Heart Rate Variability as an Index of Resilience.

INTRODUCTION: Resilience is the ability to maintain or quickly return to a stable physical and psychological equilibrium despite experiencing stressful events. Flexibility of the autonomic nervous system is particularly important for adaptive stress responses and may contribute to individual differences in resilience. Power spectrum analysis of heart rate variability (HRV) allows measurement of sympathovagal balance, which helps to evaluate autonomic flexibility. The present study investigated HRV as a broad index of resilience. MATERIALS AND METHODS: Twenty-four male participants from the Army National Guard Special Forces completed psychological measures known to relate to resilience and had HRV measured while undergoing stressful virtual environment scenarios. Pearson product-moment correlations were used to explore the relationships between HRV and resilience factors. All research was conducted with the oversight of the Human Subjects Review Committee of Fuller Theological Seminary. RESULTS: Trends toward significance were reported in order to provide results that would reasonably be expected in a study of higher power. Trends between resilience factors and HRV were found only during specific stress-inducing simulations (see Tables III). CONCLUSION: Greater resilience to stress was associated with HRV during nonstress periods. Higher levels of resilience to traumatic events were associated with HRV during circumstances that were more stressful and emotionally distressing. Post hoc analysis revealed that specific factors including flexibility, emotional control, and spirituality were driving the relationship between general resilience and HRV following emotionally laden stressors. Less stress vulnerability was associated with HRV following intermittent brief stressors. In sum, HRV appears to represent some aspects of an individual's overall resilience profile. Although resilience remains a complex, multidimensional construct, HRV shows promise as a global psychophysiological index of resilience. This study also offers important perspectives concerning ways to optimize both physical and psychological health.

Enhanced phagocytic capacity endows chondrogenic progenitor cells with a novel scavenger function within injured cartilage.

OBJECTIVE: Articular cartilage harbors chondrogenic progenitor cells (CPCs), a population that responds chemotactically to cell death. Because this behavior is reminiscent of macrophages, we hypothesized that CPCs have macrophage-like capabilities for scavenging cell and tissue debris through phagocytosis. DESIGN: CPCs, chondrocytes, synoviocytes, and macrophages were cultured with fluorophore-labeled chondrocyte debris for 3, 6, 12, or 24 h. Debris internalization was quantified by confocal microscopy and flow cytometry. Confocal microscopy was also used to test CPCs and chondrocytes for uptake of fluorophore-labeled fibronectin fragments (Fn-fs), a form of extracellular matrix debris. Lysosome activity and mass in CPCs and chondrocytes were measured using fluorescent probes. The relative expression of phagocytosis-related genes and proteins was evaluated by polymerase chain reaction (PCR) and immunoblotting, respectively. Pulse-chase experiments were performed to determine if the debris internalized by CPCs and chondrocytes was cleared, and if clearance was affected by a cathepsin B inhibitor. RESULTS: More macrophages, synoviocytes, and CPCs internalized cell debris than chondrocytes at all time points. While uptake remained flat in chondrocytes at ∼10%, in the other cell types it peaked at more than 60% after 12-24 h. Relative to chondrocytes, CPCs showed significantly higher rates of Fn-fs engulfment, greater lysosome activity and mass, and over-expressed phagocytosis-related genes and proteins. Pulse-chase experiments revealed time- and cathepsin B-dependent clearance of cell debris in CPCs, but not in chondrocytes. CONCLUSIONS: CPCs phagocytized cell and matrix debris much more efficiently than chondrocytes, supporting the hypothesis that they play a macrophage-like role in injured cartilage.

Allostatic Load as a Complex Clinical Construct: A Case-Based Computational Modeling Approach.

