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1.
JDR Clin Trans Res ; 6(3): 279-290, 2021 07.
Article in English | MEDLINE | ID: mdl-33902341

ABSTRACT

BACKGROUND: The COVID-19 novel coronavirus closed oral health care in Nova Scotia (NS) Canada in March 2020. Preparing for a phased reopening, a knowledge exchange coalition (representing government, academia, hospitals, oral health professions, and regulators) developed return-to-work (RTW) guidelines detailing the augmentation of standard practices to ensure safety for patients, oral health care providers (OHPs), and the community. Using online surveys, this study explored the influence of the RTW guidelines and related education on registered NS OHPs during a phased return to work. METHODS: Dissemination of R2W guidelines included website or email communiques and interdisciplinary education webinars that coincided with 2 RTW phases approved by the government. Aligned with each phase, all registered dentists, dental hygienists, and dental assistants were invited to complete an online survey to gauge the influence of the coalition-sponsored education and RTW guidelines, confidence, preparedness, and personal protective equipment use before and after the pandemic. RESULTS: Three coalition-sponsored multidisciplinary webinars hosted 3541 attendees prior to RTW. The response to survey 1 was 41% (881/2156) and to survey 2 was 26% (571/2177) of registrants. Survey 1 (82%) and survey 2 (89%) respondents "agreed/strongly agreed" that R2W guidelines were a primary source for guiding return to practice, and most were confident with education received and had the skills needed to effectively treat patients during the COVID-19 pandemic. Confidence and preparedness improved in survey 2. Gowns/lab coat use for aerosol-generating procedures increased from 26% to 93%, and the use of full face shields rose from 6% to 93% during the pandemic. CONCLUSIONS: A multistakeholder coalition was effective in establishing and communicating comprehensive guidelines and web-based education to ensure unified reintegration of oral health services in NS during a pandemic. This multiorganizational cooperation lay the foundation for responses to subsequent waves of COVID-19 and may serve as an example for collaboratively responding to future public health threats in other settings. KNOWLEDGE TRANSFER STATEMENT: The return-to-work strategy that was developed, disseminated, and assessed through this COVID-19 knowledge exchange coalition will benefit oral health practitioners, professional regulators, government policy makers, and researchers in future pandemic planning.


Subject(s)
COVID-19 , Dental Health Services , Humans , Nova Scotia , Pandemics/prevention & control , SARS-CoV-2
3.
Clin Neuropsychol ; 33(5): 905-927, 2019 07.
Article in English | MEDLINE | ID: mdl-30472911

ABSTRACT

Objective: Medial thalamic stroke in adults commonly results in severe learning and memory impairments and executive dysfunction, particularly during the acute phase. However, there is limited research on the cognitive recovery from thalamic stroke in physically healthy adolescents. This study aimed to fill this gap in the literature by utilizing a monozygotic twin control to investigate the neuropsychological outcomes of bilateral thalamic stroke in adolescence. Method: We evaluated an otherwise healthy 17-year-old male with a history of premature birth, developmental delay, and learning disability 2 and 7 months after he sustained a bilateral medial/anterior thalamic stroke of unknown etiology. His identical twin brother served as a case control. Results: The patient presented with improvements in many cognitive skills between assessments, most notably processing speed. Despite some mild improvement, however, he presented with significant deficits in fine motor speed/coordination, spatial perception, and rapid naming. Additionally, he exhibited persistent, severe deficits in verbal learning and memory. Relative sparing of executive functions (i.e., planning and set-shifting) and attention on standardized measures in this case may be explained by good underlying health, limited extra-thalamic damage, and/or recovery of function. The effects of thalamic injury resulted in minimal adaptive dysfunction or deterrence from academic or athletic success for the presented case. Conclusions: These results suggest risk for deficits in encoding of new verbal information following bilateral thalamic stroke in adolescence, as well as risk for persistent cognitive deficits despite initial improvements. This is consistent with descriptions of anterograde memory impairments in adults with similar lesions.


Subject(s)
Neuropsychological Tests/standards , Stroke/diagnosis , Thalamus/pathology , Adolescent , Humans , Male , Stroke/pathology , Twins, Monozygotic
4.
Behav Brain Res ; 311: 192-200, 2016 09 15.
Article in English | MEDLINE | ID: mdl-27233825

ABSTRACT

A recent model by Postma and colleagues posits that the encoding of object location associations (OLAs) requires the coordination of several cognitive processes mediated by ventral (object perception) and dorsal (spatial perception) visual pathways as well as the hippocampus (feature binding) [1]. Within this model, frontoparietal network recruitment is believed to contribute to both the spatial processing and working memory task demands. The current study used functional magnetic resonance imaging (fMRI) to test each step of this model in 15 participants who encoded OLAs and performed standard n-back tasks. As expected, object processing resulted in activation of the ventral visual stream. Object in location processing resulted in activation of both the ventral and dorsal visual streams as well as a lateral frontoparietal network. This condition was also the only one to result in medial temporal lobe activation, supporting its role in associative learning. A conjunction analysis revealed areas of shared activation between the working memory and object in location phase within the lateral frontoparietal network, anterior insula, and basal ganglia; consistent with prior working memory literature. Overall, findings support Postma and colleague's model and provide clear evidence for the role of working memory during OLA encoding.


