Reduced neuronal efficacy in progressive mild cognitive impairment: a prospective fMRI study on visuospatial processing

Mild cognitive impairment (MCI) often refers to the preclinical stage of dementia, where the majority develop Alzheimer's disease (AD). Given that neurodegenerative burden and compensatory mechanisms might exist before accepted clinical symptoms of AD are noticeable, the current prospective study aimed to investigate the functioning of brain regions in the visuospatial networks responsible for preclinical symptoms in AD using event-related functional magnetic resonance imaging (fMRI). Eighteen MCI patients were evaluated and clinically followed for approximately 3 years. Five progressed to AD (PMCI) and eight remained stable (SMCI). Thirteen age-, gender- and education-matched controls also participated. An angle discrimination task with varying task demands was used. Brain activation patterns as well as task demand-dependent and -independent signal changes between the groups were investigated by using an extended general linear model including individual performance (reaction time [RT]) of each single trial. Similar behavioral (RT and accuracy) responses were observed between MCI patients and controls. A network of bilateral activations, e.g. dorsal pathway, which increased linearly with increasing task demand, was engaged in all subjects. Compared with SMCI patients and controls, PMCI patients showed a stronger relation between task demand and brain activity in left superior parietal lobules (SPL) as well as a general task demand-independent increased activation in left precuneus. Altered brain function can be detected at a group level in individuals that progress to AD before changes occur at the behavioral level. Increased parietal activation in PMCI could reflect a reduced neuronal efficacy due to accumulating AD pathology and might predict future clinical decline in patients with MCI.

Reduced hippocampal anisotropy related to anteriorization of alpha EEG in schizophrenia

Dysfunctions of the hippocampus have been suggested to be related to schizophrenia, and reduced connectivity with other brain regions may be a key for the pathophysiology. The aim of this study was to investigate the effect of white matter anomalies in the hippocampus, as a sign of altered connectivity, on the brain electrical activity. We investigated seven first episode schizophrenic patients and seven age, gender and education-matched controls with diffusion tensor imaging and resting EEG. Fractional anisotropy was computed based on diffusion tensor imaging data for the right and left hippocampus for both groups. No group differences were found in hippocampal fractional anisotropy, EEG spectral power and topography. However a significant correlation was found between more anterior alpha activity and lower fractional anisotropy of both hippocampi in schizophrenics, but not in controls. More anterior alpha activity has been described in schizophrenia. We conclude that this feature might depict a group of schizophrenic patients with reduced hippocampal connectivity.

Vascular dysfunction and reduced circulating endothelial progenitor cells in young healthy UK South Asian men

OBJECTIVES: The objective of this study was to examine determinants of excess coronary artery disease risk in UK South Asians, more prevalent in this population than UK Caucasians, by examining differences in risk factors, vascular function, and endothelial progenitor cells (EPCs). METHODS AND RESULTS: 24 South Asian and 25 Caucasian healthy age-matched nonsmoking men were studied. Vascular function was assessed by flow-mediated and GTN brachial artery dilatation and blood flow responses to infusion of ACh, SNP, and L-NMMA. EPC number and function were measured by flow cytometry (CD34, CD133, and KDR positive cells), and CFU/migration assays. Traditional risk factors and anthropometric measurements were similar in the groups. South Asians had higher fasting insulin levels (6.01 versus 3.62 microU/mL; P = 0.02). South Asians had lower FMD (6.9 versus 8.5%; P = 0.003), L-NMMA response (0.8 versus 1.3 mL/min/100 mL; P = 0.03), mean SNP response (9.5+/-0.6 versus 11.6+/-0.6; P = 0.02), EPC number (0.046+/-0.005% versus 0.085+/-0.009%; P = < 0.001), and CFU ability (CFU 4.29+/-1.57 versus 18.86+/-4.00; P = 0.005). EPC number was the strongest predictor of FMD. Ethnicity was the strongest predictor of EPC number. CONCLUSIONS: Healthy South Asian men are more insulin resistant, and demonstrate endothelial dysfunction and reduced EPC number and function compared with Caucasians. These abnormalities may contribute to their increased CAD risk.

