Publications by authors named "Bradley Roberts"
Introduction: The field of pharmacogenetics (PGx) is experiencing significant growth, with increasing evidence to support its application in psychiatric care, suggesting its potential to personalize treatment plans, optimize medication efficacy, and reduce adverse drug reactions. However, the perceived utility and practicability of PGx for psychiatric treatment in youth remains underexplored. This study investigated perceived barriers and attitudes in Australian young adults towards the implementation of PGx testing to guide antidepressant treatment in primary care.
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- Astrocytes play crucial and underestimated roles in modulating neuronal circuits, particularly in the striatum, where they regulate dopamine transmission and interact closely with cholinergic interneurons (ChIs).
- The study reveals that striatal astrocytes rapidly excite ChIs and influence dopamine release through nicotinic acetylcholine receptors, operating on very fast timescales.
- A unique anatomical configuration is observed, where ChI somata are closely located to astrocyte somata, allowing for a dynamic interaction that regulates ChI excitability and extracellular calcium, thus impacting overall striatal circuit activity and dopamine signaling.
Introduction: Variation in access to parenteral nutrition (PN) in patients with intestinal failure secondary to malignant bowel obstruction (MBO) exists due to differing practice, beliefs and resource access. We aimed to examine differences in nutritional care pathways and outcomes, by referral to nutrition team for PN in patients with MBO.
Methods: This is a retrospective cohort study of MBO adults admitted to eight UK hospitals within a year and 1 year follow-up.
Article Synopsis
- The study investigates how L-type voltage-gated calcium channels (LTCCs) influence dopamine (DA) release and neuron activity, particularly in relation to Parkinson's disease vulnerability.
- It finds that LTCC function varies significantly between different types of dopamine neurons and is influenced by local biological factors such as sex and specific proteins related to Parkinson's risk.
- The research reveals that factors promoting LTCC activity are linked to increased Parkinsonian risk, while protective factors can inhibit LTCC function, suggesting a complex interaction that may affect the survival of DA neurons in Parkinson's disease.
Article Synopsis
- Pharmacogenetics (PGx) explores how genetic differences among individuals affect their responses to medications, aiming to personalize drug prescriptions beyond the traditional "one-size-fits-all" model.
- In psychiatry, PGx testing has shown promise in enhancing drug effectiveness while minimizing toxicity and adverse reactions, particularly in treating youth mental health conditions.
- Despite supportive evidence from randomized controlled trials, the paper highlights challenges to implementing PGx in clinical practice, focusing on issues specific to youth psychiatry and the need for integrating genetic information to improve mental health treatment.
The Surgeon General's report in the year 2000 highlighted the association between chronic diseases and oral health infections. Current healthcare education programs, regrettably, report only 1 to 3 h of oral health instruction within curricula. In the years 2020-2022, as part of their respective oral health curricula, 278 first-year physician assistant and 12 pre-clinical second-year pharmacy students were invited to participate in a voluntary survey examining the effectiveness of animated succinct, online video-based oral health units.
View Article and Find Full Text PDFAmyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease classified as both a neurodegenerative and neuromuscular disorder. With a complex aetiology and no current cure for ALS, broadening the understanding of disease pathology and therapeutic avenues is required to progress with patient care. Alpha-synuclein (αSyn) is a hallmark for disease in neurodegenerative disorders, such as Parkinson's disease, Lewy body dementia, and multiple system atrophy.
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- The mTOR pathway is crucial for regulating cell growth and metabolism, especially in midbrain dopamine neurons which are sensitive to its signaling.
- This research explores the roles of two mTOR complexes, mTORC1 and mTORC2, in dopamine neurons by creating mice with specific deletions for components of each complex.
- The study finds that blocking mTORC1 significantly disrupts dopamine neuron structure and function, while mTORC2 has subtler effects; however, impairing both leads to major issues in dopamine release, highlighting the need for balanced mTOR signaling for proper dopaminergic function.