Subject(s)
Association Learning/physiology , Brain/physiology , Memory, Short-Term/physiology , Space Perception/physiology , Spatial Memory/physiology , Visual Perception/physiology , Adolescent , Adult , Brain/diagnostic imaging , Brain Mapping , Humans , Magnetic Resonance Imaging , Male , Models, Psychological , Neural Pathways/diagnostic imaging , Neural Pathways/physiology , Neuropsychological Tests , Young Adult
5.
Lupus ; 25(2): 162-76, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26391610

ABSTRACT

Patients with antiphospholipid syndrome (APS) produce antiphospholipid antibodies (aPL) and develop vascular thrombosis that may occur in large or small vessels in the arterial or venous beds. On the other hand, many individuals produce aPL and yet never develop thrombotic events. Toll-like receptor 4 (TLR4) appears to be necessary for aPL-mediated prothrombotic effects in venous and microvascular models of thrombosis, but its role in arterial thrombosis has not been studied. Here, we propose that aPL alone are insufficient to cause thrombotic events in an arterial model of APS, and that a concomitant trigger of innate immunity (e.g. TLR4 activation) is required. We show specifically that anti-ß2-glycoprotein I (anti-ß2GPI) antibodies, a subset of aPL, accelerated thrombus formation in C57BL/6 wild-type, but not TLR4-deficient, mice in a ferric chloride-induced carotid artery injury model. These aPL bound to arterial and venous endothelial cells, particularly in the presence of ß2GPI, and to human TLR4 by enzyme-linked immunoassay. Arterial endothelium from aPL-treated mice had enhanced leukocyte adhesion, compared to control IgG-treated mice. In addition, aPL treatment of mice enhanced expression of tissue factor (TF) in leukocytes induced by the TLR4 ligand lipopolysaccharide (LPS). aPL also enhanced LPS-induced TF expression in human leukocytes in vitro. Our findings support a mechanism in which aPL enhance TF expression by leukocytes, as well as augment adhesion of leukocytes to the arterial endothelium. The activation of TLR4 in aPL-positive individuals may be required to trigger thrombotic events.


Subject(s)
Antibodies, Antiphospholipid/immunology , Thrombosis/immunology , Toll-Like Receptor 4/immunology , Animals , Antibodies, Monoclonal, Murine-Derived/immunology , Antiphospholipid Syndrome/immunology , Cell Adhesion/physiology , Endothelium, Vascular/metabolism , Female , Humans , Immunity, Innate , Leukocytes/immunology , Lipopolysaccharides/immunology , Mice , Mice, Inbred C57BL , Models, Biological , Thromboplastin/immunology , beta 2-Glycoprotein I/antagonists & inhibitors , beta 2-Glycoprotein I/immunology
6.
Behav Brain Res ; 283: 191-5, 2015 Apr 15.
Article in English | MEDLINE | ID: mdl-25647757

ABSTRACT

Two forms of spatial processing are involved in object location memory. Coordinate processing uses a fine-grained code to provide exact knowledge for the location and is believed dependent on the right posterior parietal cortex (PPC). Categorical processing relies on spatial relationships between objects and is believed dependent on the left PPC. We used transcranial direct current stimulation (tDCS) to test these brain-behavior relationships during the encoding and subsequent recall of object location associations. Twelve right-handed, healthy young participants received 20 min of tDCS (2mA) during three separate sessions. Stimulation delivery was counterbalanced across participants and sessions and included anodal ("excitatory") stimulation of right PPC with concurrent left PPC cathodal ("inhibitory") stimulation (R+L-), the reverse montage (R-L+), and sham stimulation. Participants completed different versions of the Object Location Touchscreen Task (OLTT) during each session, which assesses coordinate (recall of the location without the environment) and categorical processing (recall of the location with the environment). Encoding occurred during the last 5 min of stimulation, while the delay phase occurred 15 min after stimulation. Participants performed more accurately during the coordinate phase following R-L+ stimulation when compared to R+L- performance. Categorical performance was not significantly affected by stimulation. Findings suggest two possibilities that will be examined in future studies with larger sample sizes: (1) The R-L+ facilitates left-hemisphere dominant categorical processing, the benefits of which persists even when environmental details are absent, possibly due to increased mental imagery; (2) Cathodal stimulation decreased spurious neuronal noise thereby allowing for more efficient processing by the "critical" neuronal populations in the right PPC.