Characterizations of partially reduced polyoxometalate catalysts using ammonia adsorption microcalorimetry and methanol oxidation studies / by Suresh Babu Bommineni.

Phosphomolybdic acid (H3PMo12O40) along with niobium,pyridine and niobium exchanged phosphomolybdic acid catalysts were prepared. Ammonia adsorption microcalorimetry and methanol oxidation studies were carried out to investigate the acid sites strength acid/base/redox properties of each catalyst. The addition of niobium, pyridine or both increased the ammonia heat of adsorption and the total uptake. The catalyst with both niobium and pyridine demonstrated the largest number of strong sites. For the parent H3PMo12O40 catalyst, methanol oxidation favors the redox product. Incorporation of niobium results in similar selectivity to redox products but also results in no catalyst deactivation. Incorporation of pyridine instead changes to the selectivity to favor the acidic product. Finally, the inclusion of both niobium and pyridine results in strong selectivity to the acidic product while also showing no catalyst deactivation. Thus the presence of pyridine appears to enhance the acid property of the catalyst while niobium appears to stabilize the active site.

Energy harvesting from body motion using rotational micro-generation

Autonomous system applications are typically limited by the power supply operational lifetime when battery replacement is difficult or costly. A trade-off between battery size and battery life is usually calculated to determine the device capability and lifespan. As a result, energy harvesting research has gained importance as society searches for alternative energy sources for power generation. For instance, energy harvesting has been a proven alternative for powering solar-based calculators and self-winding wristwatches. Thus, the use of energy harvesting technology can make it possible to assist or replace batteries for portable, wearable, or surgically-implantable autonomous systems. Applications such as cardiac pacemakers or electrical stimulation applications can benefit from this approach since the number of surgeries for battery replacement can be reduced or eliminated. Research on energy scavenging from body motion has been investigated to evaluate the feasibility of powering wearable or implantable systems. Energy from walking has been previously extracted using generators placed on shoes, backpacks, and knee braces while producing power levels ranging from milliwatts to watts. The research presented in this paper examines the available power from walking and running at several body locations. The ankle, knee, hip, chest, wrist, elbow, upper arm, side of the head, and back of the head were the chosen target localizations. Joints were preferred since they experience the most drastic acceleration changes. For this, a motor-driven treadmill test was performed on 11 healthy individuals at several walking (1-4 mph) and running (2-5 mph) speeds. The treadmill test provided the acceleration magnitudes from the listed body locations. Power can be estimated from the treadmill evaluation since it is proportional to the acceleration and frequency of occurrence. Available power output from walking was determined to be greater than 1mW/cm³ for most body locations while being over 10mW/cm³ at the foot and ankle locations. Available power from running was found to be almost 10 times higher than that from walking. Most energy harvester topologies use linear generator approaches that are well suited to fixed-frequency vibrations with sub-millimeter amplitude oscillations. In contrast, body motion is characterized with a wide frequency spectrum and larger amplitudes. A generator prototype based on self-winding wristwatches is deemed to be appropriate for harvesting body motion since it is not limited to operate at fixed-frequencies or restricted displacements. Electromagnetic generation is typically favored because of its slightly higher power output per unit volume. Then, a nonharmonic oscillating rotational energy scavenger prototype is proposed to harness body motion. The electromagnetic generator follows the approach from small wind turbine designs that overcome the lack of a gearbox by using a larger number of coil and magnets arrangements. The device presented here is composed of a rotor with multiple-pole permanent magnets having an eccentric weight and a stator composed of stacked planar coils. The rotor oscillations induce a voltage on the planar coil due to the eccentric mass unbalance produced by body motion. A meso-scale prototype device was then built and evaluated for energy generation. The meso-scale casing and rotor were constructed on PMMA with the help of a CNC mill machine. Commercially available discrete magnets were encased in a 25mm rotor. Commercial copper-coated polyimide film was employed to manufacture the planar coils using MEMS fabrication processes. Jewel bearings were used to finalize the arrangement. The prototypes were also tested at the listed body locations. A meso-scale generator with a 2-layer coil was capable to extract up to 234 µW of power at the ankle while walking at 3mph with a 2cm³ prototype for a power density of 117 µW/cm³. This dissertation presents the analysis of available power from walking and running at different speeds and the development of an unobtrusive miniature energy harvesting generator for body motion. Power generation indicates the possibility of powering devices by extracting energy from body motion.

