Young Control Subjects Research Articles

Improved exercise ventilatory efficiency with nasal compared to oral breathing in cardiac patients.

Objectives: To assess whether nasal breathing improves exercise ventilatory efficiency in patients with heart failure (HF) or chronic coronary syndromes (CCS). Background: Exercise inefficient ventilation predicts disease progression and mortality in patients with cardiovascular diseases. In healthy people, improved ventilatory efficiency with nasal compared to oral breathing was found. Methods: Four study groups were recruited: Patients with HF, patients with CCS, old (age≥45years) and young (age 20-40years) healthy control subjects. After a 3-min warm-up, measurements of 5min with once nasal and once oral breathing were performed in randomized order at 50% peak power on cycle ergometer. Ventilation and gas exchange parameters measured with spiroergometry were analysed by Wilcoxon paired-sample tests and linear mixed models adjusted for sex, height, weight and test order. Results: Groups comprised 15 HF, CCS, and young control and 12 old control. Ventilation/carbon dioxide production ( E/ CO2), ventilation ( E), breathing frequency (fR), and end-tidal oxygen partial pressure (PETO2) were significantly lower and tidal volume and end-tidal carbon dioxide partial pressure (PETCO2) significantly higher during nasal compared to oral breathing in all groups, with large effect sizes for most parameters. For patients with HF, median E/ CO2 was 35% lower, fR 26% lower, and PETCO2 10% higher with nasal compared to oral breathing, respectively. Exercise oscillatory ventilation (EOV) was present in 6 patients and markedly reduced with nasal breathing. Conclusion: Nasal breathing during submaximal exercise significantly improved ventilatory efficiency and abnormal breathing patterns (rapid shallow breathing and EOV) in 80% of our patients with HF and CCS.

Cognitive Impairments After Stroke Do Not Attenuate Explicit Visuomotor Adaptation in Reaching and Savings With the Unaffected Arm

Background Accumulating evidence suggests that motor performance is affected by the cognitive control abilities of the subject. Performance in motor tasks in populations with cognitive deficits such as older adults and subjects with stroke is therefore expected to deteriorate. The goal of this study is to investigate the relationship between cognitive impairments and motor control and learning impairments in a visuomotor adaptation task in subjects with stroke. Methods Twenty-seven post-stroke, 31 age matched controls, and 30 young control subjects completed a sensorimotor adaptation task composed of 2 adaptation blocks separated by a washout block. Explicit learning was assessed by cueing subjects to suppress their strategy. Cognitive assessment was conducted using the Montreal Cognitive Assessment (MoCA) and a verbal learning test. Subjects with stroke performed the task with their unaffected arm. Results Despite the cognitive deterioration, the adaptation and savings of the stroke group and age matched controls were comparable. Adaptation and savings were smaller with respect to the young subjects. Savings was associated with a significant improvement in the explicit component across blocks. Finally, the explicit enhancement between blocks was significantly correlated with the MoCA scores in the stroke group and with the results of the verbal learning test in the young controls. Conclusion The lack of stroke-induced attenuation on adaptation, despite a correlation between cognitive abilities and explicit learning in adaptation, suggests that subjects with stroke have enough cognitive resources to support sensorimotor adaptation. The availability of cognitive resources for motor learning following brain damage could be utilized in the rehabilitation process.

Resting-state oscillations reveal disturbed excitation–inhibition ratio in Alzheimer’s disease patients

An early disruption of neuronal excitation–inhibition (E–I) balance in preclinical animal models of Alzheimer’s disease (AD) has been frequently reported, but is difficult to measure directly and non-invasively in humans. Here, we examined known and novel neurophysiological measures sensitive to E–I in patients across the AD continuum. Resting-state magnetoencephalography (MEG) data of 86 amyloid-biomarker-confirmed subjects across the AD continuum (17 patients diagnosed with subjective cognitive decline, 18 with mild cognitive impairment (MCI) and 51 with dementia due to probable AD (AD dementia)), 46 healthy elderly and 20 young control subjects were reconstructed to source-space. E–I balance was investigated by detrended fluctuation analysis (DFA), a functional E/I (fE/I) algorithm, and the aperiodic exponent of the power spectrum. We found a disrupted E–I ratio in AD dementia patients specifically, by a lower DFA, and a shift towards higher excitation, by a higher fE/I and a lower aperiodic exponent. Healthy subjects showed lower fE/I ratios (< 1.0) than reported in previous literature, not explained by age or choice of an arbitrary threshold parameter, which warrants caution in interpretation of fE/I results. Correlation analyses showed that a lower DFA (E–I imbalance) and a lower aperiodic exponent (more excitation) was associated with a worse cognitive score in AD dementia patients. In contrast, a higher DFA in the hippocampi of MCI patients was associated with a worse cognitive score. This MEG-study showed E–I imbalance, likely due to increased excitation, in AD dementia, but not in early stage AD patients. To accurately determine the direction of shift in E–I balance, validations of the currently used markers and additional in vivo markers of E–I are required.