Subject(s)
Parietal Lobe/physiology , Spatial Memory/physiology , Transcranial Direct Current Stimulation/methods , Adolescent , Adult , Cross-Over Studies , Functional Laterality , Humans , Mental Recall/physiology , Neuropsychological Tests , Single-Blind Method , Transcranial Direct Current Stimulation/adverse effects , Visual Perception/physiology , Young Adult
7.
Brain Imaging Behav ; 9(4): 801-20, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25481386

ABSTRACT

Traumatic brain injury (TBI) survivors typically exhibit significant learning and memory deficits and also frequently demonstrate hyperactivation during functional magnetic resonance imaging (fMRI) tasks involving working memory encoding and maintenance. However, it remains unclear whether the hyperactivation observed during such working memory tasks is also present during long-term memory encoding. The preliminary experiments presented here were designed to examine this question. In Experiment 1, 7 healthy controls (HC) and 7 patients with moderate to severe TBI encoded ecologically relevant object location associations (OLA) while undergoing fMRI and then completed a memory test outside of the fMRI environment. fMRI data analysis included only the correctly encoded trials and revealed hyperactivation in the TBI relative to HC group in regions critical for OLA encoding, including bilateral dorsal and ventral visual processing areas, bilateral frontoparietal working memory network regions, and the left medial temporal lobe. There was also an incidental finding that this hyperactivation persisted after multiple exposures to the same stimulus, which may indicate an attenuated repetition suppression effect that could ultimately contribute to cognitive fatigue and inefficient memory encoding after TBI. Experiment 2 directly assessed repetition suppression in some of the same HC and TBI participants. During early encoding trials, the TBI group showed large areas of hyperactivation in the right prefrontal cortex and bilateral posterior parietal cortices relative to the HC. Following additional exposure to these stimuli, the TBI group showed repetition suppression in visual and spatial processing regions, but continued to show hyperactivation in the right dorsolateral prefrontal cortex. Findings from these preliminary studies may reflect that increased reliance on cognitive control mechanisms following TBI extends to memory encoding.


Subject(s)
Brain Injuries/physiopathology , Brain Injuries/psychology , Memory/physiology , Prefrontal Cortex/physiopathology , Adolescent , Adult , Association Learning/physiology , Brain Mapping , Chronic Disease , Humans , Magnetic Resonance Imaging , Middle Aged , Neuropsychological Tests , Severity of Illness Index , Visual Perception/physiology , Young Adult
8.
Arch Clin Neuropsychol ; 29(4): 322-8, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24709384

ABSTRACT

The current study (i) determined whether NeuroQuant(®) volumetrics are reflective of differences in medial temporal lobe (MTL) volumes between healthy older adults and those with mild cognitive impairment (MCI) and (ii) examined the relationship between RBANS indices and MTL volumes. Forty-three healthy older adults and 57 MCI patients completed the RBANS and underwent structural MRI. Hippocampal and inferior lateral ventricle (ILV) volumes were obtained using NeuroQuant(®). Results revealed significantly smaller hippocampal and larger ILV volumes in MCI patients. MTL volumes were significantly related to the RBANS Immediate and Delayed Memory and Language indices but not the Attention or Visuoconstruction indices; findings that demonstrate anatomical specificity. Following discriminant function analysis, we calculated a cutpoint that may prove clinically useful for integrating MTL volumes into the diagnosis of MCI. These findings demonstrate the potential clinical utility of NeuroQuant(®) and are the first to document the relationship between RBANS indices and MTL volumes.


Subject(s)
Cognitive Dysfunction/complications , Cognitive Dysfunction/pathology , Memory Disorders/etiology , Temporal Lobe/pathology , Aged , Aged, 80 and over , Analysis of Variance , Chi-Square Distribution , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Statistics as Topic
9.
Mol Psychiatry ; 19(10): 1143-9, 2014 Oct.
Article in English | MEDLINE | ID: mdl-23999527

