Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Neuroscience Institute
Total Results:
13474
Switching to e-cigarettes as harm reduction among individuals with chronic disease who currently smoke: Results of a pilot randomized controlled trial
INTRODUCTION/BACKGROUND:E-cigarettes (ECs) may be an effective harm reduction strategy for individuals with conditions like chronic obstructive pulmonary disease (COPD), asthma, coronary artery disease (CAD), and peripheral arterial disease (PAD) who smoke combustible cigarettes (CCs). Our aim was to examine how individuals with chronic conditions transition from CCs to ECs and its impact on health outcomes. METHODS:In a pilot randomized controlled trial (RCT), patients with COPD, asthma, CAD/PAD who currently smoke CCs and have not used nicotine replacement therapy (NRT) or ECs in the past 14 days were randomized to receive ECs or combination NRT with behavioral counselling. Disease symptoms, acceptability/satisfaction (TSQM-9) and feasibility, and cigarettes per day (CPD), and/or EC use were collected at baseline, 3-, and 6-months. Descriptive statistics and a linear regression were conducted to explore changes in CPD and chronic condition-specific assessments (CAT, SAQ-7, ACT) that assess COPD, asthma, and CAD/PAD symptom change. RESULTS:At 3-months, the EC group (n=63, mean CPD=9±11) reduced their CPD by 54% vs. 60% in the NRT group (n=58, mean CPD=7±6), p=0.56. At 6-months, 17.5% had switched completely to ECs while 23% quit smoking in the NRT arm. CAT scores showed a significant 6-point reduction in the EC arm (p=0.03). Participants scored an average of 69±27 for EC effectiveness, 87±23 for convenience, and 75±27 for overall satisfaction. CONCLUSIONS:This pilot study suggests that ECs may be a safer alternative for chronic condition patients using CCs and warrants further research on expected smoking cessation/reduction among individuals who use ECs. IMPLICATIONS/CONCLUSIONS:The findings from this pilot RCT hold significant implications with chronic conditions such as COPD, asthma, CAD and PAD who smoke CCs. The observed reduction in cigarettes per day and improvement in respiratory symptoms suggest that switching to ECs appears feasible and acceptable among those with chronic diseases. These results suggest that ECs may offer an alternative for individuals struggling to quit CC smoking through existing pharmacotherapies. This study supports further exploration of switching to ECs as a harm reduction strategy among CC users who have been unsuccessful at quitting by other means.
PMID: 38995184
ISSN: 1469-994x
CID: 5732502
Transsynaptic modulation of cerebellar nuclear cells: theta AC-burst stimulation
PMCID:11638969
PMID: 39637565
ISSN: 1741-2552
CID: 5762182
Dopamine neuron dysfunction and loss in the PrknR275W mouse model of juvenile parkinsonism
Mutations in the PRKN gene encoding the protein parkin cause autosomal recessive juvenile parkinsonism (ARJP). Harnessing this mutation to create an early-onset Parkinson's disease mouse model would provide a unique opportunity to clarify the mechanisms involved in the neurodegenerative process and lay the groundwork for the development of neuroprotective strategies. To this end, we created a knock-in mouse carrying the homozygous PrknR275W mutation, which is the missense mutation with the highest allelic frequency in PRKN patients. We evaluated the anatomical and functional integrity of the nigrostriatal dopamine (DA) pathway, as well as motor behaviour in PrknR275W mice of both sexes. We report here that PrknR275W mice show early DA neuron dysfunction, age-dependent loss of DA neurons in the substantia nigra, decreased DA content and stimulus-evoked DA release in the striatum, and progressive motor impairment. Together, these data show that the PrknR275W mouse recapitulates key features of ARJP. Thus, these studies fill a critical need in the field by introducing a promising new Parkinson's disease model in which to study causative mechanisms of the disease and test therapeutic strategies.
PMID: 39350737
ISSN: 1460-2156
CID: 5762092
AI is a viable alternative to high throughput screening: a 318-target study
High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery.
SCOPUS:85191821387
ISSN: 2045-2322
CID: 5658952
Professor Alessandro Zuddas' Impact and Legacy: The Influential Networking and Human Connection Skills of a Passionate Scientist, Clinical Academic, and Pioneer in Child and Adolescent Psychopharmacology
Professor Alessandro Zuddas, from the University of Cagliari (Italy), passed away prematurely in July 2022. As a prominent figure in child and adolescent neuropsychiatry, he substantially influenced the fields of neurodevelopmental disorders and neuropsychopharmacology both nationally and internationally. Professor Zuddas was a renowned expert in basic and clinical research in child and adolescent psychopharmacology, an enlightened and stimulating educator, and a mentor to many students, residents, and senior colleagues. With his enthusiasm and unique ability to network, he contributed enormously to trace a path in the field that we continue to follow. His name will remain in the textbooks and articles he authored. Here, as colleagues and friends who had the honor to work with him, we provide our personal views of Alessandro's impact and legacy, which go far beyond his publications.
