bluuebunny/crossref_metadata_2025_split huggingface dataset:
Facilitation of fear extinction by the 5‐HT1A receptor agonist tandospirone: Possible involvement of dopaminergic modulation
Authors: Saito Yasuhiro , Matsumoto Machiko , Yanagawa Yoshiki , Hiraide Sachiko , Inoue Sumiyoshi , Kubo Yasunori , Shimamura Kei‐Ichi , Togashi Hiroko 
Published: November 2012

AbstractFear extinction‐based exposure treatment is an important component of psychotherapy for anxiety disorders such as posttraumatic stress disorder (PTSD). Recent studies have focused on pharmacological approaches combined with exposure therapy to augment extinction. In this study, we elucidated the therapeutic potential of the serotonin 1A (5‐HT1A) receptor agonist tandospirone compared with the effects of the N‐methyl‐D‐aspartate partial agonist D‐cycloserine (DCS), focusing on the possible involvement of dopaminergic mechanisms. We used a rat model of juvenile stress [aversive footshock (FS)] exposure during the third postnatal week (3wFS). The 3wFS group exhibited extinction deficit reflected in sustained fear‐related behavior and synaptic dysfunction in the hippocampal CA1 field and medial prefrontal cortex (mPFC), which are responsible for extinction processes. Tandospirone administration (5 mg/kg, i.p.) before and after the extinction trials ameliorated both the behavioral deficit and synaptic dysfunction, i.e., synaptic efficacy in the CA1 field and mPFC associated with extinction training and retrieval, respectively, was potentiated in the tandospirone‐treated 3wFS group. Extracellular dopamine release in the mPFC was increased by extinction retrieval in the non‐FS control group. This facilitation was not observed in the 3wFS group; however, tandospirone treatment increased cortical dopamine levels after extinction retrieval. DCS (15 mg/kg, i.p.) also ameliorated the extinction deficit in the 3wFS group, but impaired extinction in the non‐FS control group. These results suggest that tandospirone has therapeutic potential for enhancing synaptic efficacy associated with extinction processes by involving dopaminergic mechanisms. Pharmacological agents that target cortical dopaminergic systems may provide new insights into the development of therapeutic treatments of anxiety disorders, including PTSD. © Synapse, 2013. © 2012 Wiley Periodicals, Inc.
Columnar distribution of catecholaminergic neurons in the ventrolateral periaqueductal gray and their relationship to efferent pathways
Authors: Suckow Shelby K. , Deichsel Emily L. , Ingram Susan L. , Morgan Michael M. , Aicher Sue A. 
Published: November 2012

AbstractThe periaqueductal gray (PAG) is a critical brain region involved in opioid analgesia and provides efferents to descending pathways that modulate nociception. In addition, the PAG contains ascending pathways to regions involved in the regulation of reward, including the substantia nigra (SN) and the ventral tegmental area (VTA). SN and VTA contain dopaminergic neurons that are critical for the maintenance of positive reinforcement. Interestingly, the PAG is also reported to contain a population of dopaminergic neurons. In this study, the distribution of catecholaminergic neurons within the ventrolateral (vl) PAG was examined using immunocytochemical methods. In addition, the catecholaminergic PAG neurons were examined to determine whether these neurons are integrated into ascending (VTA, SN) and descending rostral ventral medulla (RVM) efferent pathways from this region. The immunocytochemical analysis determined that catecholaminergic neurons in the PAG are both dopaminergic and noradrenergic and these neurons have a distinct rostrocaudal distribution within the ventrolateral column of PAG. Dopaminergic neurons were concentrated rostrally and were significantly smaller than noradrenergic neurons. Combined immunocytochemistry and tract tracing methods revealed that catecholaminergic neurons are distinct from, but closely associated with, both ascending and descending efferent projection neurons. Finally, by electron microscopy, catecholaminergic neurons showed close dendritic appositions with other neurons in PAG, suggesting a possible nonsynaptic mechanism for regulation of PAG output by these neurons. In conclusion, our data indicate that there are two populations of catecholaminergic neurons in the vlPAG that form dendritic associations with both ascending and descending efferents suggesting a possible nonsynaptic modulation of vlPAG neurons. Synapse, 2013. © 2012 Wiley Periodicals, Inc.
In vitro binding of a radio‐labeled positive allosteric modulator for metabotropic glutamate receptor subtype 5
Authors: Zysk John R. , Spear Nathan , Fieles William , Stein Mark M. , Sygowski Linda S. , King Megan M. , Hoesch Valerie , Hastings Richard , Brockel Becky , Do Mylinh , Ström Peter , Gadient Reto , Chhajlani Vijay , Elmore Charles S. , Maier Donna L 
Published: November 2012