Effect of reduced oxygen tension and long-term mechanical stimulation on chondrocyte-polymer constructs

We have investigated the influence of long-term confined dynamic compression and surface motion under low oxygen tension on tissue-engineered cell-scaffold constructs. Porous polyurethane scaffolds (8 mm x 4 mm) were seeded with bovine articular chondrocytes and cultured under normoxic (21% O(2)) or hypoxic (5% O(2)) conditions for up to 4 weeks. By means of our joint-simulating bioreactor, cyclic axial compression (10-20%; 0.5 Hz) was applied for 1 h daily with a ceramic ball, which simultaneously oscillated over the construct surface (+/-25 degrees; 0.5 Hz). Culture under reduced oxygen tension resulted in an increase in mRNA levels of type II collagen and aggrecan, whereas the expression of type I collagen was down-regulated at early time points. A higher glycosaminoglycan content was found in hypoxic than in normoxic constructs. Immunohistochemical analysis showed more intense type II and weaker type I collagen staining in hypoxic than in normoxic cultures. Type II collagen gene expression was slightly elevated after short-term loading, whereas aggrecan mRNA levels were not influenced by the applied mechanical stimuli. Of importance, the combination of loading and low oxygen tension resulted in a further down-regulation of collagen type I mRNA expression, contributing to the stabilization of the chondrocytic phenotype. Histological results confirmed the beneficial effect of mechanical loading on chondrocyte matrix synthesis. Thus, mechanical stimulation combined with low oxygen tension is an effective tool for modulating the chondrocytic phenotype and should be considered when chondrocytes or mesenchymal stem cells are cultured and differentiated with the aim of generating cartilage-like tissue in vitro.

Reduced beta-cell mass and altered glucose sensing impair insulin-secretory function in betaIRKO mice

Pancreatic beta-cell-restricted knockout of the insulin receptor results in hyperglycemia due to impaired insulin secretion, suggesting that this cell is an important target of insulin action. The present studies were undertaken in beta-cell insulin receptor knockout (betaIRKO) mice to define the mechanisms underlying the defect in insulin secretion. On the basis of responses to intraperitoneal glucose, approximately 7-mo-old betaIRKO mice were either diabetic (25%) or normally glucose tolerant (75%). Total insulin content was profoundly reduced in pancreata of mutant mice compared with controls. Both groups also exhibited reduced beta-cell mass and islet number. However, insulin mRNA and protein were similar in islets of diabetic and normoglycemic betaIRKO mice compared with controls. Insulin secretion in response to insulin secretagogues from the isolated perfused pancreas was markedly reduced in the diabetic betaIRKOs and to a lesser degree in the nondiabetic betaIRKO group. Pancreatic islets of nondiabetic betaIRKO animals also exhibited defects in glyceraldehyde- and KCl-stimulated insulin release that were milder than in the diabetic animals. Gene expression analysis of islets revealed a modest reduction of GLUT2 and glucokinase gene expression in both the nondiabetic and diabetic mutants. Taken together, these data indicate that loss of functional receptors for insulin in beta-cells leads primarily to profound defects in postnatal beta-cell growth. In addition, altered glucose sensing may also contribute to defective insulin secretion in mutant animals that develop diabetes.