ABSTRACT

In 2007, a multifaceted syndrome, associated with anti-NMDA receptor autoantibodies (NMDAR-AB) of immunoglobulin-G isotype, has been described, which variably consists of psychosis, epilepsy, cognitive decline and extrapyramidal symptoms. Prevalence and significance of NMDAR-AB in complex neuropsychiatric disease versus health, however, have remained unclear. We tested sera of 2817 subjects (1325 healthy, 1081 schizophrenic, 263 Parkinson and 148 affective-disorder subjects) for presence of NMDAR-AB, conducted a genome-wide genetic association study, comparing AB carriers versus non-carriers, and assessed their influenza AB status. For mechanistic insight and documentation of AB functionality, in vivo experiments involving mice with deficient blood-brain barrier (ApoE(-/-)) and in vitro endocytosis assays in primary cortical neurons were performed. In 10.5% of subjects, NMDAR-AB (NR1 subunit) of any immunoglobulin isotype were detected, with no difference in seroprevalence, titer or in vitro functionality between patients and healthy controls. Administration of extracted human serum to mice influenced basal and MK-801-induced activity in the open field only in ApoE(-/-) mice injected with NMDAR-AB-positive serum but not in respective controls. Seropositive schizophrenic patients with a history of neurotrauma or birth complications, indicating an at least temporarily compromised blood-brain barrier, had more neurological abnormalities than seronegative patients with comparable history. A common genetic variant (rs524991, P=6.15E-08) as well as past influenza A (P=0.024) or B (P=0.006) infection were identified as predisposing factors for NMDAR-AB seropositivity. The >10% overall seroprevalence of NMDAR-AB of both healthy individuals and patients is unexpectedly high. Clinical significance, however, apparently depends on association with past or present perturbations of blood-brain barrier function.


Subject(s)
Autoantibodies/blood , Blood-Brain Barrier/metabolism , Mood Disorders/metabolism , Parkinson Disease/metabolism , Receptors, N-Methyl-D-Aspartate/immunology , Schizophrenia/metabolism , Adult , Aged , Animals , Apolipoproteins E/genetics , Apolipoproteins E/metabolism , Cerebral Cortex/metabolism , Endocytosis/physiology , Female , Genome-Wide Association Study , Humans , Influenza, Human/genetics , Influenza, Human/metabolism , Male , Mice, Inbred C57BL , Mice, Knockout , Middle Aged , Mood Disorders/genetics , Neurons/metabolism , Parkinson Disease/genetics , Polymorphism, Single Nucleotide , Receptors, N-Methyl-D-Aspartate/genetics , Schizophrenia/genetics
10.
J Int Neuropsychol Soc ; 20(2): 135-51, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24331156

ABSTRACT

Several recent reviews have suggested that cognitive rehabilitation may hold promise in the treatment of memory deficits experienced by patients with mild cognitive impairment. In contrast to the previous reviews that mainly focused on outcome, the current review examines key methodological challenges that are critical for designing and interpreting research studies and translating results into clinical practice. Using methodological details from 36 studies, we first examine diagnostic variability and how the use of cutoffs may bias samples toward more severely impaired patients. Second, the strengths and limitations of several common rehabilitative techniques are discussed. Half of the reviewed studies used a multi-technique approach that precludes the causal attribution between any specific technique and subsequent improvement. Third, there is a clear need to examine the dose-response relationship since this information was strikingly absent from most studies. Fourth, outcome measures varied widely and frequently depended on neuropsychological tests with little theoretical justification or ecological relevance. Fifth, we discuss how the variability in each of these other four areas complicates efforts to examine training generalization. Overall, future studies should place greater emphasis on ecologically relevant treatment approaches and outcome measures and we propose a hierarchical model that may aid in this pursuit.


Subject(s)
Cognitive Behavioral Therapy/methods , Cognitive Dysfunction/complications , Cognitive Dysfunction/rehabilitation , Memory Disorders/etiology , Memory Disorders/rehabilitation , Humans
11.
Genome Announc ; 1(3)2013 May 16.
Article in English | MEDLINE | ID: mdl-23682142

ABSTRACT

We report the genome sequences of four isolates of a human gut symbiont, Bifidobacterium longum. Strains 44B and 35B were isolated from two 1-year-old infants, while 1-6B and 2-2B were isolated from the same children 5 years later. The sequences permit investigations of factors enabling long-term colonization of bifidobacteria.

12.
Acta Psychol (Amst) ; 143(1): 88-95, 2013 May.
Article in English | MEDLINE | ID: mdl-23542809

ABSTRACT

Temporal order memory, or remembering the order of events, is critical for everyday functioning and is difficult for patients with mild cognitive impairment (MCI). It is currently unclear whether these patients have difficulty acquiring and/or retaining such information and whether deficits in these patients are in excess of "normal" age-related declines. Therefore, the current study examined age and disease-related changes in temporal order memory as well as whether memory load played a role in such changes. Young controls (n=25), older controls (n=34), and MCI patients (n=32) completed an experimental task that required the reconstruction of sequences that were 3, 4, or 5 items in length both immediately after presentation (i.e., immediate recall) and again after a 10-min delay (i.e., delayed recall). During the immediate recall phase, there was an effect of age largely due to reduced performance at the two longest span lengths. Older controls and MCI patients only differed during the five span (controls>MCI). During the delayed recall, however, there were significant effects of both age and MCI regardless of span length. In MCI patients, immediate recall was significantly correlated with measures of executive functioning, whereas delayed recall performance was only related to other memory tests. These findings suggest that MCI patients experience initial temporal order memory deficits at the point when information begins to exceed working memory capacity and become dependent on medial temporal lobe functioning. Longer-term deficits are due to an inability to retain information, consistent with the characteristic medial temporal lobe dysfunction in MCI.