The relation of the multifocal electroretinographic response to macular layer volume.

To determine the association of the multifocal electroretinographic (mfERG) response amplitude with the volumes of the inner, postreceptor, and photoreceptor retinal layers in the region stimulated by each mfERG element. Sixteen healthy, young adult control subjects were studied. Each of the 103 hexagonal elements of the standard, scaled mfERG were aligned, where possible, with patches of retina imaged using optical coherence tomography. Stimuli falling on the fovea and on the optic nerve head were excluded. Linear mixed-effects modeling was then used to derive estimated coefficients (voltage/volume) for the mfERG response throughout the full 80ms standard epoch. The resulting predicted response amplitudes originating in each layer were then compared to pharmacologically "dissected" mfERGs obtained from other studies in monkey eyes. Across the duration of the response, the amplitude of the modeled contribution from (1)the inner retina was small-to-modest, (2)the postreceptor retina was larger and contained two prominent peaks, and (3)the photoreceptor response was the largest and most closely paralleled the overall (i.e., intact) response, including late-appearing oscillations. The significance of each layer's contribution was greatest when the absolute amplitude of that layer's response was largest. The contribution of the inner retina was maximally significant in the interval between the prominent troughs and peaks of the intact response. The contributions of the postreceptor and photoreceptor responses were maximally significant at the prominent troughs and peaks of the intact response. The results of the model were in good overall agreement with previous interpretations of the cellular contributions to the mfERG. There was also fair agreement with pharmacologically dissected monkey mfERG responses. Thus, the estimations of the contributions of the retinal layers to the mfERG so produced appeared plausible.

Comorbidities and mortality risk in adults younger than 50 years of age with chronic obstructive pulmonary disease

Rationale and objectivePatients with chronic obstructive pulmonary disease (COPD), usually diagnosed after the 6th decade, frequently suffer from comorbidities. Whether COPD patients 50 years or younger (Young COPD) have similar comorbidities with the same frequency and mortality impact as aged-matched controls or older COPD patients is unknown.MethodsWe compared comorbidity number, prevalence and type in 3 groups of individuals with ≥ 10 pack-years of smoking: A Young (≤ 50 years) COPD group (n = 160), an age-balanced control group without airflow obstruction (n = 125), and Old (> 50 years) COPD group (n = 1860). We also compared survival between the young COPD and control subjects. Using Cox proportional model, we determined the comorbidities associated with mortality risk and generated Comorbidomes for the “Young” and “Old” COPD groups.ResultsThe severity distribution by GOLD spirometric stages and BODE quartiles were similar between Young and Old COPD groups. After adjusting for age, sex, and pack-years, the prevalence of subjects with at least one comorbidity was 31% for controls, 77% for the Young, and 86% for older COPD patients. Compared to controls, “Young” COPDs’ had a nine-fold increased mortality risk (p < 0.0001). “Comorbidomes” differed between Young and Old COPD groups, with tuberculosis, substance use, and bipolar disorders being distinct comorbidities associated with increased mortality risk in the Young COPD group.ConclusionsYoung COPD patients carry a higher comorbidity prevalence and mortality risk compared to non-obstructed control subjects. Young COPD differed from older COPD patients by the behavioral-related comorbidities that increase their risk of premature death.

Anterior cingulate cortex metabolites and white matter microstructure: a multimodal study of emergent alcohol use disorder.