Allostatic load (AL) is a complex clinical construct, providing a unique window into the cumulative impact of stress. However, due to its inherent complexity, AL presents two major measurement challenges to conventional statistical modeling (the field's dominant methodology): it is comprised of a complex causal network of bioallostatic systems, represented by an even larger set of dynamic biomarkers; and, it is situated within a web of antecedent socioecological systems, linking AL to differences in health outcomes and disparities. To address these challenges, we employed case-based computational modeling (CBM), which allowed us to make four advances: (1) we developed a multisystem, 7-factor (20 biomarker) model of AL's network of allostatic systems; (2) used it to create a catalog of nine different clinical AL profiles (causal pathways); (3) linked each clinical profile to a typology of 23 health outcomes; and (4) explored our results (post hoc) as a function of gender, a key socioecological factor. In terms of highlights, (a) the Healthy clinical profile had few health risks; (b) the pro-inflammatory profile linked to high blood pressure and diabetes; (c) Low Stress Hormones linked to heart disease, TIA/Stroke, diabetes, and circulation problems; and (d) high stress hormones linked to heart disease and high blood pressure. Post hoc analyses also found that males were overrepresented on the High Blood Pressure (61.2%), Metabolic Syndrome (63.2%), High Stress Hormones (66.4%), and High Blood Sugar (57.1%); while females were overrepresented on the Healthy (81.9%), Low Stress Hormones (66.3%), and Low Stress Antagonists (stress buffers) (95.4%) profiles.

Clinical outcomes of patellar chondral lesions treated with juvenile particulated cartilage allografts.

BACKGROUND: Juvenile particulated cartilage allograft (DeNovo NT®, Zimmer, Warsaw, IN) transplantation is a relatively new technology for the treatment of high-grade cartilage lesions. To date there is limited literature demonstrating its effectiveness and safety. The present study specifically looks at the short-term efficacy of DeNovo NT® allograft for symptomatic high-grade cartilage lesions of the patella. Clinical outcomes and complications are reported. METHODS: Seventeen cases of DeNovo NT® allograft transplantation at our institution were retrospectively reviewed from 2010 to 2013. Thirteen patients had the procedure performed for patellar lesions and are included in the present study. A chart review was performed to record demographic data, surgical technique, and complications. In addition, we analyzed preoperative and postoperative KOOS outcome scores. RESULTS: The mean age was 22.5 years (range, 14-34), with 3 males and 10 females. Mean follow-up was 8.2 months (range, 0.67-32.7). Six of the patients had concomitant anteromedialization of the tibial tubercle. DeNovo NT® allograft transplantation resulted in improvement for each outcome measure used. Overall KOOS score significantly improved from a mean of 58.4±15.7 to 69.2±18.6 (P = 0.04). Improvement in KOOS subscales of pain, ADL, and symptoms all approached but did not reach statistical significance (P values between 0.05 and 0.10). There were no infections or hardware complications. CONCLUSIONS: This series demonstrates that DeNovo NT® allograft transplantation for symptomatic high-grade cartilage lesions of the patella results in pain relief and improved outcomes in the short term. Further studies are needed to better evaluate this new technology. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Single cell sorting identifies progenitor cell population from full thickness bovine articular cartilage.

OBJECTIVE: To date, no approved clinical intervention successfully prevents the progressive degradation of injured articular cartilage that leads to osteoarthritis (OA). Stem/progenitor cell populations within tissues of diarthrodial joint have shown their therapeutic potential in treating OA. However, this potential has not been fully realized due in part to the heterogeneity of these subpopulations. Characterization of clonal populations derived from a single cell may help identify more homogenous stem/progenitor populations within articular cartilage. Moreover, chondrogenic potential of clonal populations from different zones could be further examined to elucidate their differential roles in maintaining articular cartilage homeostasis. METHOD: We combined Fluorescence-activated cell sorting (FACS) and clonogenicity screening to identify stem/progenitor cells cloned from single cells. High-efficiency colony-forming cells (HCCs) were isolated, and evaluated for stem/progenitor cell characteristics. HCCs were also isolated from different zones of articular cartilage. Their function was compared by lineage-specific gene expression, and differentiation potential. RESULTS: A difference in colony-forming efficiency was observed in terms of colony sizes. HCCs were highly clonogenic and multipotent, and overexpressed stem/progenitor cell markers. Also, proliferation and migration associated genes were over-expressed in HCCs. HCCs showed zonal differences with deep HCCs more chondrogenic and osteogenic than superficial HCCs. CONCLUSION: Our approach is a simple yet practical way to identify homogeneous stem/progenitor cell populations with clonal origin. The discovery of progenitor cells demonstrates the intrinsic self-repairing potential of articular cartilage. Differences in differentiation potential may represent the distinct roles of superficial and deep zone stem/progenitor cells in the maintenance of articular cartilage homeostasis.

A low-power, high-speed, 9-channel germanium-silicon electro-absorption modulator array integrated with digital CMOS driver and wavelength multiplexer.