Subject(s)
Aging/physiology , Cognitive Dysfunction/complications , Cognitive Dysfunction/physiopathology , Memory Disorders/etiology , Memory Disorders/physiopathology , Retention, Psychology/physiology , Temporal Lobe/physiopathology , Adult , Aged , Analysis of Variance , Cognitive Dysfunction/diagnosis , Executive Function , Female , Geriatric Assessment , Humans , Learning , Male , Memory, Episodic , Memory, Short-Term , Mental Recall , Middle Aged , Neuropsychological Tests , Young Adult
13.
Proc Biol Sci ; 279(1728): 553-63, 2012 Feb 07.
Article in English | MEDLINE | ID: mdl-21733904

ABSTRACT

A wide variety of rudimentary and apparently non-functional traits have persisted over extended evolutionary time. Recent evidence has shown that some of these traits may be maintained as a result of developmental constraints or neutral energetic cost, but for others their true function was not recognized. The adipose fin is small, fleshy, non-rayed and located between the dorsal and caudal fins on eight orders of basal teleosts and has traditionally been regarded as vestigial without clear function. We describe here the ultrastructure of the adipose fin and for the first time, to our knowledge, present evidence of extensive nervous tissue, as well as an unusual subdermal complex of interconnected astrocyte-like cells equipped with primary cilia. The fin contains neither adipose tissue nor fin rays. Many fusiform actinotrichia, comprising dense striated macrofibrils, support the free edge and connect with collagen cables that link the two sides. These results are consistent with a recent hypothesis that the adipose fin may act as a precaudal flow sensor, where its removal can be detrimental to swimming efficiency in turbulent water. Our findings provide insight to the broader themes of function versus constraints in evolutionary biology and may have significance for fisheries science, as the adipose fin is routinely removed from millions of salmonids each year.


Subject(s)
Animal Fins/innervation , Animal Fins/ultrastructure , Nerve Net/ultrastructure , Trout/anatomy & histology , Animals , Astrocytes/ultrastructure , Dermis/diagnostic imaging , Dermis/innervation , Epidermis/diagnostic imaging , Epidermis/innervation , Microscopy, Electron, Scanning/veterinary , Nova Scotia , Ultrasonography
14.
J Anim Sci ; 88(8): 2684-91, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20348369

ABSTRACT

Four Hereford steers (500 +/- 4.5 kg of BW) cannulated in the proximal duodenum were used to evaluate the effects of vegetable oil source or fish oil quantity on ruminal biohydrogenation (BH) and CLA outflow. Steers were fed 1 of 4 treatment diets in a 2 x 2 factorial arrangement of treatments (oil source: canola vs. corn oil; fish oil quantity: 0 or 1%) in a 4 x 4 Latin square design. The remainder of the diet included chopped bermudagrass hay, dry-rolled corn, and protein/mineral supplement. Duodenal samples were collected for 4 d after 11-d diet adaptation periods. Data were analyzed with animal, period, oil source, fish oil, and 2-way interaction among oil source and fish oil quantity in the model. All interactions among oil source and fish oil inclusion were nonsignificant with the exception of trans-11 vaccenic acid (TVA) and trans-9 octadecenoic acid. Intake and duodenal flow of total long-chain fatty acids did not differ between treatments. Apparent ruminal DM digestibility was not altered by oil source or fish oil inclusion. Apparent ruminal digestion of fatty acids did not differ among oil sources but was increased (P = 0.03) with fish oil supplementation. Ruminal BH of oleic and linolenic acids was increased (P = 0.01) for diets containing supplemental canola oil compared with corn oil. Ruminal BH of linoleic acid was greater (P = 0.01) for diets containing supplemental corn oil compared with canola oil. Fish oil addition reduced (P = 0.01) oleic acid BH but did not alter (P > 0.26) linoleic or linolenic acid BH. Duodenal flow of palmitic acid was greater (P = 0.05) for steers supplemented with corn oil compared with canola oil. Fish oil inclusion in the diet increased (P = 0.01) flow of n-3 fatty acids (eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid), trans-10 octadecenoic acid, trans-12 octadecenoic acid, and cis-9, trans-11 CLA. Trans-9 octadecenoic acid and TVA flows to the duodenum were increased (P = 0.01) when fish oil was included in the canola oil-supplemented diet; however, no changes were observed when fish oil was included in the corn oil-supplemented diet (P of interaction = 0.06 and 0.08). Fish oil inclusion increased the outflow of n-3 fatty acids, trans-10 octadecenoic acid, and the majority of CLA isomers including cis-9, trans-11. These results suggest that fish oil addition alters ruminal formation of BH intermediates that is dependent on oil source supplemented in the diet.