Personal mastery is associated with reduced sympathetic arousal in stressed Alzheimer caregivers

OBJECTIVES: Spousal caregivers of Alzheimer's disease patients are at increased risk for cardiovascular disease, possibly via sympathetic response to stressors and subsequent catecholamine surge. Personal mastery (i.e., belief that one can manage life's obstacles) may decrease psychological and physiological response to stressors. This study examines the relationship between mastery and sympathetic arousal in elderly caregivers, as measured by norepinephrine (NE) reactivity to an acute psychological stressor. DESIGN: Cross-sectional. SETTING: Data were collected by a research nurse in each caregiver's home. PARTICIPANTS: Sixty-nine elderly spousal Alzheimer caregivers (mean age: 72.8 years) who were not taking beta-blocking medication. INTERVENTION: After assessment for mastery and objective caregiving stressors, caregivers underwent an experimental speech task designed to induce sympathetic arousal. MEASUREMENTS: Mastery was assessed using Pearlin's Personal Mastery scale and Alzheimer patient functioning was assessed using the Clinical Dementia Rating Scale, Problem Behaviors Scale, and Activities of Daily Living Scale. Plasma NE assays were conducted using pre- and postspeech blood draws. RESULTS: Multiple regression analyses revealed that mastery was significantly and negatively associated with NE reactivity (B = -9.86, t (61) = -2.03, p = 0.046) independent of factors theoretically and empirically linked to NE reactivity. CONCLUSIONS: Caregivers with higher mastery had less NE reactivity to the stressor task. Mastery may exert a protective influence that mitigates the physiological effects of acute stress, and may be an important target for psychosocial interventions in order to reduce sympathetic arousal and cardiovascular stress among dementia caregivers.

Reduced frontal activation with increasing 2nd language proficiency

The factors influencing the degree of separation or overlap in the neuronal networks responsible for the processing of first and second language are still subject to investigation. This longitudinal study investigates how increasing second language proficiency influences activation differences during lexico-semantic processing of first and second language. Native English speaking exchange students learning German were examined with functional magnetic resonance imaging while reading words in three different languages at two points in time: at the beginning of their stay (day 1) and 5 months later (day 2), when second language proficiency had significantly increased. On day 1, second language words evoked more frontal activation than words from the mother tongue. These differences were diminished on day 2. We therefore conclude that with increasing second language proficiency, lexico-semantic processing of second language words needs less frontal control. Our results demonstrate that lexico-semantic processing of first and second language converges onto similar networks as second language proficiency increases.

High-resolution ultrasound confirms reduced synovial hyperplasia following rituximab treatment in rheumatoid arthritis

OBJECTIVE: To assess the response of RA patients to rituximab (RTX) treatment using a sensitive imaging technique for synovitis. METHODS: Twenty-three RA patients were treated with two 1000-mg infusions of the B-cell depleting antibody, RTX, in an observational protocol. Clinical response was assessed by the European League Against Rheumatism (EULAR) response criteria. High-resolution grey-scale and colour-coded power Doppler (PD) ultrasonography was performed at baseline and 6 months after RTX. The second to fifth MCP and PIP joints were bilaterally examined with joints in a neutral 0 position from a palmar view and scored from 0 to 3. RESULTS: Median disease activity score (DAS28) improved from 5.03 to 3.56 (P = 0.001), which corresponded to a EULAR moderate response in 11 of 23 patients and a EULAR good response in another 6 patients. Improved control of disease activity by RTX was also indicated by tapering of median daily corticosteroid doses from 10 to 5 mg, without flare ups. Mean grey-scale scores correlated with the swollen joint count at baseline (r = 0.484, P = 0.022) and month 6 (r = 0.519, P = 0.011). Mean grey-scale scores improved upon RTX from a 0.90 median (range 0.13-1.87) to 0.75 (range 0.19-1.50, P = 0.023). Frequency of PD positive joints was low (6.1%) at baseline and did not significantly change following RTX treatment. CONCLUSIONS: High-resolution grey-scale ultrasonography (US) examination confirmed reduced synovial hyperplasia, but the applied PD method displayed no significant changes. Therefore, only grey-scale US is recommended in follow-up examinations after RTX treatment.

Detection of pulmonary emboli with CT angiography at reduced radiation exposure and contrast material volume: comparison of 80 kVp and 120 kVp protocols in a matched cohort

The detection rate of pulmonary emboli (PE) with computed tomography angiography (CTA) using either a standard or a low-dose protocol, combining reduced radiation exposure and iodine delivery rate, was retrospectively analyzed in a matched cohort of 120 patients.