Profiles of cognitive impairment in the continuum from normal cognition to Alzheimer's Clinical Syndrome:Contributions of the Short-term Memory Binding tests

Background: Short-term memory binding (STMB) tests assess conjunctive binding, in which participants should remember the integration of features, such as shapes (or objects) and colors, forming a unique representation in memory. In this study, we investigated two STMB paradigms: change detection (CD) and free recall (FR). Objective: To investigate the cognitive profile in the CD and FR tasks of three diagnostic groups: cognitively unimpaired (CU), mild cognitive impairment (MCI), and Alzheimer's clinical syndrome (ACS). In addition, we aimed to calculate and compare the accuracy of the CD and FR tasks to identify MCI and ACS. Methods: Participants were 24 CU, 24 MCI, and 37 ACS. The cognitive scores of the clinical groups were compared using analysis of variance (ANOVA) and receiver-operating characteristic (ROC) analyses were carried out to verify the accuracy of the STMB tasks. Results: In the CD task, CU was different from MCI and ACS (CU > MCI = ACS), while in the FR task all groups were different (CU > MCI > ACS). The ROC analyses showed an area under the curve (AUC) of 0.855 comparing CU with MCI for the CD task and 0.975 for the FR. The AUC comparing CU and ACS was 0.924 for the CD and 0.973 for the FR task. The FR task showed better accuracy to identify MCI patients, and the same accuracy to detect ACS. Conclusion: The present findings indicate that impairments in CD and FR of bound representations are features of the cognitive profiles of MCI and ACS patients

Vascular relaxation of canine visceral arteries after ischemia by means of supraceliac aortic cross-clamping followed by reperfusion

<p>Abstract</p> <p>Background</p> <p>The supraceliac aortic cross-clamping can be an option to save patients with hipovolemic shock due to abdominal trauma. However, this maneuver is associated with ischemia/reperfusion (I/R) injury strongly related to oxidative stress and reduction of nitric oxide bioavailability. Moreover, several studies demonstrated impairment in relaxation after I/R, but the time course of I/R necessary to induce vascular dysfunction is still controversial. We investigated whether 60 minutes of ischemia followed by 30 minutes of reperfusion do not change the relaxation of visceral arteries nor the plasma and renal levels of malondialdehyde (MDA) and nitrite plus nitrate (NOx).</p> <p>Methods</p> <p>Male mongrel dogs (n = 27) were randomly allocated in one of the three groups: sham (no clamping, n = 9), ischemia (supraceliac aortic cross-clamping for 60 minutes, n = 9), and I/R (60 minutes of ischemia followed by reperfusion for 30 minutes, n = 9). Relaxation of visceral arteries (celiac trunk, renal and superior mesenteric arteries) was studied in organ chambers. MDA and NOx concentrations were determined using a commercially available kit and an ozone-based chemiluminescence assay, respectively.</p> <p>Results</p> <p>Both acetylcholine and calcium ionophore caused relaxation in endothelium-intact rings and no statistical differences were observed among the three groups. Sodium nitroprusside promoted relaxation in endothelium-denuded rings, and there were no inter-group statistical differences. Both plasma and renal concentrations of MDA and NOx showed no significant difference among the groups.</p> <p>Conclusion</p> <p>Supraceliac aortic cross-clamping for 60 minutes alone and followed by 30 minutes of reperfusion did not impair relaxation of canine visceral arteries nor evoke biochemical alterations in plasma or renal tissue.</p

Influence of homogenization conditions on physical properties and antioxidant activity of fully biodegradable pea protein-alpha-tocopherol films

In this study, antioxidant biodegradable films based on pea protein and alpha-tocopherol were successfully developed by solution casting. The effect of both the homogenization conditions (rotor stator and microfluidizer) and the relative humidity (RH) on the microstructure and physical properties (transparency, tensile, oxygen and water vapour barrier properties) of pea protein/alpha-tocopherol-based films was evaluated. The addition of alpha-tocopherol produced minimal changes in the films transparency, while providing them with antioxidant properties and improved water vapour and oxygen barrier properties (up to 30 % in both water vapour and oxygen permeability) when films were at low and intermediate RH. The addition of alpha-tocopherol in microfluidized films gave rise to an increase in their resistance to break and extensibility (up to 27 % in E values) at intermediate and high RH. These results add a new insight into the potential of employing pea protein and alpha-tocopherol in the development of fully biodegradable antioxidant films which are of interest in food packagingThe authors acknowledge the financial support from the Spanish Ministerio de Educacion y Ciencia throughout the project AGL2010-20694, co-funded by FEDER. Author M.J.Fabra is a recipient of a Juan de la Cierva contract from the Spanish Ministerio de Economia y Competitividad.Fabra, MJ.; Jiménez, A.; Talens Oliag, P.; Chiralt, A. (2014). Influence of homogenization conditions on physical properties and antioxidant activity of fully biodegradable pea protein-alpha-tocopherol films. Food and Bioprocess Technology. 7(12):3569-3578. https://doi.org/10.1007/s11947-014-1372-0S35693578712ASTM (1995). Standard test methods for water vapor transmission of materials. Standards Desingnations: E96-95. 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Proposal for a method to estimate nutrient shock effects in bacteria

