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Drive-through coronavirus disease 2019 screening can evaluate large numbers of patients while reducing healthcare exposures and personal protective equipment use. We describe the characteristics of screened individuals as well as drive-through process and outcome measures. Optimal drive-through screening involves rapid turnaround of test results and linkage to follow-up care., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2020.)

Background: There are no data on the effect of exogenous corticosterone on depressive-like behavior in juvenile rats. Furthermore, it has not been tested whether the effects of corticosterone in female rats is different before or after puberty., Objective: We tested the effect of corticosterone treatment on female pre- and peri-pubescent juvenile rats on depressive-like behavior., Methods: Female juvenile rats were divided into pre-pubescent (post-natal day 7-27) or peri-pubescent (post-natal day 28-48) groups and administered daily corticosterone (40 mg kg -1  day -1 ) for 21 days. Depressive-like behavior was assessed using a modified forced swim test and the sucrose preference test. After behavioral assessment, brains were analyzed to determine if there were changes in cell proliferation and newborn neuron survival in the dentate gyrus of the dorsal hippocampus., Results: Chronic corticosterone treatment did not affect behavior or neurogenesis in female pre-pubescent juvenile rats. However, female peri-pubescent rats injected with corticosterone showed increased depressive-like behavior as well as a decrease in cell proliferation in the subgranular zone. Furthermore, there was an inverse correlation between time spent immobile in the forced swim test and cell proliferation in the granule cell layer in peri-pubescent rats., Conclusions: Corticosterone induces depressive-like behavior in peri-pubescent, but not in pre-pubescent female rats. Finally, our results suggest that depressive-like behavior may be associated with a decrease in hippocampal cell proliferation in female peri-pubescent rats., (© The Author(s) 2020.)

During development, neurons undergo apoptosis if they do not receive adequate trophic support from tissues they innervate or when detrimental factors activate the p75 neurotrophin receptor (p75NTR) at their axon ends. Trophic factor deprivation (TFD) or activation of p75NTR in distal axons results in a retrograde degenerative signal. However, the nature of this signal and the regulation of its transport are poorly understood. Here, we identify p75NTR intracellular domain (ICD) and histone deacetylase 1 (HDAC1) as part of a retrograde pro-apoptotic signal generated in response to TFD or ligand binding to p75NTR in sympathetic neurons. We report an unconventional function of HDAC1 in retrograde transport of a degenerative signal and its constitutive presence in sympathetic axons. HDAC1 deacetylates dynactin subunit p150 Glued , which enhances its interaction with dynein. These findings define p75NTR ICD as a retrograde degenerative signal and reveal p150 Glued deacetylation as a unique mechanism regulating axonal transport., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The p75 neurotrophin receptor (p75NTR) plays an integral role in patterning the sympathetic nervous system during development. Initially, p75NTR is expressed at low levels as sympathetic axons project toward their targets, which enables neurotrophin-3 (NT3) to activate TrkA receptors and promote growth. Upon reaching nerve growth factor (NGF) producing tissues, p75NTR is upregulated, resulting in formation of TrkA-p75 complexes, which are high-affinity binding sites selective for NGF, thereby blunting NT3 signaling. The level of p75NTR expressed on the neuron surface is instrumental in regulating trophic factor response; however, the mechanisms by which p75NTR expression is regulated are poorly understood. Here, we demonstrate a rapid, translation independent increase in surface expression of p75NTR in response to NGF in rat sympathetic neurons. p75NTR was mobilized to the neuron surface from GGA3-postitive vesicles through activation of the GTPase Arf6, which was stimulated by NGF, but not NT3 binding to TrkA. Arf6 activation required PI3 kinase activity and was prevented by an inhibitor of the cytohesin family of Arf6 guanine nucleotide exchange factors. Overexpression of a constitutively active Arf6 mutant (Q67L) was sufficient to significantly increase surface expression of p75NTR even in the absence of NGF. Functionally, expression of active Arf6 markedly attenuated the ability of NT3 to promote neuronal survival and neurite outgrowth, whereas the NGF response was unaltered. These data suggest that NGF activation of Arf6 through TrkA is critical for the increase in p75NTR surface expression that enables the switch in neurotrophin responsiveness during development in the sympathetic nervous system. SIGNIFICANCE STATEMENT p75NTR is instrumental in the regulation of neuronal survival and apoptosis during development and is also implicated as a contributor to aberrant neurodegeneration in numerous conditions. Therefore, a better understanding of the mechanisms that mediate p75NTR surface availability may provide insight into how and why neurodegenerative processes manifest and reveal new therapeutic targets. Results from this study indicate a novel mechanism by which p75NTR can be rapidly shuttled to the cell surface from existing intracellular pools and explores a unique pathway by which NGF regulates the sympathetic innervation of target tissues, which has profound consequences for the function of these organs., (Copyright © 2018 the authors 0270-6474/18/385606-14$15.00/0.)

