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  1. Article ; Online: How Should Cognitive Impairment Be Recognized?

    Fargo, Keith N / Cordell, Cyndy B / Carrillo, Maria C

    Journal of the American Medical Directors Association

    2015  Volume 16, Issue 10, Page(s) 813–814

    MeSH term(s) Aged ; Cognitive Dysfunction/diagnosis ; Consensus Development Conferences as Topic ; Dementia/diagnosis ; Geriatric Assessment ; Humans
    Language English
    Publishing date 2015-10-01
    Publishing country United States
    Document type Editorial
    ZDB-ID 2171030-2
    ISSN 1538-9375 ; 1525-8610
    ISSN (online) 1538-9375
    ISSN 1525-8610
    DOI 10.1016/j.jamda.2015.08.006
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  2. Article ; Online: Bupivacaine increases the rate of motoneuron death following peripheral nerve injury.

    Byram, Susanna C / Byram, Scott W / Miller, Nicholas M / Fargo, Keith N

    Restorative neurology and neuroscience

    2017  Volume 35, Issue 1, Page(s) 129–135

    Abstract: Background: Appropriate management of pain after an injury or surgical procedure has been shown to improve patient outcomes. While infrequent, nerve damage resulting from regional anesthesia can be devastating, however the mechanism remains unknown. ... ...

    Abstract Background: Appropriate management of pain after an injury or surgical procedure has been shown to improve patient outcomes. While infrequent, nerve damage resulting from regional anesthesia can be devastating, however the mechanism remains unknown. Local anesthetics are neurotoxic yet are frequently applied to sites where peripheral nerves are regenerating. Therefore, understanding their effects on injured and growing neurons may have important implications for clinical practice.
    Objective: The purpose of this study was to determine if local anesthetics exacerbate the rate of motoneuron death following axotomy.
    Methods: Mice were subjected to a unilateral transection of the facial motor nerve, and either normal saline, 2% lidocaine, or 0.75% bupivacaine was placed at the injury site. Four weeks post-axotomy, percent survival was determined by comparing the number of motoneuron cell bodies on the injured side and the uninjured control side.
    Results: The average facial motoneuron survival in the saline, lidocaine, and bupivacaine groups 4 weeks after axotomy was 80%, 78% and 35%, respectively.
    Conclusion: Our data suggest that bupivacaine exacerbates levels of cell death in injured motoneurons. It has been proposed that once a nerve is damaged, it becomes more susceptible to injury elsewhere along the nerve. Thus, an improved understanding of the effects of local anesthetics on neuron survival and axon regeneration may lead to strategies to identify patients at higher risk for permanent neural deficits after peripheral nerve blocks and/or decrease the risk of neural deficit following peripheral nerve blocks.
    Language English
    Publishing date 2017
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1017098-4
    ISSN 1878-3627 ; 0922-6028
    ISSN (online) 1878-3627
    ISSN 0922-6028
    DOI 10.3233/RNN-160692
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  3. Article ; Online: The crisis in recruitment for clinical trials in Alzheimer's and dementia: An action plan for solutions.

    Fargo, Keith N / Carrillo, Maria C / Weiner, Michael W / Potter, William Z / Khachaturian, Zaven

    Alzheimer's & dementia : the journal of the Alzheimer's Association

    2016  Volume 12, Issue 11, Page(s) 1113–1115

    Language English
    Publishing date 2016
    Publishing country United States
    Document type Editorial
    ZDB-ID 2211627-8
    ISSN 1552-5279 ; 1552-5260
    ISSN (online) 1552-5279
    ISSN 1552-5260
    DOI 10.1016/j.jalz.2016.10.001
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  4. Article ; Online: Committee on High-quality Alzheimer's Disease Studies (CHADS) consensus report.

