Reliability and validity of the Wolfram Unified Rating Scale (WURS)

Background

Wolfram syndrome (WFS) is a rare, neurodegenerative disease that typically presents with childhood onset insulin dependent diabetes mellitus, followed by optic atrophy, diabetes insipidus, deafness, and neurological and psychiatric dysfunction. There is no cure for the disease, but recent advances in research have improved understanding of the disease course. Measuring disease severity and progression with reliable and validated tools is a prerequisite for clinical trials of any new intervention for neurodegenerative conditions. To this end, we developed the Wolfram Unified Rating Scale (WURS) to measure the severity and individual variability of WFS symptoms. The aim of this study is to develop and test the reliability and validity of the Wolfram Unified Rating Scale (WURS).

Methods

A rating scale of disease severity in WFS was developed by modifying a standardized assessment for another neurodegenerative condition (Batten disease). WFS experts scored the representativeness of WURS items for the disease. The WURS was administered to 13 individuals with WFS (6-25 years of age). Motor, balance, mood and quality of life were also evaluated with standard instruments. Inter-rater reliability, internal consistency reliability, concurrent, predictive and content validity of the WURS were calculated.

Results

The WURS had high inter-rater reliability (ICCs>.93), moderate to high internal consistency reliability (Cronbach’s α = 0.78-0.91) and demonstrated good concurrent and predictive validity. There were significant correlations between the WURS Physical Assessment and motor and balance tests (r_s>.67, p<.03), between the WURS Behavioral Scale and reports of mood and behavior (r_s>.76, p<.04) and between WURS Total scores and quality of life (r_s=-.86, p=.001). The WURS demonstrated acceptable content validity (Scale-Content Validity Index=0.83).

Conclusions

These preliminary findings demonstrate that the WURS has acceptable reliability and validity and captures individual differences in disease severity in children and young adults with WFS.

     

Quantification and recognition of parkinsonian gait from monocular video imaging using kernel-based principal component analysis

Background

The computer-aided identification of specific gait patterns is an important issue in the assessment of Parkinson's disease (PD). In this study, a computer vision-based gait analysis approach is developed to assist the clinical assessments of PD with kernel-based principal component analysis (KPCA).

Method

Twelve PD patients and twelve healthy adults with no neurological history or motor disorders within the past six months were recruited and separated according to their "Non-PD", "Drug-On", and "Drug-Off" states. The participants were asked to wear light-colored clothing and perform three walking trials through a corridor decorated with a navy curtain at their natural pace. The participants' gait performance during the steady-state walking period was captured by a digital camera for gait analysis. The collected walking image frames were then transformed into binary silhouettes for noise reduction and compression. Using the developed KPCA-based method, the features within the binary silhouettes can be extracted to quantitatively determine the gait cycle time, stride length, walking velocity, and cadence.

Results and Discussion

The KPCA-based method uses a feature-extraction approach, which was verified to be more effective than traditional image area and principal component analysis (PCA) approaches in classifying "Non-PD" controls and "Drug-Off/On" PD patients. Encouragingly, this method has a high accuracy rate, 80.51%, for recognizing different gaits. Quantitative gait parameters are obtained, and the power spectrums of the patients' gaits are analyzed. We show that that the slow and irregular actions of PD patients during walking tend to transfer some of the power from the main lobe frequency to a lower frequency band. Our results indicate the feasibility of using gait performance to evaluate the motor function of patients with PD.

Conclusion

This KPCA-based method requires only a digital camera and a decorated corridor setup. The ease of use and installation of the current method provides clinicians and researchers a low cost solution to monitor the progression of and the treatment to PD. In summary, the proposed method provides an alternative to perform gait analysis for patients with PD.

     

Interactions between cognitive and sensory load while planning and controlling complex gait adaptations in Parkinson’s disease

Background

Recent research has argued that removal of relevant sensory information during the planning and control of simple, self-paced walking can result in increased demand on central processing resources in Parkinson’s disease (PD). However, little is known about more complex gait tasks that require planning of gait adaptations to cross over an obstacle in PD.

Methods

In order to understand the interaction between availability of visual information relevant for self-motion and cognitive load, the current study evaluated PD participants and healthy controls while walking toward and stepping over an obstacle in three visual feedback conditions: (i) no visual restrictions; (ii) vision of the obstacle and their lower limbs while in complete darkness; (iii) vision of the obstacle only while in complete darkness; as well as two conditions including a cognitive load (with a dual task versus without a dual task). Each walk trial was divided into an early and late phase to examine changes associated with planning of step adjustments when approaching the obstacle.