AbstractThe positive allosteric modulator (PAM) binding site for metabotropic glutamate receptor subtype 5 (mGlu5) lacks a readily available radio‐labeled tracer fordetailed structure‐activity studies. This communication describes a selective mGlu5 compound, 7‐methyl‐2‐(4‐(pyridin‐2‐yloxy)benzyl)‐5‐(pyridin‐3‐yl)isoindolin‐1‐one (PBPyl) that binds with high affinity to human mGlu5 and exhibits functional PAM activity. Analysis of PBPyl by FLIPR revealed an EC50 of 87 nM with an 89% effect in transfected HEK293 cells and an EC50 of 81 nM with a 42% effect in rat primary neurons. PBPyl exhibited 5‐fold higher functional selectivity for mGlu5 in a full mGlu receptor panel. Unlabeled PBPyl was tested for specific binding using a liquid chromatography mass spectrometry (LC/MS/MS)‐based filtration binding assay and exhibited 40% specific binding in recombinant membranes, a value higher than any candidate compound tested. In competition binding studies with [3H]MPEP, the mGlu5 receptor negative allosteric modulator (NAM), PBPyl exhibited a k
i value of 34 nM. PBPyl also displaced [3H]ABP688, a mGluR5 receptor NAM, in tissue sections from mouse and rat brain using autoradiography. Areas of specific binding included the frontal cortex, striatum and nucleus accumbens. PBPyl was radiolabeled to a specific activity of 15 Ci/mmol and tested for specific binding in a filter plate format. In recombinant mGlu5b membranes, [3H] PBPyl exhibited saturable binding with a Kd value of 18.6 nM. In competition binding experiments, [3H] PBPyl was displaced by high affinity mGlu5 positive and negative modulators. Further tests showed that PBPyl displays less than optimal characteristics as an in vivo tool, including a high volume of distribution and ClogP, making it more suitable as an in vitro compound. However, as a first report of direct binding of an mGlu5 receptor PAM, this study offers value toward the development of novel PET imaging agents for this important therapeutic target. Synapse, 2013. © 2012 Wiley Periodicals, Inc.
Periventricular nodular heterotopia on prenatal ultrasound and magnetic resonance imaging
Authors: Blondiaux E. , Sileo C. , Nahama‐Allouche C. , Moutard M. L. , Gelot A. , Jouannic J. M. , Ducou le Pointe H. , Garel C. 
Published: November 2012

ABSTRACTObjectivesTo describe the prenatal ultrasound and magnetic resonance imaging (MRI) findings suggestive of periventricular nodular heterotopia (PNH).MethodsThis retrospective case series included fetuses referred to our institution for brain MRI between 2007 and 2012, which were diagnosed with PNH and confirmed by postnatal MRI or autopsy. The type of PNH, associated ventriculomegaly and associated malformations are reported.ResultsWe included 11 fetuses (nine female, two male) with a mean gestational age at diagnosis of 31 (range, 23–34) weeks. PNH lesions were small and diffuse (n = 7), large and multiple (n = 1) or single (n = 3). A targeted ultrasound examination performed before fetal MRI missed the diagnosis in four cases (one diffuse and three single); a further ultrasound examination performed after MRI diagnosed PNH in two of these four cases. Ventriculomegaly was present in six cases (four unilateral and two bilateral). PNH appeared in all cases as nodules of intermediate echogenicity protruding into the ventricular lumen. In all cases of diffuse PNH, the frontal horns and bodies of the lateral ventricles appeared square in shape on coronal view, with irregular borders on axial view. Associated cerebral malformations were observed in seven cases and included corpus callosal agenesis (n = 4, with additional malformations in two) and retrocerebellar cyst (n = 3). Extracerebral malformations were also present in two cases. Maternal MRI was performed in five of the six cases of isolated small and diffuse PNH in female fetuses, and demonstrated PNH in two of these.ConclusionPNH is underdiagnosed at prenatal ultrasound, even on targeted scans. Irregular ventricular borders on axial view and irregular square‐shaped lateral ventricles on coronal view are suggestive of PNH at prenatal ultrasound. Copyright © 2012 ISUOG. Published by John Wiley & Sons Ltd.
Evaluation of cervical stiffness during pregnancy using semiquantitative ultrasound elastography
Authors: Hernandez‐Andrade E. , Hassan S. S. , Ahn H. , Korzeniewski S. J. , Yeo L. , Chaiworapongsa T. , Romero R. 
Published: November 2012