    Jicha, Greg A / Abner, Erin L / Arnold, Steven E / Carrillo, Maria C / Dodge, Hiroko H / Edland, Steven D / Fargo, Keith N / Feldman, Howard H / Goldstein, Larry B / Hendrix, James / Peters, Ruth / Robillard, Julie M / Schneider, Lon S / Titiner, Jodi R / Weber, Christopher J

    Alzheimer's & dementia : the journal of the Alzheimer's Association

    2021  Volume 18, Issue 6, Page(s) 1109–1118

    Abstract: Background: Consensus guidance for the development and identification of high-quality Alzheimer's disease clinical trials is needed for protocol development and conduct of clinical trials.: Methods: An ad hoc consensus committee was convened in ... ...

    Abstract Background: Consensus guidance for the development and identification of high-quality Alzheimer's disease clinical trials is needed for protocol development and conduct of clinical trials.
    Methods: An ad hoc consensus committee was convened in conjunction with the Alzheimer's Association to develop consensus recommendations.
    Results: Consensus was readily reached for the need to provide scientific justification, registration of trials, institutional review board oversight, conflict of interest disclosure, funding source disclosure, defined trial population, recruitment resources, definition of the intervention, specification of trial duration, appropriate payment for participant engagement, risk-benefit disclosure as part of the consent process, and the requirement to disseminate and/or publish trial results even if the study is negative.
    Conclusions: This consensus guidance should prove useful for the protocol development and conduct of clinical trials, and may further provide a platform for the development of education materials that may help guide appropriate clinical trial participation decisions for potential trial participants and the general public.
    MeSH term(s) Alzheimer Disease ; Consensus ; Disclosure ; Ethics Committees, Research ; Humans ; Research Design
    Language English
    Publishing date 2021-09-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2211627-8
    ISSN 1552-5279 ; 1552-5260
    ISSN (online) 1552-5279
    ISSN 1552-5260
    DOI 10.1002/alz.12461
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  5. Article ; Online: Muscle matters--dendrites grow up.

    Fargo, Keith N / Foecking, Eileen M / Jones, Kathryn J

    Endocrinology

    2011  Volume 152, Issue 2, Page(s) 346–348

    MeSH term(s) Animals ; Dendrites/genetics ; Dendrites/metabolism ; Humans ; Male ; Motor Neurons/cytology ; Motor Neurons/metabolism ; Muscle, Skeletal/metabolism ; Organ Size/genetics ; Organ Size/physiology ; Rats ; Rats, Sprague-Dawley ; Rats, Transgenic ; Receptors, Androgen/genetics ; Receptors, Androgen/metabolism ; Seminal Vesicles/metabolism
    Chemical Substances Receptors, Androgen
    Language English
    Publishing date 2011-02
    Publishing country United States
    Document type Comment ; News
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/en.2010-1413
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  6. Article: Androgenic, but not estrogenic, protection of motoneurons from somal and dendritic atrophy induced by the death of neighboring motoneurons.

    Fargo, Keith N / Sengelaub, Dale R

    Developmental neurobiology

    2007  Volume 67, Issue 8, Page(s) 1094–1106

    Abstract: Motoneuron loss is a significant medical problem, capable of causing severe movement disorders or even death. We have been investigating the effects of motoneuron loss on surviving motoneurons in a lumbar motor nucleus, the spinal nucleus of the ... ...

