Assessing the stability of responding of male mice in the touchscreen 5 choice serial reaction time task: Focus on premature responding.

The five-choice serial reaction time task (5CSRTT) is a test of attention that provides a well-validated ancillary measure of impulsive action, measured by premature responses. The task has been adapted for mice in touchscreen operant boxes, which is thought to offer improved test-retest reliability. Few studies have assessed the long-term stability of performance, including premature responding in this version of the task.

The PRESIDE (PhaRmacogEnomicS In DEpression) Trial: a double-blind randomised controlled trial of pharmacogenomic-informed prescribing of antidepressants on depression outcomes in patients with major depressive disorder in primary care.

Background: The evidence for the clinical utility of pharmacogenomic (PGx) testing is growing, and guidelines exist for the use of PGx testing to inform prescribing of 13 antidepressants. Although previous randomised controlled trials of PGx testing for antidepressant prescribing have shown an association with remission of depression in clinical psychiatric settings, few trials have focused on the primary care setting, where most antidepressant prescribing occurs.

Methods: The PRESIDE Trial is a stratified double-blinded randomised controlled superiority trial that aims to evaluate the impact of a PGx-informed antidepressant prescribing report (compared with standard prescribing using the Australian Therapeutic Guidelines) on depressive symptoms after 12 weeks, when delivered in primary care.

Prenatal and early life factors and type 1 diabetes.

Background: The prevalence of type 1 diabetes is increasing worldwide, suggesting that unknown environmental factors are becoming increasingly important in its pathogenesis.

Aim: The aim of the study was to investigate the possible role of a number of prenatal and perinatal factors in the aetiology of type 1 diabetes.

Methods: Mothers of patients diagnosed with type 1 diabetes (cases) and mothers of children born on the same day and of the same sex as type 1 diabetes patients (controls) were interviewed on a number of prenatal and perinatal factors of interest.

The Therapeutic Alliance with Parents and their Children Working Through a Relational Trauma in the Family.

This study is about how a therapeutic alliance is created and maintained with parents and their children working through a relational trauma. A case study design with narrative analysis as a method of research (Riessman, 2008) and a narrative approach of storying stories, inspired by McCormack (2000), is used. The participants of this study are the parents and their four children, aged between 14 and 5 years, and their systemic therapist.

Why is the Incidence of Type 1 Diabetes Increasing?

Type 1 diabetes is a condition that can lead to serious long-term complications and can have significant psychological and quality of life implications. Its incidence is increasing in all parts of the world, but the reasons for this are incompletely understood. Genetic factors alone cannot explain such a rapid increase in incidence; therefore, environmental factors must be implicated.

Amiodarone-induced type 2 thyrotoxicosis.

The authors present a case of a 55-year-old gentleman with a medical history of atrial fibrillation on amiodarone who presented with weight loss, palpitations and exertional dyspnoea. Thyroid function tests revealed thyrotoxicosis with a free thyroxine (T4) of 117 pmol/L and a thyroid-stimulating hormone (TSH) of <0.008 mIU/L.

Prenatal disruption of D1R-SynGAP complex causes cognitive deficits in adulthood.

γ-aminobutyric acid (GABA)-ergic interneurons are essential for the physiological function of the mammalian central nervous system. Dysregulated GABAergic interneuron function has been implicated in the pathophysiology of a number of neurodevelopmental disorders including schizophrenia and autism spectrum disorder. Tangential migration is an important process to ensure the proper localization of GABAergic interneurons.

Clozapine reliably increases the motivation for food: parsing the role of the 5-HT and H receptors.

Rationale And Objectives: Although clozapine is effective in treating schizophrenia, it is associated with adverse side effects including weight gain and metabolic syndrome. Despite this, the role of clozapine on feeding behaviour and food intake has not been thoroughly characterised. Clozapine has a broad pharmacological profile, with affinities for several neurotransmitter receptors, including serotonin (5-hydroxytriptamine, 5-HT) and histamine.

Disruption of SynGAP-dopamine D1 receptor complexes alters actin and microtubule dynamics and impairs GABAergic interneuron migration.