ABSTRACTObjectiveTo evaluate cervical stiffness during pregnancy using ultrasound‐derived elastography, a method used to estimate the average tissue displacement (strain) within a defined region of interest when oscillatory compression is applied.MethodsStrain was calculated in two regions of interest, the endocervical canal and the entire cervix, from three anatomical planes of the cervix: mid‐sagittal in the plane used for cervical length measurement and in cross‐sectional planes located at the internal and external cervical os. Associations between strain values, method of ascertainment and patient characteristics were assessed using linear mixed models to account for within‐subject correlation. Inter‐rater agreement in defining the degree of cervical stiffness was evaluated in 120 regions of interest acquired by two operators in 20 patients.ResultsA total of 1557 strain estimations were performed in 262 patients at 8–40 weeks of gestation. Adjusting for other sources of variation, (1) cervical tissue strain estimates obtained in the endocervical canal were on average 33% greater than those obtained in the entire cervix; (2) measurements obtained in the cross‐sectional plane of the external cervical os and sagittal plane were 45% and 13% greater than those measured in the cross‐sectional plane of the internal cervical os, respectively; (3) mean strain rates were 14% and 5% greater among parous women with and without a history of preterm delivery compared with those of nulliparous women, respectively, and were on average 13% greater among women with a cervical length of between 25 and 30 mm compared to those with a cervical length of > 30 mm; and (4) cervical tissue strain was more strongly associated with cervical length than with gestational age.ConclusionSemiquantitative elastography can be employed to evaluate changes in cervical stiffness during pregnancy.
Intermittent, moderate-intensity aerobic exercise for only eight weeks reduces arterial stiffness: evaluation by measurement of stiffness parameter and pressure–strain elastic modulus by use of ultrasonic echo tracking
Authors: Tanaka Midori , Sugawara Motoaki , Ogasawara Yasuo , Izumi Tadafumi , Niki Kiyomi , Kajiya Fumihiko 
Published: November 2012

Abstract

Background and purpose
Aerobic exercise has been reported to be associated with reduced arterial stiffness. However, the intensity, duration, and frequency of aerobic exercise required to improve arterial stiffness have not been established. In addition, most reports base their conclusions on changes in pulse wave velocity, which is an indirect index of arterial stiffness. We studied the effects of short-term, intermittent, moderate-intensity exercise training on arterial stiffness based on measurements of the stiffness parameter (β) and pressure–strain elastic modulus (E
p), which are direct indices of regional arterial stiffness.

Methods
A total of 25 young healthy volunteers (18 men) were recruited. By use of ultrasonic diagnostic equipment we measured β and E
p of the carotid artery before and after 8 weeks of exercise training.

Results
After exercise training, systolic pressure (P
s), diastolic pressure (P
d), pulse pressure, systolic arterial diameter (D
s), and diastolic arterial diameter (D
d) did not change significantly. However, the pulsatile change in diameter ((D
s − D
d)/D
d) increased significantly, and β and E
p decreased significantly.