    Abstract Motoneuron loss is a significant medical problem, capable of causing severe movement disorders or even death. We have been investigating the effects of motoneuron loss on surviving motoneurons in a lumbar motor nucleus, the spinal nucleus of the bulbocavernosus (SNB). SNB motoneurons undergo marked dendritic and somal atrophy following the experimentally induced death of other nearby SNB motoneurons. However, treatment with testosterone at the time of lesioning attenuates this atrophy. Because testosterone can be metabolized into the estrogen estradiol (as well as other physiologically active steroid hormones), it was unknown whether the protective effect of testosterone was an androgen effect, an estrogen effect, or both. In the present experiment, we used a retrogradely transported neurotoxin to kill the majority of SNB motoneurons on one side of the spinal cord only in adult male rats. Some animals were also treated with either testosterone, the androgen dihydrotestosterone (which cannot be converted into estradiol), or the estrogen estradiol. As seen previously, partial motoneuron loss led to reductions in soma area and in dendritic length and extent in surviving motoneurons. Testosterone and dihydrotestosterone attenuated these reductions, but estradiol had no protective effect. These results indicate that the neuroprotective effect of testosterone on the morphology of SNB motoneurons following partial motoneuron depletion is an androgen effect rather than an estrogen effect.
    MeSH term(s) Animals ; Atrophy ; Cell Death ; Dendrites/drug effects ; Dendrites/pathology ; Dihydrotestosterone/pharmacology ; Estradiol/pharmacology ; Male ; Motor Neurons/cytology ; Motor Neurons/drug effects ; Motor Neurons/pathology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord/cytology ; Spinal Cord/drug effects ; Spinal Cord/pathology ; Testosterone/pharmacology
    Chemical Substances Dihydrotestosterone (08J2K08A3Y) ; Testosterone (3XMK78S47O) ; Estradiol (4TI98Z838E)
    Language English
    Publishing date 2007-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2256184-5
    ISSN 1097-4695 ; 1932-8451 ; 0022-3034
    ISSN (online) 1097-4695
    ISSN 1932-8451 ; 0022-3034
    DOI 10.1002/dneu.20454
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  7. Article ; Online: Outcomes of endoscopy and computed tomography in patients with chronic rhinosinusitis.

    Amine, Muhamad / Lininger, Lauren / Fargo, Keith N / Welch, Kevin C

    International forum of allergy & rhinology

    2013  Volume 3, Issue 1, Page(s) 73–79

    Abstract: ... have resulted in a reduction in the number of CTs by 69%, resulting in an acceptable 10% (n = 24/244 ... false negative rate and 8% (n = 20/244) false positive rate.: Conclusion: Incorporating number ...

    Abstract Background: Chronic rhinosinusitis (CRS) is a common disease diagnosed based on a combination of symptoms, imaging, and/or endoscopy. Computed tomography (CT) is the gold standard in diagnosis of CRS due to inherent low sensitivity of endoscopy. We sought to assess the correlation between symptoms, endoscopy, and imaging in order to reduce the number of CTs without decreasing diagnostic accuracy.
    Methods: Retrospective review of a single practitioner's patients from 2008 to 2010 who presented for evaluation of CRS. Data on demographics, symptoms, and endoscopic and CT findings were collected and analyzed. Exclusion criteria included patients with prior surgery, no imaging, and those that failed to meet the 2007 CRS Task Force symptom criteria.
    Results: A total of 244 patients met the Task Force symptom criteria. Using CT as the gold standard, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of endoscopy alone was 36%, 95%, 89%, and 55%, respectively. The number of symptoms (NOS) strongly correlated with the absence or presence of disease (p < 0.01). Incorporating NOS into a CRS diagnostic algorithm improved sensitivity and NPV of nasal endoscopy to 82% and 79% while maintaining its specificity and PPV at 82% and 84%, respectively. Applying our algorithm retrospectively would have resulted in a reduction in the number of CTs by 69%, resulting in an acceptable 10% (n = 24/244) false negative rate and 8% (n = 20/244) false positive rate.
    Conclusion: Incorporating number of symptoms in a CRS diagnostic algorithm may drastically reduce the number of CTs needed. Clinical diagnostic accuracy is enhanced with this new algorithm while significantly reducing the cost and radiation burden of CTs.
    MeSH term(s) Algorithms ; Chronic Disease ; Endoscopy/standards ; Female ; Humans ; Male ; Middle Aged ; Reproducibility of Results ; Retrospective Studies ; Rhinitis/diagnosis ; Rhinitis/diagnostic imaging ; Sensitivity and Specificity ; Sinusitis/diagnosis ; Sinusitis/diagnostic imaging ; Tomography, X-Ray Computed/standards
    Language English
    Publishing date 2013-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2625826-2
    ISSN 2042-6984 ; 2042-6976
    ISSN (online) 2042-6984
    ISSN 2042-6976
    DOI 10.1002/alr.21071
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  8. Article ; Online: Validation of online functional measures in cognitively impaired older adults.

