Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Neuroscience Institute
Total Results:
13426
Virtual Ontogeny of Cortical Growth Preceding Mental Illness
BACKGROUND:Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. METHODS:Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. RESULTS:Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. CONCLUSIONS:Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
PMID: 35489875
ISSN: 1873-2402
CID: 5217792
Preemptive Removal of Small, Asymptomatic Kidney Stones [Editorial]
PMID: 35947713
ISSN: 1533-4406
CID: 5286962
A neural circuit for wind-guided olfactory navigation
To navigate towards a food source, animals frequently combine odor cues about source identity with wind direction cues about source location. Where and how these two cues are integrated to support navigation is unclear. Here we describe a pathway to the Drosophila fan-shaped body that encodes attractive odor and promotes upwind navigation. We show that neurons throughout this pathway encode odor, but not wind direction. Using connectomics, we identify fan-shaped body local neurons called h∆C that receive input from this odor pathway and a previously described wind pathway. We show that h∆C neurons exhibit odor-gated, wind direction-tuned activity, that sparse activation of h∆C neurons promotes navigation in a reproducible direction, and that h∆C activity is required for persistent upwind orientation during odor. Based on connectome data, we develop a computational model showing how h∆C activity can promote navigation towards a goal such as an upwind odor source. Our results suggest that odor and wind cues are processed by separate pathways and integrated within the fan-shaped body to support goal-directed navigation.
PMCID:9360402
PMID: 35941114
ISSN: 2041-1723
CID: 5286712
IN-HOME-PD: The effects of longitudinal telehealth-enhanced interdisciplinary home visits on care and quality of life for homebound individuals with Parkinson's disease
INTRODUCTION/BACKGROUND:Homebound individuals with advanced Parkinson's disease (PD) are underrepresented in research and care. We tested the impact of interdisciplinary, telehealth-enhanced home visits (IN-HOME-PD) on patient quality of life (QoL) compared with usual care. METHODS:Nonrandomized controlled trial of quarterly, structured, telehealth-enhanced interdisciplinary home visits focused on symptom management, home safety, medication reconciliation, and psychosocial needs (ClinicalTrials.gov NCT03189459). We enrolled homebound participants with advanced PD (Hoehn & Yahr (HY) stage ≥3). Usual care participants had ≥2 visits in the Parkinson's Outcomes Project (POP) registry. We compared within- and between-group one-year change in QoL using the Parkinson's Disease Questionnaire. RESULTS:Sixty-five individuals enrolled in IN-HOME-PD (32.3% women; mean age 78.9 (SD 7.6) years; 74.6% white; 78.5% HY ≥ 4) compared with 319 POP controls, with differences in age, race, and PD severity (37.9% women; mean age 70.1 (7.8) years; 96.2% white; 15.1% HY ≥ 4). Longitudinally, the intervention group's QoL remained unchanged (within-group p = 0.74, Cohen's d = 0.05) while QoL decreased over time in POP controls (p < 0.001, Cohen's d = 0.27). The difference favored the intervention (between-group p = 0.04). POP participants declined in 7/8 dimensions while IN-HOME-PD participants' bodily discomfort improved and hospice use and death at home-markers of goal-concordant care-far exceeded national data. CONCLUSIONS:Telehealth-enhanced home visits can stabilize and may improve the predicted QoL decline in advanced PD via continuity of care and facilitating goal-concordant care, particularly among diverse populations. Extrapolating features of this model may improve continuity of care and outcomes in advanced PD.
PMID: 35963046
ISSN: 1873-5126
CID: 5287442
Publisher Correction: Recurrent somatic mutations as predictors of immunotherapy response
PMID: 35931739
ISSN: 2041-1723
CID: 5288392
Mapping the vocal circuitry of Alston's singing mouse with pseudorabies virus
Vocalizations are often elaborate, rhythmically structured behaviors. Vocal motor patterns require close coordination of neural circuits governing the muscles of the larynx, jaw, and respiratory system. In the elaborate vocalization of Alston's singing mouse (Scotinomys teguina) each note of its rapid, frequency-modulated trill is accompanied by equally rapid modulation of breath and gape. To elucidate the neural circuitry underlying this behavior, we introduced the polysynaptic retrograde neuronal tracer pseudorabies virus (PRV) into the cricothyroid and digastricus muscles, which control frequency modulation and jaw opening, respectively. Each virus singly labels ipsilateral motoneurons (nucleus ambiguus for cricothyroid, and motor trigeminal nucleus for digastricus). We find that the two isogenic viruses heavily and bilaterally colabel neurons in the gigantocellular reticular formation, a putative central pattern generator. The viruses also show strong colabeling in compartments of the midbrain including the ventrolateral periaqueductal gray and the parabrachial nucleus, two structures strongly implicated in vocalizations. In the forebrain, regions important to social cognition and energy balance both exhibit extensive colabeling. This includes the paraventricular and arcuate nuclei of the hypothalamus, the lateral hypothalamus, preoptic area, extended amygdala, central amygdala, and the bed nucleus of the stria terminalis. Finally, we find doubly labeled neurons in M1 motor cortex previously described as laryngeal, as well as in the prelimbic cortex, which indicate these cortical regions play a role in vocal production. The progress of both viruses is broadly consistent with vertebrate-general patterns of vocal circuitry, as well as with circuit models derived from primate literature.