Conclusions
For healthy young subjects, β and E
p were reduced by intermittent, moderate-intensity exercise training for only 8 weeks.
The Predictive Validity of Subjective Mortality Expectations: Evidence From the Health and Retirement Study
Authors: Elder Todd E. 
Published: November 2012

Abstract
Several recent studies suggest that individual subjective survival forecasts are powerful predictors of both mortality and behavior. Using 15 years of longitudinal data from the Health and Retirement Study, I present an alternative view. Across a wide range of ages, predictions of in-sample mortality rates based on subjective forecasts are substantially less accurate than predictions based on population life tables. Subjective forecasts also fail to capture fundamental properties of senescence, including increases in yearly mortality rates with age. To shed light on the mechanisms underlying these biases, I develop and estimate a latent-factor model of how individuals form subjective forecasts. The estimates of this model’s parameters imply that these forecasts incorporate several important sources of measurement error that arguably swamp the useful information they convey.
Short‐ versus long‐term prediction of dementia among subjects with low and high educational levels
Authors: Chary Emilie , Amieva Hélène , Pérès Karine , Orgogozo Jean‐Marc , Dartigues Jean‐François , Jacqmin‐Gadda Hélène 
Published: November 2012

AbstractBackgroundUsing simple measures of cognition and disability in a prospective community‐living cohort of normal elderly persons, the main objectives of our study were to distinguish short‐ and long‐term predictors for dementia according to educational level and to propose a tool for early detection of subjects at high risk of dementia.MethodsData derived from the French cohort study Paquid (Personnes Agées QUID), which included 3777 subjects, older than 65 years of age, who were followed for a 20‐year period. The risk of dementia at 3 years and 10 years was estimated by logistic regression for repeated measures combining data from all the 3‐ and 10‐year windows throughout the follow‐up. Predictors included disability assessed by the number of dependent items among four instrumental activities of daily living (IADLs), four neuropsychological tests, five Mini‐Mental State Examination (MMSE) subtests, and four items of subjective memory complaints.ResultsOf the 2882 included subjects, the number of IADLs remained a predictor of short‐ and long‐term conversion to dementia for those with low educational level (combined with only one cognitive test) whereas the best predictors for more educated subjects combined subjective memory complaints and memory and executive function tests. The episodic memory subtest was the only predictive MMSE subtest. In the high‐education‐level group, the areas under the receiver–operating characteristic curve of the selected models were 0.85 for 3‐year prediction and 0.78 for 10‐year prediction.ConclusionEarly predictors of dementia are different according to educational level. Among subjects reaching the secondary school level, early detection of those at high risk of dementia is possible with good predictive performance, with a few simple objective and subjective cognitive evaluations.
Intracerebral propagation of Alzheimer's disease: Strengthening evidence of a herpes simplex virus etiology
Authors: Ball Melvyn J. , Lukiw Walter J. , Kammerman Eli M. , Hill James M. 
Published: November 2012

BackgroundA faulty human protein, abnormally phosphorylated tau, was recently publicized to spread “like a virus” from neuron to neuron in Alzheimer's patients’ brains. For several decades, we have been amassing arguments showing that herpes simplex virus type 1 (HSV‐1), not p‐tau, propagates this interneuronal, transsynaptic pathologic cascade.MethodsWe reiterate convincing data from our own (and other) laboratories, reviewing the first anatomic foothold neurofibrillary tangles gain in brainstem and/or entorhinal cortex; the chronic immunosurveillance cellularity of the trigeminal ganglia wherein HSV‐1 awakens from latency to reactivate; the inabilities of p‐tau protein's physical properties to promote it to jump synapses; the amino acid homology between human p‐tau and VP22, a key target for phosphorylation by HSV serine/threonine–protein kinase UL13; and the exosomic secretion of HSV‐1–infected cells’ L‐particles, attesting to the cell‐to‐cell passage of microRNAs of herpesviruses.ResultsThe now‐maturing construct that reactivated HSV‐1 best accounts for the intracerebral propagation of AD changes in the human brain should at last seem highly attractive. This hypothesis might even explain statins' apparent mechanism in some studies for lowering AD incidence.ConclusionProvided that funding agencies will quickly ignite a new realm of investigation, the rejuvenated enthusiasm for testing this optimistic construct holds incalculable potential for rapid, efficacious clinical application, through already available and relatively safe antiviral therapeutics.
Factors Associated With Home Discharge After Rehabilitation Among Male Veterans With Lower Extremity Amputation
Authors: Kurichi Jibby E. , Ripley Diane Cowper , Xie Dawei , Kwong Pui L. , Bates Barbara E. , Stineman Margaret G. 
Published: November 2012