We demonstrate the first germanium-silicon C-band electro-absorption based waveguide modulator array and echelle-grating-based silicon wavelength multiplexer integrated with a digital CMOS driver circuit. A 9-channel, 10Gbps SiGe electro-absorption wavelength-multiplexed modulator array consumed a power of 5.8mW per channel while being modulated at 10.25Gbps by 40nm CMOS drivers delivering peak-to-peak voltage swings of 2V, achieving a modulation energy-efficiency of ~570fJ/bit including drivers. Performance up to 25Gbps on a single-channel SiGe modulator and CMOS driver is also reported.

Self-Reported Differences in Personality, Emotion Control, and Presence Between Pre-Military and Non-Military Groups in a Pilot Study Using the Stress Resilience in Virtual Environments (STRIVE) System.

Mental health disorders are the signature wounds of war resulting from extended U.S. Military conflicts in the Middle East [1]. In an effort to abate the number of Service Members that develop mental health disorders in these conflicts, USC-ICT has created the Stress Resilience in Virtual Environments (STRIVE) project, a set of highly realistic virtual reality combat scenarios and resilience-building sessions designed for pre-deployed military personnel. This short-paper looks at self-reported differences in personality, emotion control, and presence between two different groups, pre-military and non-military, of pilot subjects that tested a prototype of the first four modules of STRIVE.

Expansion of a VR Exposure Therapy System for Combat-Related PTSD to Medics/Corpsman and Persons Following Military Sexual Trauma.

The stressful experiences that have been characteristic of the combat environments in Iraq and Afghanistan have produced significant numbers of returning service members at risk for developing posttraumatic stress disorder and other psychosocial/behavioral health conditions. This paper describes a set of projects that are expanding the content for inclusion in a newly updated "Virtual Iraq/Afghanistan" Virtual Reality system for the delivery of exposure therapy (VRET) for PTSD with Service Members and Veterans. In addition to the complete rebuilding of this VRET system using the latest version of the Unity Game Engine, the system's content and functionality has been expanded to now support the use of VRET with combat medics/corpsmen and persons who have experienced military sexual trauma (MST). The focus of this paper is to present the rationale and general overview of the progress on these projects that will provide new relevant and customizable options for conducting VRET with a wider range of trauma experiences.

STRIVE: Stress Resilience In Virtual Environments: a pre-deployment VR system for training emotional coping skills and assessing chronic and acute stress responses.

The incidence of posttraumatic stress disorder (PTSD) in returning OEF/OIF military personnel is creating a significant healthcare challenge. This has served to motivate research on how to better develop and disseminate evidence-based treatments for PTSD. One emerging form of treatment for combat-related PTSD that has shown promise involves the delivery of exposure therapy using immersive Virtual Reality (VR). Initial outcomes from open clinical trials have been positive and fully randomized controlled trials are currently in progress to further validate this approach. Based on our research group's initial positive outcomes using VR to emotionally engage and successfully treat persons undergoing exposure therapy for PTSD, we have begun development in a similar VR-based approach to deliver stress resilience training with military service members prior to their initial deployment. The Stress Resilience In Virtual Environments (STRIVE) project aims to create a set of combat simulations (derived from our existing Virtual Iraq/Afghanistan exposure therapy system) that are part of a multi-episode narrative experience. Users can be immersed within challenging combat contexts and interact with virtual characters within these episodes as part of an experiential learning approach for training a range of psychoeducational and cognitive-behavioral emotional coping strategies believed to enhance stress resilience. The STRIVE project aims to present this approach to service members prior to deployment as part of a program designed to better prepare military personnel for the types of emotional challenges that are inherent in the combat environment. During these virtual training experiences users are monitored physiologically as part of a larger investigation into the biomarkers of the stress response. One such construct, Allostatic Load, is being directly investigated via physiological and neuro-hormonal analysis from specimen collections taken immediately before and after engagement in the STRIVE virtual experience.

Mitochondrial electron transport and glycolysis are coupled in articular cartilage.