PMID: 35385140
ISSN: 1096-9861
CID: 5204932
Comparison of empiric preventative pharmacologic therapies on stone recurrence among patients with kidney stone disease
OBJECTIVE:To compare the frequency of stone-related events among patients receiving thiazides, alkali citrate, and allopurinol without prior 24-hour urine testing.  It is unknown whether one preventative pharmacological therapy (PPT) medication class is more beneficial for reducing kidney stone recurrence when prescribed empirically. MATERIALS AND METHODS/METHODS:Using medical claims data from working-age adults with kidney stone disease diagnoses (2008-2018), we identified those prescribed thiazides, alkali citrate, or allopurinol. We excluded those who received 24-hour urine testing prior to initiating PPT and those with less than three years of follow-up. We fit multivariable regression models to estimate the association between the occurrence of a stone-related event (emergency department visit, hospitalization, or surgery for stones) and PPT medication class. RESULTS:Our cohort consisted of 1,834 (60%), 654 (21%), and 558 (18%) patients empirically prescribed thiazides, alkali citrate, or allopurinol, respectively. After controlling for patient factors including medication adherence and concomitant conditions that increase recurrence risk, the adjusted rate of any stone event was lowest for the thiazide group (14.8%) compared to alkali citrate (20.4%) or allopurinol (20.4%) (each p<0.001). Thiazides, compared to allopurinol, were associated with 32% lower odds of a subsequent stone event by three years (OR 0.68, 95% CI 0.53-0.88). No such association was observed when comparing alkali citrate to allopurinol (OR 1.00, 95% CI 0.75-1.34). CONCLUSIONS:Empiric PPT with thiazides is associated with significantly lower odds of subsequent stone-related events. When 24-hour urine testing is unavailable, thiazides may be preferred over alkali citrate or allopurinol for empiric PPT.
PMID: 35545149
ISSN: 1527-9995
CID: 5214482
Cystinuria: an update on pathophysiology, genetics, and clinical management
Cystinuria is the most common genetic cause of nephrolithiasis in children. It is considered a heritable aminoaciduria as the genetic defect affects the reabsorption of cystine and three other amino acids (ornithine, lysine, and arginine) in the renal proximal tubule. Patients affected by this condition have elevated excretion of cystine in the urine, and because of this amino acid's low solubility at normal urine pH, patients tend to form cystine calculi. To date, two genes have been identified as disease-causative: SLC3A1 and SLC7A9, encoding for the two subunits of the heterodimeric transporter. The clinical features of this condition are solely related to nephrolithiasis. The diagnosis is usually made during infancy or adolescence, but cases of late diagnosis are common. The goal of therapy is to reduce excretion and increase the solubility of cystine, through both modifications of dietary habits and pharmacological treatment. However, therapeutic interventions are not always sufficient, and patients often have to undergo several surgical procedures during their lives to treat recurrent nephrolithiasis. The goal of this literature review is to synthesize the available evidence on diagnosis and management of patients affected by cystinuria in order to provide physicians with a practical tool that can be used in daily clinical practice. This review also aims to shed some light on new therapy directions with the aim of ameliorating kidney outcomes while improving adherence to treatment and quality of life of cystinuric patients.
PMID: 34812923
ISSN: 1432-198x
CID: 5063522
PGT-A: The biology and hidden failures of randomized control trials
OBJECTIVE:Preimplantation Genetic Testing - Aneuploidy (PGT-A) for embryo selection has undergone significant advancements in the last 2 decades and yet many studies still fail to demonstrate any clinical benefits over traditional embryo morphology selection (Mo-S). To understand this conundrum, we performed a multi-center clinical study of PGT-A patients, where Mo-S and euploid selection (Eu-S) outcomes were directly compared. METHOD:All suitable blastocysts were biopsied and analyzed for chromosome copy number. Outcomes (positive beta hCG, implantation, ongoing pregnancy, and live birth rates) for Eu-S were compared to Mo-S using single embryo transfers. RESULTS:Compared to Eu-S embryos, Mo-S embryos resulted in significant reduction of outcomes for positive beta hCG (p = 0.0005), implantation (p = 0.0008), ongoing pregnancy (p = 0.0046), livebirth (p = 0.0112), babies per transfer (p = 0.0112), and babies per embryo transferred (p = 0.0112). Morphology selection resulted in patients of all age groups having non-euploid embryos chosen for transfer. Post-hoc evaluation of individual clinic performances showed variable transfer outcomes that could potentially confound the true benefits of PGT-A. CONCLUSION:Embryo chromosome status is central to improved embryo transfer outcomes and sole reliance on current morphology-based selection practices, without Eu-S, will always compromise outcomes. Often overlooked but a major effector of successful PGT-A outcomes are individual clinic performances.
PMID: 35765263
ISSN: 1097-0223
CID: 5321682
Defining existing practices to support the sleep of hospitalized patients: A mixed-methods study of top-ranked hospitals
The objective of this study was to understand the existing practices and attitudes regarding inpatient sleep at the 2020 US News and World Report (USNWR) Honor Roll pediatric (n = 10) and adult (n = 20) hospitals. Section chiefs of Hospital Medicine from these institutions were surveyed and interviewed between June and August 2021. Among 23 of 30 surveyed physician leaders (response rate = 77%), 96% (n = 22) rated patient sleep as important, but only 43% (n = 10) were satisfied with their institutions' efforts. A total of 96% (n = 22) of institutions lack sleep equity practices. Fewer than half (48%) of top hospitals have sleep-friendly practices, with the most common practices including reducing overnight vital sign monitoring (43%), decreasing ambient light in the wards (43%), adjusting lab and medication schedules (35%), and implementing quiet hours (30%). Major themes from qualitative interviews included: importance of universal sleep-friendly cultures, environmental changes, and external incentives to improve patient sleep.
PMID: 35854665
ISSN: 1553-5606
CID: 5279012