Multimodal imaging is increasingly used to address neuropathology associated with alcohol use disorder (AUD). Few studies have investigated relationships between metabolite concentrations and white matter (WM) integrity; currently, there are no such data in AUD. In this preliminary study, we used complementary neuroimaging techniques, magnetic resonance spectroscopy (MRS), and diffusion weighted imaging (DWI), to study AUD neurophysiology. We tested for relationships between metabolites in the dorsal anterior cingulate cortex (dACC) and adjacent WM microstructure in young adult AUD and control (CON) subjects. Sixteen AUD and fourteen CON underwent whole-brain DWI and MRS of the dACC. Outcomes were dACC metabolites, and diffusion tensor metrics of dACC-adjacent WM. Multiple linear regression terms included WM region, group, and region × group for prediction of dACC metabolites. dACC myo-inositol was positively correlated with axial diffusivity in the left anterior corona radiata (p < 0.0001) in CON but not AUD (group effect: p < 0.001; region × group: p < 0.001; Bonferroni-corrected). In the bilateral anterior corona radiata and right genu of the corpus callosum, glutamate was negatively related to mean diffusivity in AUD, but not CON subjects (all model terms: p < 0.05, uncorrected). In AUD subjects, dACC glutamate was negatively correlated with AUD symptom severity. This is likely the first integrative study of cortical metabolites and WM integrity in young individuals with AUD. Differential relationships between dACC metabolites and adjacent WM tract integrity in AUD could represent early consequences of hazardous drinking, and/or novel biomarkers of early-stage AUD. Additional studies are required to replicate these findings, and to determine the behavioral relevance of these results.

Royal jelly alleviates the detrimental effects of aging on immune functions by enhancing the in vitro cellular proliferation, cytokines, and nitric oxide release in aged human PBMCS

Aging strongly delays the immunity. Our research aims to assess the in vitro effects of royal jelly (RJ) on the immune function of aged PBMCs. PBMCs were obtained from 10 healthy aged and young donors by the gradient density centrifugation method and further cultured in RPMI-1640 medium supplemented with or without RJ in the presence of Con A. Cell proliferation was assessed by MTT assay along with the measurement of interleukins, Nitric oxide (NO), Glutathione (GSH), and Malondialdehydes (MDA). Our results showed that RJ improved PBMCs proliferation significantly in the elderly subjects, accompanied by the increase in NO (p=.001) and the release of IL-2, IL-4, and IL-6 cytokines. RJ also increased the intracellular GSH (p= .001) and MDA (p=.001) levels in aged PBMCs. In young subjects, RJ enhanced PBMCs proliferation potency, IL-4, IL-6, GSH, and intracellular MDA levels but with a concomitant decrease in NO and IL-2 cytokine secretion as compared with non RJ-treated cells. In conclusion, RJ restored functions of the aged PBMCs as well as the young control subjects, indicating a beneficial effect on immune status during the aging process. PRACTICAL APPLICATIONS: Royal jelly is a well-known edible dietary compound, used traditionally to treat many diseases throughout the world. Since antiquity, it was shown to have medicinal importance. The immuno-enhancing potential of this food was largely and scientifically established by the lipid and protein fractions. The present study illustrates the anti-aging and stimulatory effects of the fresh RJ whole extract, from local Algerian honey bee: Apis mellifera intermissa, on the immunity of aged men. This study provides the experimental evidence supporting anti-immunosenesence effects of royal jelly. RJ supplementation can be used in the old age management and human age-related complications, especially, associated with the weaknesses of the immune response.

CHOROIDAL VASCULARITY INDEX IN YOUNG CHOROIDEREMIA PATIENTS.

To evaluate choroidal features in young patients affected by choroideremia (CHM). Young CHM patients and control subjects were recruited at the Eye Clinic in Florence. High-resolution choroidal imaging was obtained using swept-source optical coherence tomography with long optical coherence tomography scans (12 × 9 mm optical coherence tomography scans). We considered the subfoveal choroidal area within 9 mm of the optic disk in the horizontal plane and the subfoveal choroidal area within a 3-mm diameter centered over the fovea. The subfoveal choroidal thickness, total choroidal area, luminal area, stromal area, and choroidal vascularity index were assessed using the "ImageJ" software in both groups. Eight patients (16 eyes; mean age, 19.3 ± 5.2 years) and seven control subjects (14 eyes; mean age, 19.0 ± 5.0 years) were included in this study. Best-corrected visual acuity was 20/20 in both eyes of seven CHM patients and in all control subjects and 20/25 in both eyes in one CHM patient. Mean subfoveal choroidal thickness did not differ between CHM patients and control subjects. Luminal area9mm, stromal area9mm, and total choroidal area9mm were reduced in patients compared with the control group. Luminal area3mm, stromal area3mm, and total choroidal area3mm did not differ between patients and control subjects. Choroidal vascularity index9mm and choroidal vascularity index3mm were not different between patients and control subjects. There are no differences in the choroidal vascularity index between young CHM patients and control subjects; this result suggests a simultaneous, proportional impairment of both the stromal and vascular components of the choroid in the early stages of the disease.