OBJECTIVE: Although the majority of the adenosine triphosphate (ATP) in chondrocytes is made by glycolysis rather than by oxidative phosphorylation in mitochondria there is evidence to suggest that reactive oxygen species produced by mitochondrial electron transport (ET) help to maintain cellular redox balance in favor of glycolysis. The objective of this study was to test this hypothesis by determining if rotenone, which inhibits ET and blocks oxidant production inhibits glycolytic ATP synthesis. DESIGN: Bovine osteochondral explants were treated with rotenone, an ET inhibitor; or oligomycin an ATP synthase inhibitor; or 2-fluoro-2-deoxy-D-glucose, a glycolysis inhibiter; or peroxide, an exogenous oxidant; or mitoquinone (MitoQ), a mitochondria-targeted anti-oxidant. Cartilage extracts were assayed for ATP, nicotine adenine dinucleotide (NAD+/H), and culture medium was assayed for pyruvate and lactate after 24 h of treatment. Imaging studies were used to measure superoxide production in cartilage. RESULTS: Rotenone and 2-FG caused a significant decline in cartilage ATP (P < 0.001). In contrast, ATP levels were not affected by oligomycin. Peroxide treatment blocked rotenone effects on ATP, while treatment with MitoQ significantly suppressed ATP levels. Rotenone and 2-FG caused a significant decline in pyruvate, but not in lactate production. NADH:NAD+ ratios decreased significantly in both rotenone and 2-FG-treated explants (P < 0.05). Rotenone also significantly reduced superoxide production. CONCLUSIONS: These findings showing a link between glycolysis and ET are consistent with previous reports on the critical need for oxidants to support normal chondrocyte metabolism. They suggest a novel role for mitochondria in cartilage homeostasis that is independent of oxidative phosphorylation.

The effect of aging on adrenergic and nonadrenergic receptor expression and responsiveness in canine skeletal muscle.

We tested the hypothesis that adrenergic and nonadrenergic receptor responsiveness and protein expression would be altered with advancing age. Young (n = 6; 22 ± 1 mo; mean ± SE) and old (n = 6; 118 ± 9 mo) beagles were instrumented with flow probes and an indwelling catheter for continuous measurement of external iliac blood flow and arterial blood pressure. Vascular conductance (VC) was calculated as hindlimb blood flow/mean arterial pressure. Selective agonists for α-1, α-2, neuropeptide-Y (NPY), and purinergic (P2X) receptors were infused at rest and during treadmill running at moderate (2.5 mph) and heavy (4 mph with 2.5% grade) exercise intensities. Feed arteries were dissected from gracilis muscles, and α-1D, α-1B, α-2A, P2X-4, P2X-1, and NPY-Y1 receptor protein expression was determined. Phenylephrine produced similar decreases (P > 0.05) in VC in young and old beagles at rest (young: -62 ± 5%; old: -59 ± 5%) and during moderate (young: -67 ± 5%; old: -62 ± 4%) and heavy (young: -54 ± 4%; old: -49 ± 3%) exercise. Clonidine caused similar (P > 0.05) decreases in VC in old compared with young dogs at rest (young: -59 ± 8%; old: -70 ± 6%) and during moderate (young: -52 ± 6%; old: -47 ± 5%)- and heavy (young: -42 ± 5%; old: -43 ± 5%)-intensity exercise. NPY infusion resulted in a similar decline in VC in young and old beagles at rest (young: -40 ± 7%; old: -39 ± 9%) and during moderate (young: -47 ± 6%; old: -40 ± 6%)- and heavy (young: -40 ± 3%; old: -38 ± 4%)-intensity exercise. α-ß-Methylene-ATP also produced similar decreases in VC in young and old beagles at rest (young: -36 ± 6%; old: -40 ± 8%) and during exercise at moderate (young: -42 ± 5%; old: -40 ± 9%) and heavy (young: -47 ± 5%; old: -42 ± 8%) intensities. α-1B receptor protein expression was elevated (P < 0.05) in old compared with young dogs, whereas there were no age-related differences in α-1D or α-2A receptor expression and nonadrenergic P2X-4, P2X-1, and NPY-Y1 receptor expression. The present findings indicate that postsynaptic adrenergic and nonadrenergic receptor responsiveness was not altered by advancing age. Moreover, the expression of adrenergic and nonadrenergic receptors in skeletal-muscle feed arteries was largely unaffected by aging.

Biomechanical disc culture system: feasibility study using rat intervertebral discs.