Plating methods are still the golden standard in microbiology; however, some studies have shown that these techniques can underestimate the microbial concentrations and diversity. A nutrient shock is one of the mechanisms proposed to explain this phenomenon. In this study, a tentative method to assess nutrient shock effects was tested. Findings To estimate the extent of nutrient shock effects, two strains isolated from tap water (Sphingomonas capsulata and Methylobacterium sp.) and two culture collection strains (E. coli CECT 434 and Pseudomonas fluorescens ATCC 13525) were exposed both to low and high nutrient conditions for different times and then placed in low nutrient medium (R2A) and rich nutrient medium (TSA). The average improvement (A.I.) of recovery between R2A and TSA for the different times was calculated to more simply assess the difference obtained in culturability between each medium. As expected, A.I. was higher when cells were plated after the exposition to water than when they were recovered from high-nutrient medium showing the existence of a nutrient shock for the diverse bacteria used. S. capsulata was the species most affected by this phenomenon. This work provides a method to consistently determine the extent of nutrient shock effects on different microorganisms and hence quantify the ability of each species to deal with sudden increases in substrate concentration. <br/

The impact of chronic stress on the rat brain lipidome

Chronic stress is a major risk factor for several human disorders that affect modern societies. The brain is a key target of chronic stress. In fact, there is growing evidence indicating that exposure to stress affects learning and memory, decision making and emotional responses, and may even predispose for pathological processes, such as Alzheimer's disease and depression. Lipids are a major constituent of the brain and specifically signaling lipids have been shown to regulate brain function. Here, we used a mass spectrometry-based lipidomic approach to evaluate the impact of a chronic unpredictable stress (CUS) paradigm on the rat brain in a region-specific manner. We found that the prefrontal cortex (PFC) was the area with the highest degree of changes induced by chronic stress. Although the hippocampus presented relevant lipidomic changes, the amygdala and, to a greater extent, the cerebellum presented few lipid changes upon chronic stress exposure. The sphingolipid and phospholipid metabolism were profoundly affected, showing an increase in ceramide (Cer) and a decrease in sphingomyelin (SM) and dihydrosphingomyelin (dhSM) levels, and a decrease in phosphatidylethanolamine (PE) and ether phosphatidylcholine (PCe) and increase in lysophosphatidylethanolamine (LPE) levels, respectively. Furthermore, the fatty-acyl profile of phospholipids and diacylglycerol revealed that chronic stressed rats had higher 38 carbon(38C)-lipid levels in the hippocampus and reduced 36C-lipid levels in the PFC. Finally, lysophosphatidylcholine (LPC) levels in the PFC were found to be correlated with blood corticosterone (CORT) levels. In summary, lipidomic profiling of the effect of chronic stress allowed the identification of dysregulated lipid pathways, revealing putative targets for pharmacological intervention that may potentially be used to modulate stress-induced deficits.Funding by Fundação para a Ciência e Tecnologia (PTDC/SAU-NMC/118971/2010) and by the North Region Operational Program (ON.2-O Novo Norte), under Quadro de Referência Estratégico Nacional (QREN) and through Fundo Europeu de Desenvolvimento Regional (FEDER). GDP is funded by NIH grants R01 NS056049 and P50 AG008702 (to Scott Small)

Cardiovascular magnetic resonance of myocardial edema using a short inversion time inversion recovery (STIR) black-blood technique: Diagnostic accuracy of visual and semi-quantitative assessment