Peripheral Maintenance of the Axis SIRT1-SIRT3 at Youth Level May Contribute to Brain Resilience in Middle-Aged Amateur Rugby Players.

Physical exercise performed regularly is known to improve health and to reduce the risk of age-related diseases. Furthermore, there is some evidence of cognitive improvement in physically active middle-aged and older adults. We hypothesized that long-term physically active middle-aged men may have developed brain resilience that can be detected with the analysis of peripheral blood markers. We aimed to analyze the activation of pathways potentially modulated by physical activity in a cohort of healthy amateur rugby players (n = 24) and control subjects with low physical activity (n = 25) aged 45–65 years. We had previously reported neuropsychological improvement in immediate memory responses in the player group compared to the controls. Here, we tested the expression of selected genes of longevity, inflammation, redox homeostasis, and trophic signaling in whole blood mRNA. Analyses were also performed on blood samples of young (aged 15–25 years) control subjects with low physical activity (n = 21). Physical activity and other lifestyle factors were thoroughly recorded with standardized questionnaires. Interestingly, middle-aged control subjects showed lower levels of expression of SIRT1, SIRT3, CAT, and SOD1 than the young controls, although rugby players maintained the expression levels of these genes at a young-like level. Middle-aged players showed lower levels of IL1B than the non-physically active groups. However, there was a tendency towards a decrease in trophic and transduction factors in middle-aged groups as compared to the young controls. A statistical study of Spearman’s correlations supported a positive effect of sporting activity on memory and executive functions, and on peripheral gene expression of SIRT1, SIRT3 and downstream genes, in the middle-aged rugby players. Our results indicate that the SIRT1-SIRT3 axis, and associated neuroprotective signaling, may contribute to the anti-aging resilience of the brain mediated by physical exercise.

Properties of Motor Units of Elbow and Ankle Muscles Decomposed Using High-Density Surface EMG.

Analyses of motor unit activity provide a window to the neural control of motor output. In recent years, considerable advancements in surface EMG decomposition methods have allowed for the discrimination of dozens of individual motor units across a range of muscle forces. While these non-invasive methods show great potential as an emerging technology, they have difficulty discriminating a representative sample of the motor pool. In the present study, we investigate the distribution of recruitment thresholds and motor unit action potential waveforms obtained from high density EMG across four muscles: soleus, tibialis anterior, biceps brachii, and triceps brachii. Ten young and healthy control subjects generated isometric torque ramps between 10-50% maximum voluntary torque during elbow or ankle flexion and extension. Hundreds of motor unit spike trains were decomposed for each muscle across all trials. For lower contraction levels and speeds, surface EMG decomposition discriminated a large number of low-threshold units. However, during contractions of greater speed and torque level the proportion of low threshold motor units decomposed was reduced, resulting in a relatively uniform distribution of recruitment thresholds. The number of motor units decomposed decreased as the contraction level and speed increased. The decomposed units showed a wide range of recruitment thresholds and motor unit action potential amplitudes. In conclusion, although surface EMG decomposition is a useful tool to study large populations of motor units, results of such methods should be interpreted in the context of limitations in sampling of the motor pool.

Acquired immune responses to the seasonal trivalent influenza vaccination in COPD

SummaryEpidemiological data suggest that influenza vaccination protects against all‐cause mortality in chronic obstructive pulmonary disease (COPD) patients. However, recent work has suggested there is a defect in the ability of some COPD patients to mount an adequate humoral response to influenza vaccination. The aim of our study was to investigate humoral and cell‐mediated vaccine responses to the seasonal trivalent influenza vaccination (TIV) in COPD subjects and healthy controls. Forty‐seven subjects were enrolled into the study; 23 COPD patients, 13 age‐matched healthy controls (HC ≥ 50) and 11 young healthy control subjects (YC ≤ 40). Serum and peripheral blood mononuclear cells (PBMC) were isolated pre‐TIV vaccination and at days 7 and 28 and 6 months post‐vaccine for haemagglutinin inhibition (HAI) titre, antigen‐specific T cell and antibody‐secreting cell analysis. The kinetics of the vaccine response were similar between YC, HC and COPD patients and there was no significant difference in antibody titres between these groups at 28 days post‐vaccine. As we observed no disease‐dependent differences in either humoral or cellular responses, we investigated if there was any association of these measures with age. H1N1 (r = −0·4253, P = 0·0036) and influenza B (r = −0·344, P = 0·0192) antibody titre at 28 days negatively correlated with age, as did H1N1‐specific CD4+ T helper cells (r = −0·4276, P = 0·0034). These results suggest that age is the primary determinant of response to trivalent vaccine and that COPD is not a driver of deficient responses per se. These data support the continued use of the yearly trivalent vaccine as an adjunct to COPD disease management.