Results

Interactions between visual feedback and dual task conditions during the obstacle approach were not significant. Patients with PD had greater deceleration and step time variability in the late phase of the obstacle approach phase while walking in both dark conditions compared to control participants. Additionally, participants with PD had a greater number of obstacle contacts when vision of their lower limbs was not available specifically during the dual task condition. Dual task performance was worse in PD compared to healthy control participants, but notably only while walking in the dark regardless of visual feedback.

Conclusions

These results suggest that reducing visual feedback while approaching an obstacle shifts processing to somatosensory feedback to guide movement which imposes a greater demand on planning resources. These results are key to fully understanding why trips and falls occur in those with PD.

     

The influence of physical activity and yoga on central arterial stiffness

Purpose

Central arterial stiffness is an accepted risk factor for cardiovascular disease. While aerobic activity is associated with reduced stiffness the influence of practicing yoga is unknown. The aims of this study were to: 1) evaluate arterial stiffness in middle-aged adults who regularly practiced yoga, performed regular exercise, or were inactive, 2) evaluate the reproducibility of arterial stiffness measured in the left and right carotid artery and by pulse wave velocity (PWV).

Methods

Twenty six healthy subjects (male and female, 40–65 yrs old) were tested on two separate days. Carotid artery distensibility (DC) was measured with ultrasound. Physical activity was determined by questionnaire.

Results

Yoga and aerobic subjects had similar physical activity levels. Yoga and aerobic groups were not different in either DC (p = 0.26) or PWV (p = 0.21). The sedentary group had lower DC and higher PWV compared to the aerobic and yoga groups (both, p < 0.001). Stiffness measures were reliable day to day (coefficients of variation ~2.5%) and similar between left and right arteries (CV = 2.2%).

Conclusion

Physical activity was a strong predictor of both measures of arterial stiffness, although other factors such as nutritional status need to be accounted for. An independent effect of practicing yoga could not be detected. Stiffness measures were reproducible and left and right sides were consistent with each other.

     

The influence of obesity on calf blood flow and vascular reactivity in older adults

Objective

To determine whether differences in vascular reactivity existed among normal weight, overweight, and obese older men and women, and to examine the association between abdominal fat distribution and vascular reactivity.

Methods

Eighty-seven individuals who were 60 years of age or older (age = 69 ± 7 yrs; mean ± SD) were grouped into normal weight (BMI < 25; n = 30), overweight (BMI ≥ 25 and < 30; n = 28), or obese (BMI ≥ 30; n = 29) categories. Calf blood flow (BF) was assessed by venous occlusion strain-gauge plethysmography at rest and post-occlusive reactive hyperemia.

Results

Post-occlusive reactive hyperemia BF was lower (p = 0.038) in the obese group (5.55 ± 4.67 %/min) than in the normal weight group (8.34 ± 3.89 %/min). Additionally, change in BF from rest to post-occlusion in the obese group (1.93 ± 2.58 %/min) was lower (p = 0.001) than in the normal weight group (5.21 ± 3.59 %/min), as well as the percentage change (75 ± 98 % vs. 202 ± 190 %, p = 0.006, respectively). After adjusting for age, prevalence in hypertension and calf skinfold thickness, change in BF values remained lower (p < 0.05) in obese subjects compared to the normal weight subjects. Lastly, the absolute and percentage change in BF were significantly related to BMI (r = -0.44, p < 0.001, and r = -0.37, p < 0.001, respectively) and to waist circumference (r = -0.36, p = 0.001, and r = -0.32, p = 0.002).

Conclusion

Obesity and abdominal adiposity impair vascular reactivity in older men and women, and these deleterious effects on vascular reactivity are independent of conventional risk factors.

     

Efficacy of repeated intrathecal triamcinolone acetonide application in progressive multiple sclerosis patients with spinal symptoms

Background

There are controversial results on the efficacy of the abandoned, intrathecal predominant methylprednisolone application in multiple sclerosis (MS) in contrast to the proven effectiveness in intractable postherpetic neuralgia.

Methods

We performed an analysis of the efficacy of the application of 40 mg of the sustained release steroid triamcinolone acetonide (TCA). We intrathecally injected in sterile saline dissolved TCA six times within three weeks on a regular basis every third day in 161 hospitalized primary and predominant secondary progressive MS patients with spinal symptoms. The MS patients did not experience an acute onset of exacerbation or recent distinct increased progression of symptoms. We simultaneously scored the MS patients with the EDSS and the Barthel index, estimated the walking distance and measured somatosensory evoked potentials. Additionally the MS patients received a standardized rehabilitation treatment.

Results

EDSS score and Barthel index improved, walking distance increased, latencies of somatosensory evoked potentials of the median and tibial nerves shortened in all MS patients with serial evaluation (p < 0.0001 for all variables). Side effects were rare, five patients stopped TCA application due to onset of a post lumbar puncture syndrome.