Trichotillomania (TTM) was long classified as an impulse-control disorder; however, the many characteristics it shares with obsessive-compulsive disorder (OCD) led to its recategorization in the DSM-V. The present study aimed to assess and inform the taxonomic placement of TTM through an examination of its neural correlates. While research has consistently associated OCD with enhanced response monitoring, the present study investigated whether a similar neural process is associated with TTM. Undergraduates reporting TTM symptoms and controls performed a modified version of the flanker task, and their event-related potentials were examined for between-group differences in error-related negativity (ERN). Results confirm that individuals who have symptoms of hair pulling have significantly smaller ERNs than the control group. Smaller ERNs reflect decreased levels of response monitoring and support the idea that TTM is distinct from OCD., (Copyright © 2014 Society for Psychophysiological Research.)

Background: Approximately 18% of pregnant women continue to smoke tobacco cigarettes throughout pregnancy. Offspring exposed to tobacco smoke in utero exhibit a higher incidence of drug use in later stages of development relative to non-exposed children. Animal models indicate that prenatal nicotine (PN) exposure alone alters the development of the mesocorticolimbic dopamine (DA) system, which, in part, organizes motivated behavior and reward. The orexin/hypocretin neuropeptide system, which originates in the lateral hypothalamus (LH), projects to key areas of the mesocorticolimbic DA pathway. Previous research suggests that orexin exerts a major influence on motivation and reward., Methods: The present experiments determined if intravenous (IV) PN exposure alters (1) the expression of orexin neurons and melanin-concentrating hormone (MCH; positive control) in the LH; and (2) orexin projections from the LH onto DA neurons in the ventral tegmental area (VTA). Dams were injected with IV nicotine (0.05 mg/kg/injection) or saline 3×/day during gestational days 8-21. Tissues from adult male offspring (∼130 days) were examined using immunohistochemistry., Results: Relative to controls, offspring of IV PN exposure showed (1) increased numbers of orexin neurons in the LH, and no changes in the expression of MCH; and (2) increased orexin appositions on DA cells in the VTA., Conclusion: The findings indicate that the influence of PN exposure is enduring, and suggests that the PN-induced modification of orexin expression on mesolimbic circuitry may contribute to the reported changes in motivated behaviors related to food and drug reward observed in offspring prenatally exposed to nicotine., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The medial septum (MS) of the basal forebrain contains cholinergic neurons that project to the hippocampus, support cognitive function, and are implicated in age-related cognitive decline. Hypothalamic orexin/hypocretin neurons innervate and modulate basal forebrain cholinergic neurons and provide direct inputs to the hippocampus. However, the precise role of orexin in modulating hippocampal cholinergic transmission--and how these interactions are altered in aging--is unknown. Here, orexin A was administered to CA1 and the MS of young (3-4 months) and aged (27-29 months) Fisher 344/Brown Norway rats, and hippocampal acetylcholine efflux was analyzed by in vivo microdialysis. At both infusion sites, orexin A dose-dependently increased hippocampal acetylcholine in young, but not aged rats. Moreover, immunohistochemical characterization of the MS revealed no change in cholinergic cell bodies in aged animals, but a significant decrease in orexin fiber innervation to cholinergic cells. These findings indicate that: (1) Orexin A modulates hippocampal cholinergic neurotransmission directly and transsynaptically in young animals, (2) Aged animals are unresponsive to orexin A, and (3) Aged animals undergo an intrinsic reduction in orexin innervation to cholinergic cells within the MS. Alterations in orexin regulation of septohippocampal cholinergic activity may contribute to age-related dysfunctions in arousal, learning, and memory., (Copyright © 2011 Wiley Periodicals, Inc.)