Subject(s)
Cattle/metabolism , Diet/veterinary , Fatty Acids/metabolism , Fish Oils/pharmacology , Linoleic Acid/metabolism , Plant Oils/pharmacology , Rumen/metabolism , Animal Feed , Animals , Corn Oil/pharmacology , Dietary Supplements , Eating/drug effects , Fatty Acids, Monounsaturated/pharmacology , Hydrogenation/drug effects , Male , Rapeseed Oil
15.
J Thromb Haemost ; 7(4): 710-9, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19192108

ABSTRACT

BACKGROUND AND OBJECTIVES: Anti-heat shock protein (HSP)60 autoantibodies are associated with atherosclerosis and are known to affect endothelial cells in vitro. However, their role in thrombus formation remains unclear. We hypothesized that anti-HSP60 autoantibodies could potentiate thrombosis, and evaluated the effect of anti-murine HSP60 antibodies in a ferric chloride (FeCl3)-induced murine model of carotid artery injury. METHODS: Anti-HSP60, or control, IgG was administered to BALB/c mice 48 h prior to inducing carotid artery injury, and blood flow was monitored using an ultrasound probe. RESULTS: Thrombus formation was more rapid and stable in anti-HSP60 IGG-treated mice than in controls (blood flow=1.7%+/-0.6% vs. 34%+/-12.6%, P=0.0157). Occlusion was complete in all anti-HSP60 IgG-treated mice (13/13), with no reperfusion being observed. In contrast, 64% (9/14) of control mice had complete occlusion, with reperfusion occurring in 6/9 mice. Thrombi were significantly larger in anti-HSP60 IgG-treated mice (P=0.0001), and contained four-fold more inflammatory cells (P=0.0281) than in controls. Non-injured contralateral arteries of anti-HSP60 IgG-treated mice were also affected, exhibiting abnormal endothelial cell morphology and significantly greater von Willebrand factor (VWF) and P-selectin expression than control mice (P=0.0024 and P=0.001, respectively). CONCLUSIONS: In summary, the presence of circulating anti-HSP60 autoantibodies resulted in increased P-selectin and VWF expression and altered cell morphology in endothelial cells lining uninjured carotid arteries, and promoted thrombosis and inflammatory cell recruitment in FeCl3-injured carotid arteries. These findings suggest that anti-HSP60 autoantibodies may constitute an important prothrombotic risk factor in cardiovascular disease in human vascular disease.


Subject(s)
Autoantibodies/pharmacology , Chaperonin 60/immunology , Thrombosis/immunology , Animals , Arterial Occlusive Diseases/etiology , Arterial Occlusive Diseases/immunology , Autoantibodies/administration & dosage , Carotid Artery Diseases/etiology , Carotid Artery Diseases/immunology , Chlorides , Disease Models, Animal , Ferric Compounds , Mice , P-Selectin/analysis , Regional Blood Flow , Reperfusion , Thrombosis/etiology , von Willebrand Factor/analysis
16.
Nat Neurosci ; 11(8): 880-1, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18587392

ABSTRACT

Previous emotion regulation research has been successful in altering aversive emotional reactions. It is unclear, however, whether such strategies can also efficiently regulate expectations of reward arising from conditioned stimuli, which can at times be maladaptive (for example, drug cravings). Using a monetary reward-conditioning procedure with cognitive strategies, we observed attenuation in both the physiological (skin conductance) and neural correlates (striatum) of reward expectation as participants engaged in emotion regulation.


Subject(s)
Cognition/physiology , Corpus Striatum/physiology , Emotions/physiology , Inhibition, Psychological , Reward , Conditioning, Classical/physiology , Corpus Striatum/anatomy & histology , Cues , Electric Conductivity , Humans , Magnetic Resonance Imaging , Skin Physiological Phenomena
17.
Proc Natl Acad Sci U S A ; 105(19): 7028-33, 2008 May 13.
Article in English | MEDLINE | ID: mdl-18474859

