The discovery of d-cycloserine (), a partial agonist of the NMDA receptor that exhibits antidepressant effects without the psychotomimetic effects of ketamine, has fueled interest in new NMDA-targeting antidepressants. Our objective was to identify potent partial agonists mirroring , particularly tailored for the GluN2B subtype of the NMDA receptor. Through a structure-based drug design approach, we discovered compound .
View Article and Find Full Text PDFAnatomy, the study of human structure, is foundational to medicine. Its language has a long history, with contributions from authors hailing from diverse cultures and countries, adhering to various scientific traditions, speaking different languages, and practicing medicine across a wide gamut of specialties. The resultant disparity in terms provides challenges both for students in learning and for interdisciplinary communication.
View Article and Find Full Text PDFSurgical site infections (SSIs) are healthcare-acquired infections with substantial morbidity. Surgical site infection persist because of low adherence to prevention bundles comprising multiple infection control elements. We propose the "Strike Team" as an implementation strategy to improve adherence and reduce SSI in colorectal surgery.
View Article and Find Full Text PDFThe noradrenaline system attracts attention for its role in mood disorders and neurodegenerative diseases but the lack of well-validated methods impairs our understanding when assessing its function and release in vivo. This study combines simultaneous positron emission tomography (PET) and microdialysis to explore if [C]yohimbine, a selective antagonist radioligand of the α2 adrenoceptors, may be used to assess in vivo changes in synaptic noradrenaline during acute pharmacological challenges. Anesthetised Göttingen minipigs were positioned in a head holder in a PET/CT device.
View Article and Find Full Text PDFBackground: Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease, characterised by fluctuating muscle weakness which makes it challenging to assess symptom severity. Mixed methods psychometrics (MMP), which combines evidence from qualitative research and modern psychometrics, is a versatile approach to the development of patient-centred outcome measures (PCOM) in the context of rare disease. Our objective was to develop the MG Symptom patient-reported outcome (PRO) to assess key aspects of MG severity from the patient perspective.
View Article and Find Full Text PDFThe schizophrenia-associated gene, BRD1, encodes an epigenetic regulator in which chromatin interactome is enriched with genes implicated in mental health. Alterations in histone modifications and epigenetic regulation contribute to brain transcriptomic changes in affective disorders and preclinical data supports a role for BRD1 in psychopathology. However, the implication of BRD1 on affective pathology remains poorly understood.
View Article and Find Full Text PDFThe serotonin transporter (SERT) terminates serotonin signaling by rapid presynaptic reuptake. SERT activity is modulated by antidepressants, e.g.
View Article and Find Full Text PDFThis is a call for action to scientific journals to introduce reporting requirements for toxicity and ecotoxicity studies. Such reporting requirements will support the use of peer-reviewed research studies in regulatory decision-making. Moreover, this could improve the reliability and reproducibility of published studies in general and make better use of the resources spent in research.
View Article and Find Full Text PDF1q21.1 hemizygous microdeletion is a copy number variant leading to eightfold increased risk of schizophrenia. In order to investigate biological alterations induced by this microdeletion, we generated a novel mouse model (Df(h1q21)/+) and characterized it in a broad test battery focusing on schizophrenia-related assays.
View Article and Find Full Text PDFThe antidepressant vortioxetine exerts its effects via modulation of several serotonin (5-HT) receptors and inhibition of the 5-HT transporter (SERT). Additionally, vortioxetine has beneficial effects on aspects of cognitive dysfunction in depressed patients. However, a global examination of the drug effect on brain network connectivity is still missing.
View Article and Find Full Text PDFObjectives: The REDUC clinical study Part B investigated Vacc-4x/rhuGM-CSF therapeutic vaccination prior to HIV latency reversal using romidepsin. The main finding was a statistically significant reduction from baseline in viral reservoir measurements. Here we evaluated HIV-specific functional T-cell responses following Vacc-4x/rhuGM-CSF immunotherapy in relation to virological outcomes on the HIV reservoir.
View Article and Find Full Text PDFBackground: The majority of patients suffering from a whiplash injury will recover, but some will have symptoms (Whiplash Associated Disorders, WAD) for years despite conservative treatment. Some of these patients perceive neck pain that might come from a motion segment, possibly the disc. In comprehensive reviews no evidence has been found that fusion operations have a positive treatment effect on neck pain in WAD patients.
View Article and Find Full Text PDFInterdisciplinary bedside rounds serve as a key mechanism to coordinate patient-centered care. With a focus on optimizing rounds, an interdisciplinary team developed an enhanced, structured process, coined the care team visit. Key findings included improved nurse participation, increased staff collaboration, and decreased Foley catheter days.
View Article and Find Full Text PDFThe measured low frequency vibrational energies of some quantum dots (QDs) deviate from the predictions of traditional elastic continuum models. Recent experiments have revealed that these deviations can be tuned by changing the ligands that passivate the QD surface. This observation has led to speculation that these deviations are due to a mass-loading effect of the surface ligands.