    Nosheny, Rachel L / Camacho, Monica R / Jin, Chengshi / Neuhaus, John / Truran, Diana / Flenniken, Derek / Ashford, Miriam / Carrillo, Maria C / Fargo, Keith N / Hendrix, James / Hanna, Lucy / Rabinovici, Gil / Maruff, Paul / Mackin, R Scott / Weiner, Michael W

    Alzheimer's & dementia : the journal of the Alzheimer's Association

    2020  Volume 16, Issue 10, Page(s) 1426–1437

    Abstract: Introduction: Assessment of functional status is associated with risk of cognitive decline and diagnosis of dementia, and can be assessed by participants and study partners (SPs).: Methods: In 770 older adults enrolled in the Imaging Dementia- ... ...

    Abstract Introduction: Assessment of functional status is associated with risk of cognitive decline and diagnosis of dementia, and can be assessed by participants and study partners (SPs).
    Methods: In 770 older adults enrolled in the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study and the online Brain Health Registry (BHR), we estimated associations between online assessments and clinical variables related to Alzheimer's disease (AD) risk.
    Results: Worse online learning scores and SP-reported functional decline were associated with higher probability of AD dementia diagnosis and poor in-clinic cognitive assessment, and with higher odds of amyloid beta (Aβ) positivity when combined with participants' report of less decline. SP report of functional decline conferred predictive value independent of online cognitive assessments. Participants underreported decline compared to SPs.
    Discussion: The results support the validity of online assessments and their greater utilization in healthcare and research settings. Online SP-reported functional decline is an indicator of dementia and AD risk.
    MeSH term(s) Aged ; Aged, 80 and over ; Cognitive Dysfunction/diagnosis ; Dementia/diagnosis ; Female ; Humans ; Male ; Neuropsychological Tests ; Online Systems
    Language English
    Publishing date 2020-07-27
    Publishing country United States
    Document type Journal Article ; Multicenter Study ; Observational Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Validation Study
    ZDB-ID 2211627-8
    ISSN 1552-5279 ; 1552-5260
    ISSN (online) 1552-5279
    ISSN 1552-5260
    DOI 10.1002/alz.12138
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  9. Article ; Online: Neuroprotective effect of testosterone treatment on motoneuron recruitment following the death of nearby motoneurons.

    Fargo, Keith N / Foster, Allison M / Sengelaub, Dale R

    Developmental neurobiology

    2009  Volume 69, Issue 12, Page(s) 825–835

    Abstract: Motoneuron loss is a significant medical problem, capable of causing severe movement disorders or even death. We have previously shown that motoneuron death induces marked dendritic atrophy in surviving nearby motoneurons. Additionally, in quadriceps ... ...

    Abstract Motoneuron loss is a significant medical problem, capable of causing severe movement disorders or even death. We have previously shown that motoneuron death induces marked dendritic atrophy in surviving nearby motoneurons. Additionally, in quadriceps motoneurons, this atrophy is accompanied by decreases in motor nerve activity. However, treatment with testosterone partially attenuates changes in both the morphology and activation of quadriceps motoneurons. Testosterone has an even larger neuroprotective effect on the morphology of motoneurons of the spinal nucleus of the bulbocavernosus (SNB), in which testosterone treatment can completely prevent dendritic atrophy. The present experiment was performed to determine whether the greater neuroprotective effect of testosterone on SNB motoneuron morphology was accompanied by a greater neuroprotective effect on motor activation. Right side SNB motoneurons were killed by intramuscular injection of cholera toxin-conjugated saporin in adult male Sprague-Dawley rats. Animals were either given Silastic testosterone implants or left untreated. Four weeks later, left side SNB motor activation was assessed with peripheral nerve recording. The death of right side SNB motoneurons resulted in several changes in the electrophysiological response properties of surviving left side SNB motoneurons, including decreased background activity, increased response latency, increased activity duration, and decreased motoneuron recruitment. Treatment with exogenous testosterone attenuated the increase in activity duration and completely prevented the decrease in motoneuron recruitment. These data provide a functional correlate to the known protective effects of testosterone treatment on the morphology of these motoneurons, and further support a role for testosterone as a therapeutic agent in the injured nervous system.
    MeSH term(s) Animals ; Atrophy ; Cell Death ; Electric Stimulation ; Electrophysiology ; Male ; Motor Neurons/drug effects ; Motor Neurons/physiology ; Muscle, Skeletal/drug effects ; Rats ; Rats, Sprague-Dawley ; Recruitment, Neurophysiological/drug effects ; Recruitment, Neurophysiological/physiology ; Signal Processing, Computer-Assisted ; Testosterone/pharmacology
    Chemical Substances Testosterone (3XMK78S47O)
    Language English
    Publishing date 2009-08-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2256184-5
    ISSN 1932-846X ; 1097-4695 ; 1932-8451 ; 0022-3034
    ISSN (online) 1932-846X ; 1097-4695
    ISSN 1932-8451 ; 0022-3034
    DOI 10.1002/dneu.20743
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  10. Article: Exogenous testosterone prevents motoneuron atrophy induced by contralateral motoneuron depletion.