A small-scale biomechanical disc culture system was designed to stimulate intervertebral disc (IVD) 'motion segment' in culture environment with load-controlled compression and combined load (compression+shear). After 7 days of diurnal mechanical loading, cell viability of discs stimulated with static compression load (0.25 MPa) and static combined load (compression (0.25 MPa)+shear (1.5N)) were similar (>90 per cent) to unloaded controls. Mechanically stimulated discs showed decrease in static/dynamic moduli, early stress relaxation, and loss of disc height after 7 days of diurnal loading. Histological data of discs indicated load-induced transformations that were not apparent in controls. The feasibility of studying the mechanobiology of intact IVD as a motion segment was demonstrated. Media conditioning (improve tissue stability in long-term culture) and application of biochemical gene expression assays (differential tissue response to types of mechanical stimulation) are proposed as future improvements. The study suggests that the limitations in studying mechanobiology of IVD pathology in vitro can be overcome and it is possible to understand the physiologically relevant mechanism of IVD pathology.

Recommendations of the OARSI FDA Osteoarthritis Devices Working Group.

Osteoarthritis (OA) is the most common type of arthritis and a major cause of chronic musculoskeletal pain and functional disability. While both pharmacologic and non-pharmacologic modalities are recommended in the management of OA, when patients with hip or knee OA do not obtain adequate pain relief and/or functional improvement, joint replacement surgery or other surgical interventions should be considered. Total joint arthroplasties are reliable and cost-effective treatments for patients with significant OA of the hip and knee. Evidence from cohort and observational studies has confirmed substantial improvements in pain relief with cumulative revision rates at 10 years following total hip (THA) and total knee arthroplasties (TKA) at 7% and 10%, respectively. Joint replacements have been used in most every synovial joint, although results for joints other than hip and knee replacement have not been as successful. The evolution of new device designs and surgical techniques highlights the need to better understand the risk to benefit ratio for different joint replacements and to identify the appropriate methodology for evaluating the efficacy and optimal outcomes of these new devices, designed to treat OA joints.

Mechanical impact induces cartilage degradation via mitogen activated protein kinases.

OBJECTIVE: To determine the activation of Mitogen activated protein (MAP) kinases in and around cartilage subjected to mechanical damage and to determine the effects of their inhibitors on impaction-induced chondrocyte death and cartilage degeneration. DESIGN: The phosphorylation of MAP kinases was examined with confocal microscopy and immunoblotting. The effects of MAP kinase inhibitors on impaction-induced chondrocyte death and proteoglycan (PG) loss were determined with fluorescent microscopy and 1, 9-Dimethyl-Methylene Blue (DMMB) assay. The expression of catabolic genes at mRNA levels was examined with quantitative real-time PCR. RESULTS: Early p38 activation was detected at 20 min and 1h post-impaction. At 24h, enhanced phosphorylation of p38 and extracellular signal-regulated protein kinase (ERK)1/2 was visualized in chondrocytes from in and around impact sites. The phosphorylation of p38 was increased by 3.0-fold in impact sites and 3.3-fold in adjacent cartilage. The phosphorylation of ERK-1 was increased by 5.8-fold in impact zone and 5.4-fold in adjacent cartilage; the phosphorylation of ERK-2 increased by 4.0-fold in impacted zone and 3.6-fold in adjacent cartilage. Furthermore, the blocking of p38 pathway did not inhibit impaction-induced ERK activation. The inhibition of p38 or ERK pathway significantly reduced injury-related chondrocyte death and PG losses. Quantitative Real-time PCR analysis revealed that blunt impaction significantly up-regulated matrix metalloproteinase (MMP)-13, Tumor necrosis factor (TNF)-α, and ADAMTS-5 expression. CONCLUSION: These findings implicate p38 and ERK mitogen activated protein kinases (MAPKs) in the post-injury spread of cartilage degeneration and suggest that the risk of post-traumatic osteoarthritis (PTOA) following joint trauma could be decreased by blocking their activities, which might be involved in up-regulating expressions of MMP-13, ADAMTS-5, and TNF-α.

Is tonic sympathetic vasoconstriction increased in the skeletal muscle vasculature of aged canines?