The color word Stroop effect in bilinguals is commonly half the magnitude when the written and naming languages are different (between) than when they are the same (within). This between-within language Stroop difference (BWLS) is likened to a response set effect, with greater response conflict for response relevant than irrelevant words. The nature of the BWLS was examined using a bilingual Stroop task. In a given block (Experiment 1), color congruent and incongruent words appeared in the naming language or not (single), or randomly in both languages (mixed). The BWLS effect was present for both balanced and unbalanced bilinguals, but only partially supported a response set explanation. As expected, color incongruent trials during single language blocks, lead to slower response times within than between languages. However, color congruent trials during mixed language blocks led to slower times between than within languages, indicating that response-irrelevant stimuli interfered with processing. In Experiment 2, to investigate the neural timing of the BWLS effect, event related potentials were recorded while balanced bilinguals named silently within and between languages. Replicating monolingual findings, an N450 effect was observed with larger negative amplitude for color incongruent than congruent trials (350-550 ms post-stimulus onset). This effect was equivalent within and between languages, indicating that color words from both languages created response conflict, contrary to a strict response set effect. A sustained negativity (SN) followed with larger amplitude for color incongruent than congruent trials, resolving earlier for between than within language Stroop. This effect shared timing (550-700 ms), but not morphology or scalp distribution with the commonly reported sustained potential. Finally, larger negative amplitude (200-350 ms) was observed between than within languages independent of color congruence. This negativity, likened to a no-go N2, may reflect processes of inhibitory control that facilitate the resolution of conflict at the SN, while the N450 reflects parallel processing of distracter words, independent of response set (or language). In sum, the BWLS reflects brain activity over time with contributions from language and color conflict at different points.

Several lines of evidence point to a role for the hippocampal formation and contiguous temporal lobe structures in a variety of learning and memory paradigms. Presumably, these cognitive phenomena are mediated (and accompanied) by dynamic changes in neurochemical transmission that may differ between learning and recall phases. However, the neurotransmitter correlates of most memory-related tasks have not been thoroughly investigated. Here we used a one-trial object recognition paradigm paired with in vivo microdialysis to assess hippocampal acetylcholine (ACh), glutamate and GABA efflux when rats were exposed to familiar objects, and when given the option to explore familiar and novel objects. Rats preferentially explored the novel object over the familiar one when presented with the option. Regardless of object familiarity, object exploration was accompanied by an increase in hippocampal ACh efflux, while GABA efflux was unaffected. However, glutamate efflux was not increased above baseline levels by presentation of familiar objects, but was significantly enhanced in the presence of the novel object. These data suggest that the hippocampus, and in particular, hippocampal glutamate, may be involved in memory processes during novelty recognition paradigms., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Aging is associated with impairments in learning and memory and a greater incidence of limbic seizures. These changes in the aged brain have been associated with increased excitability of hippocampal pyramidal cells caused by a reduced number of gamma-aminobutyric acid-ergic (GABAergic) interneurons. To better understand these issues, we performed cell counts of GABAergic interneurons and examined GABA efflux and GABAergic inhibition in area CA1 of the hippocampus of young (3-5 months) and aged (26-30 months) rats. Aging significantly reduced high K(+)/Ca(2+)-evoked GABA, but not glutamate efflux in area CA1. Immunostaining revealed a significant loss of GABAergic interneurons, but not inhibitory boutons in stratum oriens and stratum lacunosum moleculare. Somatostatin-immunoreactive oriens-lacunosum moleculare (O-LM) cells, but not parvalbumin-containing interneurons were selectively lost. Oriens-lacunosum moleculare cells project to distal dendrites of CA1 pyramidal cells, providing dendritic inhibition. Accordingly, inhibition of dendritic input to CA1 from entorhinal cortex was selectively reduced. These findings suggest that the age-dependent loss of interneurons impairs dendritic inhibition and dysregulates entorhinal cortical input to CA1, potentially contributing to cognitive impairment and seizures., (Copyright © 2012 Elsevier Inc. All rights reserved.)