<p>Abstract</p> <p>Background</p> <p>The short inversion time inversion recovery (STIR) black-blood technique has been used to visualize myocardial edema, and thus to differentiate acute from chronic myocardial lesions. However, some cardiovascular magnetic resonance (CMR) groups have reported variable image quality, and hence the diagnostic value of STIR in routine clinical practice has been put into question. The aim of our study was to analyze image quality and diagnostic performance of STIR using a set of pulse sequence parameters dedicated to edema detection, and to discuss possible factors that influence image quality. We hypothesized that STIR imaging is an accurate and robust way of detecting myocardial edema in non-selected patients with acute myocardial infarction.</p> <p>Methods</p> <p>Forty-six consecutive patients with acute myocardial infarction underwent CMR (day 4.5, +/- 1.6) including STIR for the assessment of myocardial edema and late gadolinium enhancement (LGE) for quantification of myocardial necrosis. Thirty of these patients underwent a follow-up CMR at approximately six months (195 +/- 39 days). Both STIR and LGE images were evaluated separately on a segmental basis for image quality as well as for presence and extent of myocardial hyper-intensity, with both visual and semi-quantitative (threshold-based) analysis. LGE was used as a reference standard for localization and extent of myocardial necrosis (acute) or scar (chronic).</p> <p>Results</p> <p>Image quality of STIR images was rated as diagnostic in 99.5% of cases. At the acute stage, the sensitivity and specificity of STIR to detect infarcted segments on visual assessment was 95% and 78% respectively, and on semi-quantitative assessment was 99% and 83%, respectively. STIR differentiated acutely from chronically infarcted segments with a sensitivity of 95% by both methods and with a specificity of 99% by visual assessment and 97% by semi-quantitative assessment. The extent of hyper-intense areas on acute STIR images was 85% larger than those on LGE images, with a larger myocardial salvage index in reperfused than in non-reperfused infarcts (p = 0.035).</p> <p>Conclusions</p> <p>STIR with appropriate pulse sequence settings is accurate in detecting acute myocardial infarction (MI) and distinguishing acute from chronic MI with both visual and semi-quantitative analysis. Due to its unique technical characteristics, STIR should be regarded as an edema-weighted rather than a purely T2-weighted technique.</p

Cytokine Combination Therapy with Erythropoietin and Granulocyte Colony Stimulating Factor in a Porcine Model of Acute Myocardial Infarction

PurposeErythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) have generated interest as novel therapies after myocardial infarction (MI), but the effect of combination therapy has not been studied in the large animal model. We investigated the impact of prolonged combination therapy with EPO and GCSF on cardiac function, infarct size, and vascular density after MI in a porcine model.MethodsMI was induced in pigs by a 90&nbsp;min balloon occlusion of the left anterior descending coronary artery. 16 animals were treated with EPO+GCSF, or saline (control group). Cardiac function was assessed by echocardiography and pressure-volume measurements at baseline, 1 and 6&nbsp;weeks post-MI. Histopathology was performed 6&nbsp;weeks post-MI.ResultsAt week 6, EPO+GCSF therapy stabilized left ventricular ejection fraction, (41 ± 1% vs. 33 ± 1%, p &lt; 0.01) and improved diastolic function compared to the control group. Histopathology revealed increased areas of viable myocardium and vascular density in the EPO+GCSF therapy, compared to the control. Despite these encouraging results, in a historical analysis comparing combination therapy with monotherapy with EPO or GCSF, there were no significant additive benefits in the LVEF and volumes overtime using the combination therapy.ConclusionOur findings indicate that EPO+GCSF combination therapy promotes stabilization of cardiac function after acute MI. However, combination therapy does not seem to be superior to monotherapy with either EPO or GCSF

Troponin release following endurance exercise: is inflammation the cause? a cardiovascular magnetic resonance study

Background: The aetiology and clinical significance of troponin release following endurance exercise is unclear but may be due to transient myocardial inflammation. Cardiovascular magnetic resonance (CMR) affords us the opportunity to evaluate the presence of myocardial inflammation and focal fibrosis and is the ideal imaging modality to study this hypothesis. We sought to correlate the relationship between acute bouts of ultra endurance exercise leading to cardiac biomarkers elevation and the presence of myocardial inflammation and fibrosis using CMR.Methods: 17 recreation athletes (33.5 +/- 6.5 years) were studied before and after a marathon run with troponin, NTproBNP, and CMR. Specific imaging parameters to look for inflammation included T2 weighted images, and T1 weighted spin-echo images before and after an intravenous gadolinium-DTPA to detect myocardial hyperemia secondary to inflammation. Late gadolinium imaging was performed (LGE) to detect any focal regions of replacement fibrosis.Results: Eleven of the 17 participant had elevations of TnI above levels of cut off for myocardial infarction 6 hrs after the marathon (0.075 +/- 0.02, p = 0.007). Left ventricular volumes were reduced post marathon and a small increase in ejection fraction was noted (64 +/- 1% pre, 67 +/- 1.2% post, P = 0.014). Right ventricular volumes, stroke volume, and ejection fraction were unchanged post marathon. No athlete fulfilled criteria for myocardial inflammation based on current criteria. No regions of focal fibrosis were seen in any of the participants.Conclusion: Exercise induced cardiac biomarker release is not associated with any functional changes by CMR or any detectable myocardial inflammation or fibrosis