We tested the hypothesis that tonic adrenergic and nonadrenergic receptor-mediated sympathetic vasoconstriction would increase at rest and during exercise with advancing age. Young (n = 6; 22 ± 1 mo; means ± SE) and old (n = 6; 118 ± 9 mo) beagles were studied. Selective antagonists for alpha-1, alpha-2, neuropeptide Y (NPY), and purinergic (P(2x)) receptors were infused at rest and during treadmill running at 2.5 mph and 4 mph with 2.5% grade. Prazosin produced similar increases in vascular conductance in young and old beagles at rest (Young: 158 ± 34%; Old: 98 ± 19%) and during exercise at 2.5 mph (Young: 80 ± 10%; Old: 58 ± 12%) and 4 mph and 2.5% grade (Young: 57 ± 5%; Old: 26 ± 4%). Rauwolscine caused similar (P > 0.05) increases in vascular conductance in old compared with young dogs at rest (Young: 119 ± 25%; Old: 64 ± 22%) and at 2.5 mph (Young: 86 ± 13%; Old: 60 ± 7%) and 4 mph with 2.5% grade (Young: 61 ± 5%; Old: 43 ± 7%). N2-(diphenylacetyl)-N-[4-hydroxyphenyl)methyl]-d-arginine amide (BIBP) caused a smaller increase (P < 0.05) in vascular conductance in old compared with young dogs at rest (Young: 179 ± 44%; Old: 91 ± 22%), whereas similar increases (P > 0.05) of experimental limb vascular conductance in young and old dogs occurred following BIBP during exercise at 2.5 mph (Young: 56 ± 16%; Old: 50 ± 12%) and 4 mph and 2.5% grade (Young: 45 ± 10%; Old: 25 ± 7%). Pyridoxal-phosphate-6-azophenyl-2'-4'-disulfonic acid infusion produced a larger increase in vascular conductance in old compared with young beagles at rest (Young: 88 ± 14%; Old: 191 ± 58%), whereas similar increases were observed at 2.5 mph (Young: 47 ± 18%; Old: 31 ± 11%) and 4 mph with 2.5% grade (Young: 26 ± 13%; Old: -18 ± 8%). At rest, NPY receptor-mediated restraint of skeletal muscle blood flow was reduced with advancing age, whereas P(2x) receptor-mediated restraint of skeletal muscle blood flow was increased. During exercise, the magnitude of adrenergic and nonadrenergic sympathetic vasoconstriction was not different between young and old dogs. Overall, these data demonstrate that adrenergic receptor-mediated vasoconstriction was not elevated at rest, but nonadrenergic sympathetic vasoconstriction was altered under basal conditions in aged beagles.

Relation of synovitis to knee pain using contrast-enhanced MRIs.

BACKGROUND: It has been suggested that synovitis causes joint pain. On non-contrast-enhanced MRIs synovial thickening cannot be assessed and on these images synovitis has been inconsistently associated with pain. OBJECTIVE: To assess synovial thickening in relation to knee pain severity among subjects in the Multicenter Osteoarthritis Study (MOST) using contrast-enhanced (CE) MRI. METHODS: MOST is a cohort study of people who have, or are at high risk of, knee osteoarthritis (OA). An unselected subset of 535 participants who volunteered underwent CE 1.5 T MRI of one knee. Synovitis was scored in six compartments and a summary score was created. Knee pain severity was assessed using the maximum item score on the Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain scale. The association between synovitis and pain severity was examined using a logistic regression model adjusting for age, sex, body mass index (BMI), MRI bone marrow lesions and effusions in the whole sample and in a subgroup without radiographic OA. RESULTS: 454 of the 535 subjects undergoing CE MRI had complete data on synovitis and WOMAC pain. Mean age was 59 years, mean BMI 30 and 48% were women. In knees with moderate pain, 80% had synovitis. For knee pain, synovitis conferred a 9.2-fold increased odds compared with those without synovitis. In knees without radiographic OA (n=329), there was also an association of synovitis with an increased prevalence of pain. CONCLUSION: Synovitis has a strong relation with knee pain severity, an association detected more clearly with CE MRI than suggested by previous studies using non-CE MRI measures of synovitis.

Absence of flow-mediated vasodilation in the rabbit femoral artery.