Reading Acuity as a Predictor of Low-Vision Reading Performance.

PurposeMost people with low vision experience difficulty with reading. Reading assessment can provide guidance for prescription of reading aids and strategies for reading rehabilitation. Here we investigate the effectiveness of letter acuity (LA) and reading acuity (RA) as predictors of low-vision reading performance.MethodsLow-vision subjects (n = 58), young control subjects (n = 52), and older control subjects (n = 14) participated in this study. The low-vision subjects were separated into a Macular group (n = 30) and a Nonmacular group (n = 28) based on whether the diagnoses primarily affected the macular area. LA was measured with the Lighthouse Distance Visual Acuity Chart and RA with the MNREAD Acuity Chart. Reading speeds were obtained across a range of print sizes from the MNREAD test. The MNREAD data were used to estimate required print sizes for three functionally important types of reading for each subject: spot reading (40 words/min [wpm]), fluent reading (80 wpm), and critical print size (required to achieve maximum reading speed).ResultsFor equal values of LA, the Macular group had significantly worse RA than the Nonmacular group. The differences between vision groups, as well as individual variations within groups, were largely explained by the differences in RA. RA is a better predictor than LA for spot reading size, fluent reading size, and critical print size.ConclusionsRA may provide more accurate assessment of reading performance than LA for purposes of low-vision reading rehabilitation.

Dissociating motor learning from recovery in exoskeleton training post-stroke

BackgroundA large number of robotic or gravity-supporting devices have been developed for rehabilitation of upper extremity post-stroke. Because these devices continuously monitor performance data during training, they could potentially help to develop predictive models of the effects of motor training on recovery. However, during training with such devices, patients must become adept at using the new “tool” of the exoskeleton, including learning the new forces and visuomotor transformations associated with the device. We thus hypothesized that the changes in performance during extensive training with a passive, gravity-supporting, exoskeleton device (the Armeo Spring) will follow an initial fast phase, due to learning to use the device, and a slower phase that corresponds to reduction in overall arm impairment. Of interest was whether these fast and slow processes were related.MethodsTo test the two-process hypothesis, we used mixed-effect exponential models to identify putative fast and slow changes in smoothness of arm movements during 80 arm reaching tests performed during 20 days of exoskeleton training in 53 individuals with post-acute stroke.ResultsIn line with our hypothesis, we found that double exponential models better fit the changes in smoothness of arm movements than single exponential models. In contrast, single exponential models better fit the data for a group of young healthy control subjects. In addition, in the stroke group, we showed that smoothness correlated with a measure of impairment (the upper extremity Fugl Meyer score - UEFM) at the end, but not at the beginning, of training. Furthermore, the improvement in movement smoothness due to the slow component, but not to the fast component, strongly correlated with the improvement in the UEFM between the beginning and end of training. There was no correlation between the change of peaks due to the fast process and the changes due to the slow process. Finally, the improvement in smoothness due to the slow, but not the fast, component correlated with the number of days since stroke at the onset of training – i.e. participants who started exoskeleton training sooner after stroke improved their smoothness more.ConclusionsOur results therefore demonstrate that at least two processes are involved in in performance improvements measured during mechanized training post-stroke. The fast process is consistent with learning to use the exoskeleton, while the slow process independently reflects the reduction in upper extremity impairment.

Evaluation of 18F-RO-948 PET for Quantitative Assessment of Tau Accumulation in the Human Brain.