GABAergic neurons of the medial septum of the basal forebrain make up a substantial portion of the septo-hippocampal pathway fibers, and are known to modulate hippocampal amino acid neurotransmission and support cognitive function. Importantly, these neurons are also implicated in age-related cognitive decline. Hypothalamic orexin/hypocretin neurons innervate and modulate the activity of these basal forebrain neurons and also provide direct inputs to the hippocampus. However, the precise role of orexin inputs in modulating hippocampal amino acid neurotransmission--as well as how these interactions are altered in aging--has not been defined. Here, orexin A (OxA) was administered to CA1 and the medial septum of young (3-4 months) and aged (27-29 months) Fisher 344 Brown Norway rats, and hippocampal GABA and glutamate efflux was analyzed by in vivo microdialysis. Following CA1 infusion of OxA, extracellular GABA and glutamate efflux was increased, but the magnitude of orexin-mediated efflux was not altered as a function of age. However, medial septum infusion of OxA did not impact hippocampal efflux in young rats, while aged rats exhibited a significant enhancement in GABA and glutamate efflux compared to young counterparts. Furthermore, immunohistochemical characterization of the medial septum revealed a significant decrease in parvalbumin (PV)-positive cell bodies in aged animals, and a significant reduction in orexin fiber innervation to the remaining GABAergic cells within the septum, while orexin innervation to the hippocampus was unaltered by the aging process. These findings indicate that: (1) OxA directly modulates hippocampal amino acid neurotransmission in young animals, (2) Aged animals show enhanced responsivity to exogenous OxA activation of the septo-hippocampal pathway, and (3) Aged animals undergo an intrinsic reduction in medial septum PV-immunoreactivity and a decrease in orexin innervation to remaining septal PV neurons. Alterations in orexin regulation of septo-hippocampal activity may contribute to age-related dysfunctions in arousal, learning, and memory., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

Native tone language experience has been linked with alterations in the production and perception of pitch in language, as well as with the brain response to linguistic and non-linguistic tones. Here we use two experiments to address whether these changes apply to the discrimination of simple pitch changes and pitch intervals. Event related potentials (ERPs) were recorded from native Mandarin speakers and a control group during a same/different task with pairs of pure tones differing only in pitch height, and with pure tone pairs differing only in interval distance. Behaviorally, Mandarin speakers were more accurate than controls at detecting both pitch and interval changes, showing a sensitivity to small pitch changes and interval distances that was absent in the control group. Converging evidence from ERPs obtained during the same tasks revealed an earlier response to change relative to no-change trials in Mandarin speakers, as well as earlier differentiation of trials by change direction relative to controls. These findings illustrate the cross-domain influence of language experience on the perception of pitch, suggesting that the native use of tonal pitch contours in language leads to a general enhancement in the acuity of pitch representations.