ObjectiveTo determine the patient‐, treatment‐, and facility‐level factors that are associated with home discharge among male veterans with lower extremity amputation who received inpatient rehabilitation after surgery.DesignA retrospective observational study.SettingVeterans Affairs Medical Centers.ParticipantsThis study included 1480 male veterans.MethodsGeneralized estimating equation models were used to model the likelihood of home discharge to account for within‐facility clustering. We reported odds ratios (ORs) and 95% confidence intervals (95% CIs).Main Outcome MeasurementDischarged to home.ResultsThere were a total of 1163 (78.6%) veterans who were discharged home after the surgical hospitalization, compared with other locations. Patients who were married were more likely to be discharged home compared with patients who were not married (OR = 1.51, 95% CI = 1.14‐1.99, P < .01). Compared with being transferred from another hospital or extended care, patients who were admitted from home were far more likely to be discharged home (OR = 8.43, 95% CI = 5.48‐12.96, P < .0001). Patients with evidence of local significant infection were less likely to be discharged home (OR = 0.57, 95% CI = 0.39‐0.83, P < .01), as were patients with evidence of congestive heart failure (OR = 0.62, 95% CI = 0.45‐0.85, P < .01) or depression (OR = 0.63, 95% CI = 0.40‐0.98, P = .04). Veterans with greater discharge motor Functional Independence Measure scores were more likely to be discharged home (OR = 1.23, 95% CI = 1.16‐1.31 per 10‐point increase in discharge Functional Independence Measure motor score, P < .0001). Conversely, patients undergoing procedures for ongoing active cardiac pathology were less likely to be discharged home (OR = 0.55, 95% CI = 0.37‐0.81, P < .01).ConclusionsThis study showed a strong association between the sociological factors of marital status and living location before hospitalization and home discharge. The significance of discharge functional status highlights the importance of addressing the expected care burden once patients are discharged home.
Designing and Implementing a System for Tracking Functional Status After Stroke: A Feasibility Study
Authors: Sandel M. Elizabeth , Jette Alan M. , Appelman Jed , Terdiman Joseph , TeSelle Marian , Delmonico Richard L. , Wang Hua , Camicia Michelle , Rasch Elizabeth K. , Brandt Diane E. , Chan Leighton 
Published: November 2012

ObjectiveTo determine the feasibility of tracking stroke patients' functional outcomes in an integrated health system across a care continuum using the computer version of the Activity Measure of Post‐Acute Care (AM‐PAC).SettingA large integrated health care system in northern California.ParticipantsA total of 222 stroke patients (aged ≥18 years) who were hospitalized after an acute cerebrovascular accident.MethodsAn AM‐PAC assessment was made at discharge from sites of care, including acute hospital, inpatient rehabilitation hospital, skilled nursing facility, home during home care, and outpatient settings. Assessments also were completed in the patient's home at 6 months. Data from the AM‐PAC program were integrated with the health care system's databases.Main Outcome Measurements(1) AM‐PAC administration time at the various sites of care; (2) assessment of a floor or a ceiling effect; and (3) administrative burden of tracking participants.ResultsAM‐PAC assessment sessions averaged 7.9 minutes for data acquisition in 3 domains: Basic Mobility, Activities of Daily Living, and Applied Cognition. Participants answered, on average, 27 AM‐PAC questions per session. A small ceiling effect was observed at 6 months, and there was a larger ceiling effect when the instrument was administered in an institution, ie, when the AM‐PAC institutional item bank was used rather than the community item bank. It was feasible to track patients and to assess their function using the AM‐PAC instrument from institutional to community settings. Implementation of the AM‐PAC in clinical environments, and the success of the project, were influenced by instrumental, technological, operational, resource, and cultural factors.ConclusionsThis study demonstrates the feasibility of implementing a single functional outcome instrument in clinical and community settings to measure rehabilitation functional outcomes of stroke patients. Integrating the AM‐PAC measurement system into clinical workflows and the electronic medical record could provide assistance to clinicians for medical decision making, functional prognostication, and discharge planning.