The availability of tau PET radioligands enables quantitative assessment of tau density and distribution in the human brain. We evaluated the kinetics of a novel radioligand, 18F-RO-948 (previously referred to as 18F-RO6958948), and its ability to identify tau positivity in individual patients with mild Alzheimer disease (AD). Methods: Eleven subjects with amyloid-positive mild AD, 5 amyloid-negative older control subjects (OC), and 5 younger control subjects (YC) completed 1 or 2 (4 AD and 5 OC) PET scans with 18F-RO-948 for 90, 120, or 200 min. The kinetics of the radioligand was evaluated with standard compartmental and noncompartmental models (with plasma data in 70% of cases), tissue-reference methods, and SUV ratio. These approaches were applied to assess the ability of 18F-RO-948 to discriminate AD subjects from OC subjects. Results: The plasma reference graphical analysis appeared to be the optimal method of quantification for 18F-RO-948, yielding strictly time-consistent values of distribution volume and distribution volume ratio at 90 min against the analyses at 120 and 200 min. The reference tissue graphical analysis and SUV ratio were cross-validated against plasma reference graphical analysis. Test-retest evaluation showed excellent reproducibility. A proposed novel index of tau load, the regional tau-positive fraction, showed high values in the medial and lateral temporal and parietal regions in AD and successfully separated AD subjects from OC and YC subjects with a significant margin. Conclusion:18F-RO-948 appears to be a promising radioligand for quantitative imaging of tau in the brain of AD patients.

Pigment Epithelium-Derived Factor Plays a Role in Alzheimer\u2019s Disease by Negatively Regulating A\u03b242

Alzheimer’s disease (AD) is the most common cause of dementia. Pigment epithelium-derived factor (PEDF), a unique neurotrophic protein, decreases with aging. Previous reports have conflicted regarding whether the PEDF concentration is altered in AD patients. In addition, the effect of PEDF on AD has not been documented. Here, we tested serum samples of 31 AD patients and 271 normal controls. We found that compared to PEDF levels in young and middle-aged control subjects, PEDF levels were reduced in old-aged controls and even more so in AD patients. Furthermore, we verified that PEDF expression was much lower and amyloid β-protein (Aβ)42 expression was much higher in senescence-accelerated mouse prone 8 (SAMP8) strain mice than in senescence-accelerated mouse resistant 1 (SAMR1) control strain mice. Accordingly, high levels of Aβ42 were also observed in PEDF knockout (KO) mice. PEDF notably reduced cognitive impairment in the Morris water maze (MWM) and significantly downregulated Aβ42 in SAMP8 mice. Mechanistically, PEDF downregulated presenilin-1 (PS1) expression by inhibiting the c-Jun N-terminal kinase (JNK) pathway. Taken together, our findings demonstrate for the first time that PEDF negatively regulates Aβ42 and that PEDF deficiency with aging might play a crucial role in the development of AD.

Age-related microvascular dysfunction: novel insight from near-infrared spectroscopy.

What is the central question of this study? Can near-infrared spectroscopy (NIRS)-derived post-occlusion tissue oxygen saturation recovery kinetics be used to study age-related impairments in microvascular function? What is the main finding and its importance? Using a previously established 5min cuff occlusion protocol, we found that NIRS-derived indices of microvascular function were markedly reduced in elderly compared with young participants. However, when we controlled for the absolute level of vasodilatory stimulus and matched the tissue desaturation level between groups, we found similar responses in young and elderly participants. Overall, these data highlight the important role NIRS can serve in clinical vascular biology, but also establishthe need for assessing tissue ischaemiaduring cuff occlusion protocols. Near-infrared spectroscopy (NIRS) has emerged as a promising tool to evaluate vascular reactivity invivo. Whether this approachcan be used to assess age-related impairments in microvascular function has not been tested. Tissue oxygen saturation (StO2) post-occlusion recovery kinetics were measured in two distinct age groups (<35 and >65years of age) using NIRS placed over the flexor digitorum profundus. Key end-points included the following: (i)the desaturation rate during cuff occlusion; (ii)the lowest StO2 value obtained during ischaemia (StO2min); (iii)StO2 reperfusion rate; (iv)the highest StO2 value reached after cuff release (StO2max); and (v)the reactive hyperaemia area under the curve (AUC). At first, using a conventional 5min cuff occlusion protocol, the elderly participants achieved a much slower rate of oxygen recovery (1.5±0.2 versus 2.5±0.2%s-1 ), lower StO2max (85.2±2.9 versus 92.3±1.5%) and lower reactive hyperaemia AUC (2651.8±307.0 versus 4940.0±375.8%s-1 ). However, owing to a lower skeletal muscle resting metabolic rate, StO2min was also significantly attenuated in the elderly participants compared with the young control subjects (55.7±3.5 versus 41.0±3.4%), resulting in a much lower ischaemic stimulus. To account for this important difference between groups, we then matched the level of tissue ischaemia in a subset of young healthy participants by reducing the cuff occlusion protocol to 3min. Remarkably, when we controlled for tissue ischaemia, we observed no differences in any of the hyperaemic end-points between the young and elderly participants. These data highlight the important role NIRS can serve in vascular biology, but also establish the need for assessing tissue ischaemia during cuff occlusion protocols.