Disruption of γ-aminobutyric acid (GABA)-ergic interneuron migration is implicated in various neurodevelopmental disorders, including autism spectrum disorder and schizophrenia. The dopamine D1 receptor (D1R) promotes GABAergic interneuron migration, which is disrupted in various neurological disorders, some of which are also associated with mutations in the gene encoding synaptic Ras-guanosine triphosphatase-activating protein (SynGAP). Here, we explored the mechanisms underlying these associations and their possible connection.

Identification of an p.Gly292fs Frameshift Mutation Presenting as Diabetes During Pregnancy in a Maltese Family.

The diagnosis of maturity onset diabetes of the young (MODY) is a challenging process in view of the extensive clinical and genetic heterogeneity of the disease. Mutations in the gene encoding hepatocyte nuclear factor 1α () are responsible for most forms of monogenic diabetes in Northern European populations. Genetic analysis through a combination of whole exome sequencing and Sanger sequencing in three Maltese siblings and their father identified a rare duplication/frameshift mutation in exon 4 of that lies within a known mutational hotspot in this gene.

Adolescent exposure to Δ9-tetrahydrocannabinol delays acquisition of paired-associates learning in adulthood.

Rationale And Objectives: Adolescence is a sensitive period of brain development, during which there may be a heightened vulnerability to the effects of drug use. Despite this, the long-term effects of cannabis use during this developmental period on cognition are poorly understood.

Methods: We exposed adolescent rats to escalating doses of Δ9-tetrahydrocannabinol (THC)-the primary psychoactive component of cannabis-or vehicle solution during postnatal days (PND) 35-45, a period of development that is analogous to human adolescence (THC doses: PND 35-37, 2.

Characteristics of children with refractory acute otitis media treated at the pediatric emergency department.

Introduction: Refractory acute otitis media (rAOM) is defined as the persistence of signs and symptoms of AOM for more than 48 to 72 hours after the initiation of antibiotic treatment. These patients are often referred to the pediatric emergency department (PED). We sought to study rAOM cases referred to our PED, and to evaluate their clinical characteristics and response to our local management guidelines.

Dorsal raphe serotonin neurons inhibit operant responding for reward via inputs to the ventral tegmental area but not the nucleus accumbens: evidence from studies combining optogenetic stimulation and serotonin reuptake inhibition.

The monoamine neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) exerts an inhibitory influence over motivation, but the circuits mediating this are unknown. Here, we used an optogenetic approach to isolate the contribution of dorsal raphe nucleus (DRN) 5-HT neurons and 5-HT innervation of the mesolimbic dopamine (DA) system to motivated behavior in mice. We found that optogenetic stimulation of DRN 5-HT neurons enhanced downstream 5-HT release, but this was not sufficient to inhibit operant responding for saccharin, a measure of motivated behavior.

Persistent sleep disordered breathing after adenoidectomy and/or tonsillectomy: a long-term survey in a tertiary pediatric hospital.

Purpose: To determine the long-term prevalence of persistent sleep disordered breathing (SDB) in children, after adenoidectomy, tonsillectomy or adenotonsillectomy, and to assess the relationship between baseline characteristics and persistent nocturnal symptoms.

Methods: The clinical charts of children operated for adenoidectomy and/or tonsillectomy in a tertiary hospital, between January 2000 and March 2016, were retrospectively reviewed. All patients who had signs of SDB prior to surgery received a six-question validated pediatric questionnaire, the Hierarchic Severity Clinical Scale (HSCS).

Incidence of type 1 diabetes and distance from the sea: A descriptive epidemiological study.

Background: Increasingly, environmental factors are being shown to play a role in the etiology of type 1 diabetes (T1D). One geographical feature that exerts a major effect on climate but whose relationship with T1D incidence has not been studied is distance from the sea. This study investigated any possible relationship between distance from the sea and the incidence of T1D.

Effects of acute olanzapine exposure on central insulin-mediated regulation of whole body fuel selection and feeding.