The purpose of this study was to determine if there is flow-mediated vasodilation of the femoral artery in response to progressive increases in flow within a physiological range observed in the in vivo experiments. Femoral artery blood flow was determined in conscious rabbits (n = 5) using chronically implanted flowprobes. Resting blood flow was 8.3 +/- 0.6 ml/min and increased to 39.9 +/- 5.4 ml/min during high intensity exercise. Femoral arteries (n = 12, 1705 +/- 43 microm outer diameter) harvested from a separate group of rabbits were mounted on cannulas and diameter was continuously monitored by video system. Functional integrity of the endothelium was tested with acetylcholine. The arteries were set at a transmural pressure of 100 mm Hg and preconstricted with phenylephrine to 73 +/- 3% of initial diameter. Using a roller pump with pressure held constant, the arteries were perfused intraluminally with warmed, oxygenated Krebs' solution (pH = 7.4) over a physiological range of flows up to 35 ml/min. As flow increased from 5 ml/min to 35 ml/min, diameter decreased significantly (p < 0.05) from 1285 +/- 58 microm to 1100 +/- 49 microm. Thus, in vessels with a functional endothelium, increasing intraluminal flow over a physiological range of flows produced constriction, not dilation. Based on these results, it seems unlikely that flow-mediated vasodilation in the rabbit femoral artery contributes to exercise hyperemia.

Regional atrophy of the corpus callosum in dementia.

The regional distribution of degeneration of the corpus callosum (CC) in dementia is not yet clear. This study compared regional CC size in participants (n = 179) from the Cache County Memory and Aging Study. Participants represented a range of cognitive function: Alzheimer's disease (AD), vascular dementia (VaD), mild ambiguous (MA-cognitive problems, but not severe enough for diagnosis of dementia), and healthy older adults. CC outlines obtained from midsagittal magnetic resonance images were divided into 99 equally spaced widths. Factor analysis of these callosal widths identified 10 callosal regions. Multivariate analysis of variance revealed significant group differences for anterior and posterior callosal regions. Post-hoc pairwise comparisons of CC regions in patient groups as compared to the control group (controlling for age) revealed trends toward smaller anterior and posterior regions, but not all were statistically significant. As compared to controls, significantly smaller anterior and posterior CC regions were found in the AD group; significantly smaller anterior CC regions in the VaD group; but no significant CC regional differences in the MA group. Findings suggest that dementia-related CC atrophy occurs primarily in the anterior and posterior portions.

Incidence of dementia in long-term hormone users.

Results from epidemiologic studies of postmenopausal hormone use and dementia have been conflicting. Investigators from the Women's Health Initiative Memory Study reported that the incidence of dementia in women aged >/=65 years assigned to hormone use was increased. Here the authors report results from a prospective cohort study of 2,906 dementia-free women (1,519 hormone users and 1,387 hormone nonusers) aged > or =75 years who were recruited from a Southern California health plan in 1999 and followed through 2003. Cognitive status was assessed annually using the Telephone Interview of Cognitive Status-modified, supplemented by the Telephone Dementia Questionnaire and medical record review. The mean self-reported age at initiation of hormone use was 48.3 years for users of estrogen alone (n = 1,072) and 54.9 years for users of estrogen plus progestin (n = 447); self-reported mean durations of hormone use were 30.5 years and 23.2 years, respectively. There were 283 incident dementia cases identified during follow-up. After adjustment for age, education, and medical history, hazard ratios for incident dementia were 1.34 (95% confidence interval: 0.95, 1.89) in estrogen/progestin users and 1.23 (95% confidence interval: 0.94, 1.59) in estrogen users. These findings do not provide support for an effect of estrogen or estrogen/progestin use in preventing dementia.

Evidence for direct projections from the basal nucleus of the amygdala to retrosplenial cortex in the Macaque monkey.

The role of the primate retrosplenial cortex (RSC) in memory processing and spatial navigation has been well established. Recently, processing emotionally salient information has been attributed to the RSC as well. Little anatomical data, however, exist linking the RSC with known emotional processing centers within the brain. The amygdala has been implicated as a substrate for modulating memory for emotionally salient events; yet no study to date has demonstrated that this area has a direct connection in the primate brain. With modern retrograde tracer injections into the RSC and adjacent cortical areas of the monkey (Macaca fascicularis), we demonstrate that there are efferent projections from the basal nucleus of the amygdala to the RSC and area 31. These projections offer anatomical data supporting the hypothesis that the RSC might receive emotionally salient input directly from the amygdala and suggest a role for the RSC as a node within a neural system potentially capable of integrating emotional information for use in memory or other cognitive processes.