Alignment in the transverse plane, but not sagittal or coronal plane, affects the risk of recurrent patella dislocation.

Abnormalities of lower extremity alignment (LEA) in recurrent patella dislocation (RPD) have been studied mostly by two-dimensional (2D) procedures leaving three-dimensional (3D) factors unknown. This study aimed to three-dimensionally examine risk factors for RPD in lower extremity alignment under the weight-bearing conditions. The alignment of 21 limbs in 15 RPD subjects was compared to the alignment of 24 limbs of 12 healthy young control subjects by an our previously reported 2D-3D image-matching technique. The sagittal, coronal, and transverse alignment in full extension as well as the torsional position of the femur (anteversion) and tibia (tibial torsion) under weight-bearing standing conditions were assessed by our previously reported 3D technique. The correlations between lower extremity alignment and RPD were assessed using multiple logistic regression analysis. The difference of lower extremity alignment in RPD between under the weight-bearing conditions and under the non-weight-bearing conditions was assessed. In the sagittal and coronal planes, there was no relationship (statistically or by clinically important difference) between lower extremity alignment angle and RPD. However, in the transverse plane, increased external tibial rotation [odds ratio (OR) 1.819; 95% confidence interval (CI) 1.282-2.581], increased femoral anteversion (OR 1.183; 95% CI 1.029-1.360), and increased external tibial torsion (OR 0.880; 95% CI 0.782-0.991) were all correlated with RPD. The tibia was more rotated relative to femur at the knee joint in the RPD group under the weight-bearing conditions compared to under the non-weight-bearing conditions (p < 0.05). This study showed that during weight-bearing, alignment parameters in the transverse plane related to the risk of RPD, while in the sagittal and coronal plane alignment parameters did not correlate with RPD. The clinical importance of this study is that the 3D measurements more directly, precisely, and sensitively detect rotational parameters associated with RPD and hence predict risk of RPD. III.

The evaluation of structural remodeling of the left atrium in elderly patients with non-valvular atrial fibrillation

Objective To assess the difference in left atrial properties between elderly and younger control subjects and the role of left atrium remodeling in patients of different ages with atrial fibrillation. Methods A total of 194 patients with non-valvular atrial fibrillation were enrolled from September 2014 to June 2016.Based on age, patients were divided into an elderly group (≥60 years, n=129) and a younger group (<60 years, n=65). We evaluated remodeling parameters for the left atrium using an Ultrasound Cardiography (UCG) system in 125 elder subjects, together with 64 control subjects.All remodeling parameters were recorded, including left atrial diameter (LAD), left atrial square (LAS), left atrial pressure (LAP) and left ventricular end-diastolic dimension (LVEDD). Results The elderly group had more female patients and more patients with persistent atrial fibrillation.Meanwhile, scores of CHA2DS2Vsc and levels of N-terminal pro-brain natriuretic peptide (NT-ProBNP) were significantly increased in elderly patients (both P<0.05). Moreover, the elderly group was associated with increased values of LAD and LAS〔(39.1±4.4)mm vs.(37.1±5.3)mm, P<0.01; and(23.3±4.5)cm2vs.(21.4±4.8)cm2, P<0.01; respectively〕, compared with those in the control group.Spearman’s correlation analysis showed that LAD, LAS and LAP were all markedly related to age (r=0.213, P<0.05; r=-0.175, P<0.05; r=0.170, P<0.05; respectively), persistent onset of atrial fibrillation (r=0.401, P<0.05; r=0.446, P<0.05; r=0.160, P<0.05; respectively), and impaired heart function, measured by left ventricular ejection fraction (r=-0.4371, P<0.05; r=-0.403, P<0.05; r=-0.364, P<0.05; respectively) and NT-ProBNP (r=0.485, P<0.01; r=0.483, P<0.01; r=0.293, P<0.01; respectively). Conclusions Left atrial remodeling properties measured by the UCG system in the elderly with non-valvular atrial fibrillation are more serious than those in mid-aged and young subjects.As a convenient and accurate assessment of remodeling parameters, the UCG system is an excellent option for measuring left atrial remodeling in the elderly population. Key words: Atrial fibrillation; Echocardiography

Real-time Correction of Motion and Imager Instability Artifacts during 3D γ-Aminobutyric Acid-edited MR Spectroscopic Imaging.