The use of antipsychotics is associated with severe disruptions in whole body glucose and lipid metabolism which may in part occur through the central nervous system and impaired insulin action at the brain. Here we investigated whether olanzapine treatment might also affect the ability of central insulin treatment to regulate food intake and fuel preference in the light and dark cycle. Male Sprague-Dawley rats were treated with olanzapine (or vehicle solution; 3 mg/kg, subcutaneous) and a simultaneous acute intracerebral ventricular (ICV) infusion of insulin (or vehicle; 3 μL at 10mU; ICV) at the beginning of the 12-h light and dark cycles.

Clozapine reduces nicotine self-administration, blunts reinstatement of nicotine-seeking but increases responding for food.

People with schizophrenia display significantly higher rates of smoking than the general population, which may be due to an interaction between nicotine and antipsychotic medication. While the conventional antipsychotic drug haloperidol sometimes increases cigarette smoking in patients with schizophrenia, there is some evidence suggesting that clozapine, an atypical antipsychotic drug, may reduce nicotine use in these patients. However, the effects of antipsychotic drugs like clozapine on aspects of nicotine self-administration and reinstatement have not been systematically examined.

Enantioselective Chemical Syntheses of the Furanosteroids (-)-Viridin and (-)-Viridiol.

Herein we describe concise enantioselective chemical syntheses of (-)-viridin and (-)-viridiol. Our convergent approach couples two achiral fragments of similar complexity and employs an enantioselective intramolecular Heck reaction to set the absolute stereochemical configuration of an all-carbon quaternary stereocenter. To complete the syntheses of these base- and nucleophile-sensitive natural products, we conduct carefully orchestrated site- and diastereoselective oxidations and other transformations.

Cationic Pd(II)-catalyzed C-H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies.

Cationic palladium(II) complexes have been found to be highly reactive towards aromatic C-H activation of arylureas at room temperature. A commercially available catalyst [Pd(MeCN)4](BF4)2 or a nitrile-free cationic palladium(II) complex generated in situ from the reaction of Pd(OAc)2 and HBF4, effectively catalyzes C-H activation/cross-coupling reactions between aryl iodides, arylboronic acids and acrylates under milder conditions than those previously reported. The nature of the directing group was found to be critical for achieving room temperature conditions, with the urea moiety the most effective in promoting facile coupling reactions at an ortho C-H position.

Midline thalamic reuniens lesions improve executive behaviors.

The role of the thalamus in complex cognitive behavior is a topic of increasing interest. Here we demonstrate that lesions of the nucleus reuniens (NRe), a midline thalamic nucleus interconnected with both hippocampal and prefrontal circuitry, lead to enhancement of executive behaviors typically associated with the prefrontal cortex. Rats were tested on four behavioral tasks: (1) the combined attention-memory (CAM) task, which simultaneously assessed attention to a visual target and memory for that target over a variable delay; (2) spatial memory using a radial arm maze, (3) discrimination and reversal learning using a touchscreen operant platform, and (4) decision-making with delayed outcomes.

Intraneuronal Amyloid Beta Accumulation Disrupts Hippocampal CRTC1-Dependent Gene Expression and Cognitive Function in a Rat Model of Alzheimer Disease.

In Alzheimer disease (AD), the accumulation of amyloid beta (Aβ) begins decades before cognitive symptoms and progresses from intraneuronal material to extracellular plaques. To date, however, the precise mechanism by which the early buildup of Aβ peptides leads to cognitive dysfunction remains unknown. Here, we investigate the impact of the early Aβ accumulation on temporal and frontal lobe dysfunction.

Hippocampal interplay with the nucleus accumbens is critical for decisions about time.

Human cognition depends upon the capacity to make decisions in the present that bear upon outcomes in the future. The nucleus accumbens, a recipient of direct projections from both the hippocampus and orbitofrontal cortex, is known to contribute to these aspects of decision-making. Here we demonstrate that interaction of the nucleus accumbens with the hippocampus, but not the orbitofrontal cortex, is critical in shaping decisions that involve time trade-offs.