Article Synopsis
- Striatal adenosine A receptors (ARs) can inhibit dopamine release, with their activity being regulated by astrocytic equilibrative nucleoside transporter 1 (ENT1), which is sensitive to ethanol.
- In experiments with striatal slices from mice, activating ARs diminished dopamine release, especially at lower stimulation rates, while blocking ARs heightened dopamine release levels, indicating a fundamental tonic inhibition.
- The study found that inhibiting ENT1 increased adenosine levels, further enhancing AR-mediated inhibition, while ethanol reduced adenosine uptake through ENT1, thus promoting dopamine output dynamics and highlighting the complex role of astrocytes in regulating striatal function under the influence of ethanol.
Article Synopsis
- * GABA acts on DA axons through GABA receptors, affecting both the strength of DA release and its short-term plasticity, with specific sources of GABA contributing to this modulation identified.
- * The interaction between GABA and DA signaling might play a key role in psychomotor disorders like Parkinson's disease, suggesting potential new drug targets to regulate DA output.
Article Synopsis
- Striatal dopamine (DA) is essential for regulating action and learning, with recent findings indicating that its release is inhibited by GABA in the striatum.
- The role of plasma membrane GABA uptake transporters (GATs), particularly GAT-1 and GAT-3 located on astrocytes and neurons, in influencing DA output has emerged as a key focus of the research.
- In a mouse model of early parkinsonism, reduced GAT levels lead to increased inhibition of DA release and highlight maladaptive changes affecting DA output in critical regions of the striatum.
Parkinson's disease (PD) affects millions of patients worldwide and is characterized by alpha-synuclein aggregation in dopamine neurons. Molecular tweezers have shown high potential as anti-aggregation agents targeting positively charged residues of proteins undergoing amyloidogenic processes. Here we report that the molecular tweezer CLR01 decreased aggregation and toxicity in induced pluripotent stem cell-derived dopaminergic cultures treated with PD brain protein extracts.
View Article and Find Full Text PDFObjective: Antibiotic stewardship has been recognized as an essential component of dental education. A notable threat to stewardship is the growing trend toward self-medication with nonprescribed antibiotics (SMNPA), particularly among older adults who may be at increased risk for adverse outcomes. This study aimed to assess the need to incorporate SMNPA into dental education by researching (1) professional awareness and (2) self-medication behaviors among older adults.
View Article and Find Full Text PDFPurpose: The 2018 American Dental Education Association Survey of Dental School Seniors showed that 62.5% of graduates felt prepared in practice administration compared to 49.5% in 2013.
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- Mesostriatal dopaminergic neurons have complex branching structures, which influence how action potentials relate to dopamine release in the striatum, a process that’s not yet fully understood.
- This study examines how axonal activity and release probability affect short-term dopamine release using advanced techniques on mouse brain tissue.
- Findings reveal that short-term plasticity in dopamine release is mainly controlled by axonal properties, particularly the dopamine transporter, rather than the initial amount of dopamine released, with distinct behaviors observed in different areas of the dorsal striatum.
Ensemble encoding of action speed by striatal fast-spiking interneurons.
Brain Struct Funct
September 2019
Article Synopsis
- Striatal fast-spiking interneurons (FSIs) strongly inhibit striatal output neurons and play a critical role in action learning through the coordination of their activity.
- Researchers used in vivo calcium imaging and machine learning to study FSIs in mice, investigating how their activity relates to movement.
- The findings indicated that FSIs collectively encode the speed of different action components like walking and head movements, supporting the idea that their dynamics contribute to a model of ensemble inhibition in guiding actions.
Article Synopsis
- The nucleus accumbens is crucial for processing rewards and is mainly made up of medium spiny neurons, where the balance of excitation and inhibition influences its output.
- Research reveals that long-term depression of inhibitory synaptic transmission occurs in this area, which is less understood than excitatory synaptic plasticity.