Purpose To compare the involuntary head motion, frequency and B0 shim changes, and effects on data quality during real-time-corrected three-dimensional γ-aminobutyric acid-edited magnetic resonance (MR) spectroscopic imaging in subjects with mild cognitive impairment (MCI), patients with Parkinson disease (PD), and young and older healthy volunteers. Materials and Methods In this prospective study, MR spectroscopic imaging datasets were acquired at 3 T after written informed consent was obtained. Translational and rotational head movement, frequency, and B0 shim were determined with an integrated volumetric navigator. Head motion patterns and imager instability were investigated in 33 young healthy control subjects (mean age ± standard deviation, 31 years ± 5), 34 older healthy control subjects (mean age, 67 years ± 8), 34 subjects with MCI (mean age, 72 years ± 5), and 44 patients with PD (mean age, 64 years ± 8). Spectral quality was assessed by means of region-of-interest analysis. Group differences were evaluated with Bonferroni-corrected Mann-Whitney tests. Results Three patients with PD and four subjects with MCI were excluded because of excessive head motion (ie, > 0.8 mm translation per repetition time of 1.6 seconds throughout >10 minutes). Older control subjects, patients with PD, and subjects with MCI demonstrated 1.5, 2, and 2.5 times stronger head movement, respectively, than did young control subjects (1.79 mm ± 0.77) (P < .001). Of young control subjects, older control subjects, patients with PD, and subjects with MCI, 6%, 35%, 38%, and 51%, respectively, moved more than 3 mm during the MR spectroscopic imaging acquisition of approximately 20 minutes. The predominant movements were head nodding and "sliding out" of the imager. Frequency changes were 1.1- and 1.4-fold higher in patients with PD (P = .007) and subjects with MCI (P < .001), respectively, and B0 shim changes were 1.3-, 1.5-, and 1.9-fold higher in older control subjects (P = .005), patients with PD (P < .001), and patients with MCI (P < .001), respectively, compared with those of young control subjects (12.59 Hz ± 2.49, 3.61 Hz · cm-1 ± 1.25). Real-time correction provided high spectral quality in all four groups (signal-to-noise ratio >15, Cramér-Rao lower bounds < 20%). Conclusion Real-time motion and B0 monitoring provides valuable information about motion patterns and B0 field variations in subjects with different predispositions for head movement. Immediate correction improves data quality, particularly in patients who have difficulty avoiding movement. © RSNA, 2017 Online supplemental material is available for this article.

Cognitive function in patients with stable coronary heart disease: Related cerebrovascular and cardiovascular responses.

Chronic exercise has been shown to prevent or slow age-related decline in cognitive functions in otherwise healthy, asymptomatic individuals. We sought to assess cognitive function in a stable coronary heart disease (CHD) sample and its relationship to cerebral oxygenation-perfusion, cardiac hemodynamic responses, and peak compared to age-matched and young healthy control subjects. Twenty-two young healthy controls (YHC), 20 age-matched old healthy controls (OHC) and 25 patients with stable CHD were recruited. Cognitive function assessment included short term—working memory, perceptual abilities, processing speed, cognitive inhibition and flexibility and long-term verbal memory. Maximal cardiopulmonary function (gas exchange analysis), cardiac hemodynamic (impedance cardiography) and left frontal cerebral oxygenation-perfusion (near-infra red spectroscopy) were measured during and after a maximal incremental ergocycle test. Compared to OHC and CHD, YHC had higher peak, maximal cardiac index (CI max), cerebral oxygenation-perfusion (ΔO2 Hb, ΔtHb: exercise and recovery) and cognitive function (for all items) (P<0.05). Compared to OHC, CHD patients had lower peak, CI max, cerebral oxygenation-perfusion (during recovery) and short term—working memory, processing speed, cognitive inhibition and flexibility and long-term verbal memory (P<0.05). peak and CI max were related to exercise cerebral oxygenation-perfusion and cognitive function (P<0.005). Cerebral oxygenation-perfusion (exercise) was related to cognitive function (P<0.005). Stable CHD patients have a worse cognitive function, a similar cerebral oxygenation/perfusion during exercise but reduced one during recovery vs. their aged-matched healthy counterparts. In the all sample, cognitive functions correlated with peak, CI max and cerebral oxygenation-perfusion.