    Fargo, Keith N / Sengelaub, Dale R

    Journal of neurobiology

    2004  Volume 60, Issue 3, Page(s) 348–359

    Abstract: Gonadal steroids exhibit neuroprotective and neurotherapeutic effects. The lumbar spinal cord of male rats contains a highly androgen-sensitive population of motoneurons, the spinal nucleus of the bulbocavernosus (SNB), whose morphology and function are ... ...

    Abstract Gonadal steroids exhibit neuroprotective and neurotherapeutic effects. The lumbar spinal cord of male rats contains a highly androgen-sensitive population of motoneurons, the spinal nucleus of the bulbocavernosus (SNB), whose morphology and function are dependent on testosterone in adulthood. Unilateral SNB motoneuron depletion induces dendritic atrophy in contralateral SNB motoneurons, but this atrophy is reversed in previously castrated males treated with testosterone. In the present experiment we test the hypothesis that the morphology of SNB motoneurons is protected from atrophy after contralateral motoneuron depletion by exogenous testosterone alone (i.e., with no delay between castration and testosterone replacement). We unilaterally depleted SNB motoneurons by intramuscular injection of cholera toxin conjugated saporin. Simultaneously, some saporin-injected rats were castrated and immediately given replacement testosterone. Four weeks later, contralateral SNB motoneurons were labeled with cholera toxin conjugated HRP, soma sizes were measured, and dendritic arbors were reconstructed. Contralateral SNB motoneuron depletion induced somal atrophy and dendritic retraction, but testosterone treatment prevented both of these effects. Thus, the presence of high-normal levels of testosterone prevents motoneuron atrophy induced by contralateral motoneuron depletion. These data support a therapeutic role for testosterone in preventing atrophy induced by motoneuron injury.
    MeSH term(s) Animals ; Atrophy/prevention & control ; Cell Count/methods ; Cell Size/drug effects ; Cholera Toxin/toxicity ; Dendrites/drug effects ; Functional Laterality/physiology ; Histocytochemistry/methods ; Lumbosacral Region/anatomy & histology ; Male ; Motor Neurons/drug effects ; Motor Neurons/pathology ; Muscle, Skeletal/physiology ; Orchiectomy/methods ; Organ Size/drug effects ; Plant Proteins/toxicity ; Rats ; Rats, Sprague-Dawley ; Ribosome Inactivating Proteins, Type 1 ; Spinal Cord/cytology ; Testosterone/pharmacology ; Testosterone/therapeutic use ; Time Factors
    Chemical Substances Plant Proteins ; Ribosome Inactivating Proteins, Type 1 ; cholera toxin B-saporin conjugate ; Testosterone (3XMK78S47O) ; Cholera Toxin (9012-63-9)
    Language English
    Publishing date 2004-09-05
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 300903-8
    ISSN 1097-4695 ; 0022-3034
    ISSN (online) 1097-4695
    ISSN 0022-3034
    DOI 10.1002/neu.20027
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