- The study highlights that this long-term depression is mediated by TrkB receptors and enhanced by ethanol, suggesting that this mechanism could play a role in how ethanol affects reward processing in the brain.
Textbooks, once the standard of education, now have competition when students prefer the Internet and digital technology. The aim of this research study was to survey dental students at one dental school about their use of student-managed Google Docs and other online technologies in collaborative e-learning. All dental students in all four classes at Midwestern University College of Dental Medicine-Arizona were invited to participate in online surveys in 2015 and 2017.
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- The study investigates how glutamatergic projections from the thalamic rostral intralaminar nuclei (rILN) influence dopamine (DA) release and reward-seeking behavior in the dorsal striatum (DS).
- It reveals that activating rILN inputs triggers burst-firing in cholinergic interneurons, affecting D2 receptor activities, which in turn modulates DA-related signaling.
- The research suggests that rILN activation enhances the pursuit of rewards by stimulating striatal cholinergic interneurons, thereby adding complexity to our understanding of how DA release operates in the brain.
Article Synopsis
- Nigrostriatal dopamine (DA) plays an essential role in action selection and learning, and its release is influenced by various striatal neurotransmitters, primarily GABA and cholinergic interneurons (ChIs).
- Research indicates that GABA can directly inhibit DA release in the striatum through GABA receptors, independent of ChI activity, as demonstrated through experiments with male mice striatal slices.
- Findings suggest that GABA and its receptors provide tonic inhibition of DA release, indicating a significant regulatory role for striatal GABA in dopamine signaling.
Background: While fibromyalgia (FM) is characterized by chronic widespread pain and tenderness, its presentation among patients as a continuum of diseases rather than a single disease contributes to the challenges of diagnosis and treatment. The purpose of this analysis was to distinguish and characterize classes of FM within the continuum using data from chronic pain patients.
Methods: FM patients were identified from administrative claims data from the ProCare Systems' network of Michigan pain clinics between January 1999 and February 2015.
Article Synopsis
- Cognitive abilities, such as attention, are controlled by higher brain regions (like the frontal cortex) that manage lower brain structures, but the specific mechanisms involved are not well understood.
- The claustrum, which connects with various cortical areas, is proposed to play a key role in coordinating top-down control, although it's unclear how it processes information from these higher regions.
- Research findings indicate that input from the anterior cingulate cortex (ACC) to the claustrum is essential for effective task performance; this input specifically influences both inhibitory and excitatory neurons within the claustrum, highlighting its importance in directing attention and guiding actions.
Objective: To evaluate the effectiveness of opioids and/or pregabalin on patient-reported outcomes among fibromyalgia (FM) patients based on levels of improvement.
Methods: A total of 1,421 FM patients were identified, with 3,082 observational periods of opioids with or without pregabalin use between April 2008 and February 2015. Patients were categorized by opioids, and pregabalin with and without opioids; opioids were designated by morphine equivalent dose (MED) of ≤ 20 (low MED), > 20 to < 100 (moderate MED), ≥ 100 (high MED), and pregabalin doses of ≤ 150 mg, 151 to 300 mg, and 301 to 450 mg.
Recovery from Acute Illness is dependent on severity of illness. We aimed to investigate whether resilience as the 'ability to bounce back' might also affect recovery. We conducted a scoping review to identify gaps in the existing literature.
View Article and Find Full Text PDFObjective: To compare fibromyalgia (FM) characteristics among patients identified in a community-based chronic pain cohort based on traditional International Classification of Diagnoses 9th revision (ICD-9) diagnostic coding, with that of patients identified using a novel predictive model.
Methods: This retrospective study used data collected from July 1999 to February 17, 2015, in multiple chronic pain clinics in the United States. Patients were assigned to the FM case group based on specific inclusion criteria using ICD-9 codes or, separately, from results of a novel FM predictive model that was developed using random forest and logistic regression techniques.