fat diet (HFD) for 24 weeks.

A comparison of progestins within three classes: Differential effects on learning and memory in the aging surgically menopausal rat.

Introduction: For decades, progestins have been included in hormone therapies (HT) prescribed to women to offset the risk of unopposed estrogen-induced endometrial hyperplasia. However, the potential effects on cognition of subcategories of clinically used progestins have been largely unexplored.

Methods: In two studies, the present investigation evaluated the cognitive effects of norethindrone acetate (NETA), levonorgestrel (LEVO), and medroxyprogesterone acetate (MPA) on the water radial-arm maze (WRAM) and Morris water maze (MM) in middle-aged ovariectomized rats.

Long-Term Cognitive and Functional Outcomes in Children with Mucopolysaccharidosis (MPS)-IH (Hurler Syndrome) Treated with Hematopoietic Cell Transplantation.

The long-term cognitive and functional outcomes of children with mucopolysaccharidosis type I (MPS-IH) post-hematopoietic cell transplant (HCT) are not well documented, and the role of genetic and treatment factors in these outcomes has yet to be defined. In this multi-site, international study, we (1) characterize the cognitive and functional status of 47 individuals (ages 2-25, mean of 10.6 years) with MPS-IH who are 1-24 years post HCT (mean = 9 years) and (2) examine contributions of genotype, transplant characteristics, and sociodemographic factors to cognitive ability, adaptive behavior, and quality of life.

Diversification of edaravone via palladium-catalyzed hydrazine cross-coupling: Applications against protein misfolding and oligomerization of beta-amyloid.

N-Aryl derivatives of edaravone were identified as potentially effective small molecule inhibitors of tau and beta-amyloid aggregation in the context of developing disease-modifying therapeutics for Alzheimer's disease (AD). Palladium-catalyzed hydrazine monoarylation protocols were then employed as an expedient means of preparing a focused library of 21 edaravone derivatives featuring varied N-aryl substitution, thereby enabling structure-activity relationship (SAR) studies. On the basis of data obtained from two functional biochemical assays examining the effect of edaravone derivatives on both fibril and oligomer formation, it was determined that derivatives featuring an N-biaryl motif were four-fold more potent than edaravone.

The GABAA antagonist bicuculline attenuates progesterone-induced memory impairments in middle-aged ovariectomized rats.

In women, high levels of natural progesterone have been associated with detrimental cognitive effects via the "maternal amnesia" phenomenon as well as in controlled experiments. In aged ovariectomized (Ovx) rats, progesterone has been shown to impair cognition and impact the GABAergic system in cognitive brain regions. Here, we tested whether the GABAergic system is a mechanism of progesterone's detrimental cognitive effects in the Ovx rat by attempting to reverse progesterone-induced impairments via concomitant treatment with the GABAA antagonist, bicuculline.

Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus document.

Introduction: Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory.

Navigating to new frontiers in behavioral neuroscience: traditional neuropsychological tests predict human performance on a rodent-inspired radial-arm maze.

We constructed an 11-arm, walk-through, human radial-arm maze (HRAM) as a translational instrument to compare existing methodology in the areas of rodent and human learning and memory research. The HRAM, utilized here, serves as an intermediary test between the classic rat radial-arm maze (RAM) and standard human neuropsychological and cognitive tests. We show that the HRAM is a useful instrument to examine working memory ability, explore the relationships between rodent and human memory and cognition models, and evaluate factors that contribute to human navigational ability.

Mortality in patients with morquio syndrome a.

Background: Morquio syndrome A (mucopolysaccharidosis type IVA) is an autosomal recessive, life-limiting lysosomal storage disease characterized by deficient activity of the enzyme galactosamine-6-sulfatase. The disease affects multiple body systems, and patients require multidisciplinary care from an early age.

Methods: To better understand the natural progression of the disease, life expectancy and common causes of death, death certificates were evaluated for 27 patients (15 male, 12 female) with Morquio syndrome A in the UK, covering the years 1975-2010.