ABSTRACT

We recently demonstrated early metabolic alterations in the dystrophin-deficient mdx heart that precede overt cardiomyopathy and may represent an early "subclinical" signature of a defective nitric oxide (NO)/cGMP pathway. In this study, we used genetic and pharmacological approaches to test the hypothesis that enhancing cGMP, downstream of NO formation, improves the contractile function, energy metabolism, and sarcolemmal integrity of the mdx heart. We first generated mdx mice overexpressing, in a cardiomyocyte-specific manner, guanylyl cyclase (GC) (mdx/GC(+/0)). When perfused ex vivo in the working mode, 12- and 20-week-old hearts maintained their contractile performance, as opposed to the severe deterioration observed in age-matched mdx hearts, which also displayed two to three times more lactate dehydrogenase release than mdx/GC(+/0). At the metabolic level, mdx/GC(+/0) displayed a pattern of substrate selection for energy production that was similar to that of their mdx counterparts, but levels of citric acid cycle intermediates were significantly higher (36 +/- 8%), suggesting improved mitochondrial function. Finally, the ability of dystrophin-deficient hearts to resist sarcolemmal damage induced in vivo by increasing the cardiac workload acutely with isoproterenol was enhanced by the presence of the transgene and even more so by inhibiting cGMP breakdown using the phosphodiesterase inhibitor sildenafil (44.4 +/- 1.0% reduction in cardiomyocyte damage). Overall, these findings demonstrate that enhancing cGMP signaling, specifically downstream and independent of NO formation, in the dystrophin-deficient heart improves contractile performance, myocardial metabolic status, and sarcolemmal integrity and thus constitutes a potential clinical avenue for the treatment of the dystrophin-related cardiomyopathies.


Subject(s)
Cardiomyopathies/prevention & control , Cyclic GMP/metabolism , Dystrophin/deficiency , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Piperazines/pharmacology , Signal Transduction/drug effects , Sulfones/pharmacology , Animals , Atrial Natriuretic Factor/genetics , Atrial Natriuretic Factor/metabolism , Cardiomyopathies/enzymology , Cardiomyopathies/physiopathology , Enzyme Activation/drug effects , Gene Expression Regulation/drug effects , Guanylate Cyclase/genetics , Guanylate Cyclase/metabolism , Heart Rate/drug effects , In Vitro Techniques , Mice , Mice, Transgenic , Mitochondria/drug effects , Mitochondria/metabolism , Myocardial Contraction/drug effects , Myocytes, Cardiac/enzymology , Myocytes, Cardiac/pathology , Organ Specificity/drug effects , Purines/pharmacology , Sarcolemma/drug effects , Sarcolemma/metabolism , Sildenafil Citrate
18.
Br J Pharmacol ; 154(4): 749-57, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18414390

ABSTRACT

BACKGROUND AND PURPOSE: High resting heart rate is a predictor for total and cardiovascular mortality independent of other risk factors in patients with coronary artery disease. We tested the hypothesis that a reduction of resting heart rate with the cardiac pacemaker I(f) current inhibitor ivabradine prevents the endothelial dysfunction associated with dyslipidaemia. EXPERIMENTAL APPROACH: Three-month-old dyslipidaemic (DL) male mice expressing the human ApoB-100 were assigned or not (DL, n=16), to treatment for 3 months with ivabradine (10 mg kg(-1) d(-1), n=17). Wild-type C57Bl/6 mice (WT, n=15) were used as controls. Heart rate was measured at 3, 4.5 and 6 months. Dilatation to acetylcholine (ACh) of isolated cerebral and renal arteries was investigated at 6 months. KEY RESULTS: Heart rate remained stable in anaesthetized WT mice, increased (25%, P<0.05) with age in DL mice but was limited (11%, P<0.05) by ivabradine. At 6 months, left ventricular maximal pressure was similar in all groups. The minimal and end-diastolic left ventricular pressures were increased (P<0.05) in DL (10.2+/-1.0 and 18.7+/-1.4 mm Hg) compared to WT (-0.4+/-0.7 and 6.3+/-1.0 mm Hg) and reduced (P<0.05) by ivabradine (4.2+/-1.3 and 11.5+/-1.5 mm Hg). ACh-induced maximal dilatation was impaired (P<0.05) in renal and cerebral arteries isolated from DL compared to WT (56+/-7 versus 83+/-3% in renal arteries; 22+/-2 versus 42+/-2% in cerebral arteries). Ivabradine completely prevented (P<0.05) this dysfunction in renal and cerebral arteries. CONCLUSIONS AND IMPLICATIONS: Selective heart rate reduction with ivabradine limits cardiac dysfunction and prevents the renovascular and cerebrovascular endothelial dysfunction associated with dyslipidaemia.