Aging is associated with many physiological alterations-such as changes in sleep patterns, metabolism and food intake-suggestive of hypothalamic dysfunction, but the effects of senescence on specific hypothalamic nuclei and neuronal groups that mediate these alterations is unclear. The lateral hypothalamus and contiguous perifornical area (LH/PFA) contains several populations of neurons, including those that express the neuropeptides orexin (hypocretin) or melanin-concentrating hormone (MCH). Collectively, orexin and MCH neurons influence many integrative homeostatic processes related to wakefulness and energy balance. Here, we determined the effect of aging on numbers of orexin and MCH neurons in young adult (3-4 months) and old (26-28 months) Fisher 344/Brown Norway F1 hybrid rats. Aged rats exhibited a loss of greater than 40% of orexin-immunoreactive neurons in both the medial and lateral (relative to the fornix) sectors of the LH/PFA. MCH-immunoreactive neurons were also lost in aged rats, primarily in the medial LH/PFA. Neuronal loss in this area was not global as no change in cells immunoreactive for the pan-neuronal marker, NeuN, was observed in aged rats. Combined with other reports of altered receptor expression or behavioral responses to exogenously-administered neuropeptide, these data suggest that compromised orexin (and, perhaps, MCH) function is an important mediator of age-related homeostatic disturbances of hypothalamic origin. The orexin system may represent a crucial substrate linking homeostatic and cognitive dysfunction in aging, as well as a novel therapeutic target for pharmacological or genetic restoration approaches to preventing or ameliorating these disturbances., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

Polymorphisms in the regulatory regions of cytokine genes are associated with high and low cytokine production and may modulate the magnitude of alloimmune responses following transplantation. Ethnicity influences allograft half-life and the incidence of acute and chronic rejection. We have questioned whether ethnic-based differences in renal allograft survival could be due in part to inheritance of cytokine polymorphisms. To address that question, we studied the inheritance patterns for polymorphisms in several cytokine genes (IL-2, IL-6, IL-10, TNF-alpha, TGF-beta, and IFN-gamma) within an ethnically diverse study population comprised of 216 Whites, 58 Blacks, 25 Hispanics, and 31 Asians. Polymorphisms were determined by allele-specific polymerase chain reaction and restriction fragment length analysis. We found striking differences in the distribution of cytokine polymorphisms among ethnic populations. Specifically, significant differences existed between Blacks and both Whites and Asians in the distribution of the polymorphic alleles for IL-2. Blacks, Hispanics and Asians demonstrated marked differences in the inheritance of IL-6 alleles and IL-10 genotypes that result in high expression when compared with Whites. Those of Asian descent exhibited an increase in IFN-gamma genotypes that result in low expression as compared to Whites. In contrast, we did not find significant ethnic-based differences in the inheritance of polymorphic alleles for TNF-alpha. Our results show that the inheritance of certain cytokine gene polymorphisms is strongly associated with ethnicity. These differences may contribute to the apparent influence of ethnicity on allograft outcome.

Background: Genetic variations in cytokine genes are thought to regulate cytokine protein production. However, studies using T cell mitogens have not always demonstrated a significant relationship between cytokine polymorphisms and in vitro protein production. Furthermore, the functional consequence of a polymorphism at position -330 in the IL-2 gene has not been described. We associated in vitro protein production with cytokine gene polymorphic genotypes after costimulation of cultured peripheral blood lymphocytes., Methods: PBL were isolated from forty healthy volunteers. Cytokine protein production was assessed by enzyme-linked immunosorbent assay. Polymorphisms in interleukin- (IL) 2, IL-6, IL-10, tumor necrosis factor (TNF-alpha), tumor growth factor (TGF-beta), and interferon (IFN-gamma) were determined by polymerase chain reaction (PCR)., Results: Statistical difference between protein production and cytokine polymorphic variants in the IL-10, IFN-gamma, and TNF-alpha genes was not evident after 48-hour stimulation with concanavalin-A. In contrast, after anti-CD3/CD28 stimulation significant differences (P<0.05) were found among high and low producers for IL-2, IL-6, and among high, intermediate, and low producers for IFN-gamma, and IL-10. Augmented levels of IL-2 in individuals that were homozygous for the polymorphic IL-2 allele were due to an early and sustained enhancement of IL-2 production. No association was found among TNF-alpha and TGF-beta genotypes and protein production., Conclusion: Polymorphisms in IL-2, IL-6, IL-10, and IFN-gamma genes are associated with their protein production after anti-CD3/CD28 stimulation. The profound effect of the IL-2 gene polymorphism in homozygous individuals may serve as a marker for those that could mount the most vigorous allo- or autoimmune responses, or perhaps become tolerant more easily.