PMID: 39403746
ISSN: 1557-8992
CID: 5711042
Implementation and validation of single-cell genomics experiments in neuroscience
Single-cell or single-nucleus transcriptomics is a powerful tool for identifying cell types and cell states. However, hypotheses derived from these assays, including gene expression information, require validation, and their functional relevance needs to be established. The choice of validation depends on numerous factors. Here, we present types of orthogonal and functional validation experiment to strengthen preliminary findings obtained using single-cell and single-nucleus transcriptomics as well as the challenges and limitations of these approaches.
PMID: 39627589
ISSN: 1546-1726
CID: 5763782
Leptin-activated hypothalamic BNC2 neurons acutely suppress food intake
Leptin is an adipose tissue hormone that maintains homeostatic control of adipose tissue mass by regulating the activity of specific neural populations controlling appetite and metabolism1. Leptin regulates food intake by inhibiting orexigenic agouti-related protein (AGRP) neurons and activating anorexigenic pro-opiomelanocortin (POMC) neurons2. However, whereas AGRP neurons regulate food intake on a rapid time scale, acute activation of POMC neurons has only a minimal effect3-5. This has raised the possibility that there is a heretofore unidentified leptin-regulated neural population that rapidly suppresses appetite. Here we report the discovery of a new population of leptin-target neurons expressing basonuclin 2 (Bnc2) in the arcuate nucleus that acutely suppress appetite by directly inhibiting AGRP neurons. Opposite to the effect of AGRP activation, BNC2 neuronal activation elicited a place preference indicative of positive valence in hungry but not fed mice. The activity of BNC2 neurons is modulated by leptin, sensory food cues and nutritional status. Finally, deleting leptin receptors in BNC2 neurons caused marked hyperphagia and obesity, similar to that observed in a leptin receptor knockout in AGRP neurons. These data indicate that BNC2-expressing neurons are a key component of the neural circuit that maintains energy balance, thus filling an important gap in our understanding of the regulation of food intake and leptin action.
PMID: 39478220
ISSN: 1476-4687
CID: 5747152
DeepEMC-T2 mapping: Deep learning-enabled T2 mapping based on echo modulation curve modeling
PURPOSE/OBJECTIVE:maps from fewer echoes. METHODS:mapping was evaluated in seven experiments. RESULTS:estimation. CONCLUSIONS:estimation from fewer echoes allows for increased volumetric coverage and/or higher slice resolution without prolonging total scan times.
PMCID:11436299
PMID: 39129209
ISSN: 1522-2594
CID: 5706952
Applying single-cell and single-nucleus genomics to studies of cellular heterogeneity and cell fate transitions in the nervous system
Single-cell and single-nucleus genomic approaches can provide unbiased and multimodal insights. Here, we discuss what constitutes a molecular cell atlas and how to leverage single-cell omics data to generate hypotheses and gain insights into cell transitions in development and disease of the nervous system. We share points of reflection on what to consider during study design and implementation as well as limitations and pitfalls.
PMID: 39627588
ISSN: 1546-1726
CID: 5763772
Opportunities and challenges of single-cell and spatially resolved genomics methods for neuroscience discovery
Over the past decade, single-cell genomics technologies have allowed scalable profiling of cell-type-specific features, which has substantially increased our ability to study cellular diversity and transcriptional programs in heterogeneous tissues. Yet our understanding of mechanisms of gene regulation or the rules that govern interactions between cell types is still limited. The advent of new computational pipelines and technologies, such as single-cell epigenomics and spatially resolved transcriptomics, has created opportunities to explore two new axes of biological variation: cell-intrinsic regulation of cell states and expression programs and interactions between cells. Here, we summarize the most promising and robust technologies in these areas, discuss their strengths and limitations and discuss key computational approaches for analysis of these complex datasets. We highlight how data sharing and integration, documentation, visualization and benchmarking of results contribute to transparency, reproducibility, collaboration and democratization in neuroscience, and discuss needs and opportunities for future technology development and analysis.
PMID: 39627587
ISSN: 1546-1726
CID: 5763762