Subject(s)
Benzazepines/pharmacology , Cardiotonic Agents/pharmacology , Endothelium, Vascular/drug effects , Heart Rate/drug effects , Acetylcholine , Animals , Apolipoprotein B-100/genetics , Blood Pressure/drug effects , Cerebral Arteries/drug effects , Cerebral Arteries/metabolism , Dyslipidemias/complications , Endothelium, Vascular/physiopathology , Ivabradine , Male , Mice , Mice, Inbred C57BL , Renal Artery/drug effects , Renal Artery/metabolism , Time Factors , Vasodilation/drug effects
19.
J Anim Sci ; 85(6): 1504-10, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17339415

ABSTRACT

Thirty-six Angus x Hereford heifers were used in a 3 x 2 factorial (3 dietary treatments; 2 supplementation times) to examine the effect of dietary lipid supplementation on lipid oxidation, lipid composition, and palatability of ribeye steaks and ground beef. Lipid was supplied in the diets as corn oil or a partially rumen-protected CLA salt for 2 specific treatment periods of the final 32 or 60 d on feed, corresponding to a total time on feed of 89 or 118 d. After an initial 56-d feeding period (basal diet), the heifers were fed 1 of 3 dietary treatments (DM basis): 1) a basal diet containing 88% concentrate and 12% grass hay (CON), 2) the basal diet plus 4% corn oil (OIL), or 3) the basal diet plus 2% partially rumen-protected CLA (RPCLA) containing 31% CLA. Heifers were randomly allotted to dietary treatments at the initiation of the study and fed individually. At 48 h postmortem, the right forequarter of each carcass was fabricated into retail cuts. Steaks (2.54-cm thick) were obtained from the posterior end of the ribeye roll (NAMP 112), and beef trim was ground for all subsequent analyses. Dietary treatment did not affect (P > 0.05) lipid oxidation in ground beef or ribeye steaks. Total trans-octadecenoate fat and trans-10 octadecenoic acid content in ribeye steaks increased (P < 0.05) with RPCLA compared with CON. Total CLA and the cis-9 trans-11 isomer of CLA contents in ribeye steaks were unchanged (P > 0.05) by lipid supplementation. In ground beef, RPCLA supplementation increased (P < 0.05) the amount of trans fat and trans-10 octadecenoic acid compared with CON or OIL; supplementation of RPCLA increased (P < 0.05) the amount of CLA cis-9 trans-11 isomer and total CLA. Lipid supplementation did not alter (P > 0.05) off-flavor ratings in ground beef or ribeye steaks. Supplementation of corn oil increased (P < 0.05) total PUFA content of ribeye steaks compared with CON and RPCLA. Dietary RPCLA supplementation increased the amount of trans fat per serving (85.5 g, broiled) by 110 and 88% in ribeye steak and ground beef, respectively, and CLA cis-9 trans-11 by 58% in ground beef compared with CON. Supplementing OIL or RPCLA resulted in minimal changes in lipid oxidation and sensory attributes of steaks and ground beef.


Subject(s)
Corn Oil/pharmacology , Dietary Supplements , Linoleic Acids, Conjugated/pharmacology , Meat/standards , Animal Feed , Animal Nutritional Physiological Phenomena , Animals , Body Composition/drug effects , Cattle , Corn Oil/administration & dosage , Corn Oil/metabolism , Diet/veterinary , Fatty Acids/analysis , Female , Linoleic Acids, Conjugated/administration & dosage , Linoleic Acids, Conjugated/metabolism , Meat/analysis
20.
Eur Arch Otorhinolaryngol ; 263(2): 183-7, 2006 Feb.
Article in English | MEDLINE | ID: mdl-15981017

ABSTRACT

Substitution voicing cannot be evaluated accurately by the GRBAS perceptual rating scale, and there is a need for a valuable alternative. Therefore, we developed and tried out a perceptual rating scale, consisting of five new parameters: impression, intelligibility, noise, fluency and voicing, each to be scored between 0 (very bad score) to 10 (very good score for a substitution voice). In analogy to the GRBAS scale, they are then converted to deviance scores ranging from 0 (similar to good substitution voicing) to 3 (very deviant from good substitution voicing). Inter-individual agreement measured in a set of 24 semi-professional jury members seemed to be moderate for all parameters. Mean figures of 0.52, 0.51, 0.46, 0.53 and 0.46 are obtained for the parameters impression, intelligibility, noise, fluency and voicing, respectively. Because a high correlation exists between the first two parameters (0.917) and relying on the correlation figures between the two "I"s and the other parameters (correlation values for "impression" vary from 0.79-0.86; values for "intelligibility" range from 0.74-0.83), we suggest to discard the parameter impression, which turns the actual IINFVo scale into INFVo. The proposed (I)INFVo perceptual rating scale seems promising for the assessment of substitution voicing. Eventual improvements and practical proposals are discussed.


Subject(s)
Speech Perception , Voice Disorders/diagnosis , Voice Disorders/epidemiology , Voice Quality , Humans , Observer Variation , Severity of Illness Index , Surveys and Questionnaires
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