View Article and Find Full Text PDFNeuropharmacology
October 2017
Antagonism of the 5-HT receptor is a promising approach for the symptomatic treatment of Alzheimer's disease (AD). There is compelling preclinical evidence for the procognitive potential of 5-HT receptor antagonists and several compounds are in clinical development, as adjunct therapy to acetylcholinesterase inhibitors (AChEIs). This manuscript summarizes the scientific rationale for the use of 5-HT receptor antagonists as AD treatment, with some focus on the selective and high-affinity 5-HT receptor antagonist idalopirdine (Lu AE58054).
View Article and Find Full Text PDFThis article describes the planning, implementation, and outcomes of 2 complementary quality initiatives, bedside handoff and nurse-initiated interdisciplinary bedside rounds, in a 24-bed medical/surgical intensive care unit. Systematic approaches such as Kotter's change model and unit-based champions were used to redesign care processes and standardize daily communication and workflows. Active partnership with the patient and the family during these changes promoted a strong intensive care unit culture of patient- and family-centered care.
View Article and Find Full Text PDFIdalopirdine (Lu AE58054) is a high affinity and selective antagonist for the human serotonin 5-HT receptor (K 0.83nM) in phase III development for mild-to-moderate Alzheimer's disease as an adjunct therapy to acetylcholinesterase inhibitors (AChEIs). We have studied the effects of idalopirdine on extracellular levels of monoamines, glutamate and acetylcholine in the medial prefrontal cortex (mPFC) of freely-moving rats using microdialysis.
View Article and Find Full Text PDFPrevious studies have shown that partial and full 5-HT receptor agonists reduce antipsychotic-induced catalepsy. Consequently, some antipsychotics combining balanced efficacy between dopamine (DA) D antagonism or partial agonism and 5-HT receptor agonism have a low propensity to induce extrapyramidal side effects (EPS), as reflected by low cataleptogenic activity in rodents. In the present experiments, we attempted to explore the importance of pre- and postsynaptic 5-HT agonistic properties of brexpiprazole and aripiprazole in the context of neurological side-effect liabilities.
View Article and Find Full Text PDFThe goal of the present work was to characterise the effects of selegiline on the rat sleep pattern. Furthermore, for comparative purposes, the pharmacokinetics of selegiline and its metabolites in brain and plasma were investigated, and microdialysis experiments were performed to examine the resulting effect on dopamine, noradrenaline and serotonin levels. Selegiline (1, 5, 10 and 30mg/kg) was found to dose-dependently increase the time spent awake following acute dosing.
View Article and Find Full Text PDFBackground: The schizophrenia-associated BRD1 gene encodes a transcriptional regulator whose comprehensive chromatin interactome is enriched with schizophrenia risk genes. However, the biology underlying the disease association of BRD1 remains speculative.
Methods: This study assessed the transcriptional drive of a schizophrenia-associated BRD1 risk variant in vitro.
We measure the temperature dependence of breathing-mode acoustic vibrations of semiconductor nanocrystals using low-frequency Raman spectroscopy. In CdSe core-only nanocrystals, the lowest-energy l = 0 mode red-shifts with increasing temperature by ∼5% between 77-300 K. Changes to the interatomic bond distances in the inorganic crystal lattice, with corresponding changes to the bulk modulus and density of the material, contribute to the observed energy shift but do not fully explain its magnitude across all nanocrystal sizes.
View Article and Find Full Text PDFRecent experimental and theoretical results have highlighted the surprisingly dominant role of acoustic phonons in regulating dynamic processes in nanocrystals. While it has been known for many years that acoustic phonon frequencies in nanocrystals depend on their size, strategies for tuning acoustic phonon energy at a given fixed size were not available. Here, we show that acoustic phonon frequencies in colloidal quantum dots (QDs) can be tuned through the choice of the surface ligand.
View Article and Find Full Text PDFBackground: Immune priming before reversal of latency might be a component of a functional HIV cure. To assess this concept, we assessed if therapeutic HIV immunisation followed by latency reversal would affect measures of viral transcription, plasma viraemia, and reservoir size in patients with HIV on suppressive antiretroviral therapy.
Methods: In this single-arm, phase 1B/2A trial, we recruited adults treated at the Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark (aged ≥18 years) with successfully treated HIV-1 with plasma RNA loads of less than 50 copies per mL for the previous year and CD4 counts of at least 500 cells per μL.
Major depressive disorder (MDD) is a common psychiatric disorder that often features impairments in cognitive function, and these cognitive symptoms can be important determinants of functional ability. Vortioxetine is a multimodal antidepressant that may improve some aspects of cognitive function in patients with MDD, including attention, processing speed, executive function, and memory. However, the cause of these effects is unclear, and there are several competing theories on the underlying mechanism, notably including regionally-selective downstream enhancement of glutamate neurotransmission and increased acetylcholine (ACh) neurotransmission.
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