Conclusions

Repeated intrathecal TCA application improves spinal symptoms, walking distance and SSEP latencies in progressive MS patients in this uncontrolled study. Future trials should evaluate the long-term benefit of this invasive treatment.

     

Regional changes in reactive hyperemic blood flow during exercise training: time-course adaptations

Background

Few studies have examined the time-course of localized exercise training on regional blood flow in humans. The study examined the influence of handgrip exercise training on forearm reactive hyperemic blood flow and vascular resistance in apparently healthy men.

Methods

Forearm blood flow and vascular resistance were evaluated, in 17 individuals [Age: 22.6 ± 3.5], in both arms, at rest and following 5 minutes of arterial occlusion, using strain gauge plethysmography, prior to training (V1) and every week thereafter (V2-5) for 4 weeks. Handgrip exercise was performed in the non-dominant arm 5 d/wk for 20 minutes at 60% of maximum voluntary contraction, while the dominant arm served as control.

Results

Resting HR, BP, and forearm blood flow and vascular resistance were not altered with training. The trained arm handgrip strength and circumference increased by 14.5% (p = 0.014) and 1.56% (p = 0.03), respectively. ANOVA tests revealed an arms by visit interaction for the trained arm for reactive hyperemic blood flow (p = 0.02) and vascular resistance (p = 0.009). Post-hoc comparison demonstrated increased reactive hyperemic blood flow (p = 0.0013), and decreased post-occlusion vascular resistance (p = 0.05), following the 1^st week of training, with no significant changes in subsequent visits.

Conclusion

The results indicate unilateral improvements in forearm reactive hyperemic blood flow and vascular resistance following 1 week of handgrip exercise training and leveled off for the rest of the study.

     

Occlusion of left atrial appendage affects metabolomic profile: focus on glycolysis,tricarboxylic acid and urea metabolism

Background

Left atrial appendage (LAA) closure (LAAC) by implantation of an occlusion device is an established cardiac intervention to reduce risk of stroke while avoiding intake of oral anticoagulation medication during atrial fibrillation. Cardiac interventions can alter local or systemic gene and protein expression. Effects of LAAC on systemic metabolism have not been studied yet.

Objectives

We aimed to study the effects of interventional LAAC on systemic metabolism.

Methods

Products of glycolysis, tricarboxylic acid and urea metabolism were analyzed by ESI-LC-MS/MS and MS/MS using the AbsoluteIDQ? p180 Kit in plasma of 44 patients undergoing successful interventional LAAC at baseline (T0) and after 6 months (T1).

Results

During follow up, plasma concentrations of several parameters of glycolysis and tricarboxylic acid cycle (TCA) and urea metabolism increased (alanine, hexose, proline, sarcosine), while others decreased (aspartate, glycine, SDMA, serine). Multivariate linear regression analysis showed that time after interventional LAAC was an independent predictor for metabolite changes, including the decrease of SDMA (beta ?0.19, p?<?0.01) and the increase of sarcosine (beta 0.16, p?<?0.01).

Conclusions

Successful interventional LAAC affects different pathways of the metabolome, which are probably related to cardiac remodeling. The underlying mechanisms as well as the long term effects have to be studied in the future.

     

Application of biological age assessment of Chinese population in potential anti-ageing technology

Background

This study aimed to construct a biological age assessment formula for the Chinese population and to explore the effectiveness of double filtration plasmapheresis for anti-ageing and longevity.

Methods

915 subjects were recruited, including 584 (63.8%) males and 331 females (36.2%). Male age was 50.94±10.60 (mean±SD), and female age was 51.20±11.84 (mean±SD). 34 blood markers were detected in the laboratory. The ageing biomarkers were determined by statistical correlation analysis and redundancy analysis, and the biological age assessment formula was established by multiple linear regression analysis. Paired sample T test was used to analyse the elimination effect of double filtration plasmapheresis on aging biomarkers.

Results

Based on the comprehensive blood test and analysis, the ageing biomarkers were screened, and the male and female biological age assessment formulas were established. Then, the elimination of ageing biomarkers by double filtration plasmapheresis was examined. Double filtration plasmapheresis can eliminate ageing biomarkers, with an average of 4.47?years decrease in age for males and 8.36?years for females.

Conclusion

So, biological age provides a scientific tool for assessing ageing, and double filtration plasmapheresis is safe and might be effective for anti-ageing and longevity. However, the effect of plasmapheresis is expected to be transient, so further studies are needed to plan the number and range of the plasmapheresis procedures necessary to consistently lower the parameters under study.

     

A lost opportunity for science: journals promote data sharing in metabolomics but do not enforce it

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.

     

Pseudo current density maps of electrophysiological heart,nerve or brain function and their physical basis

Background

In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.

Methods

The physical basis of these intuitive maps is clarified by means of analytically solvable problems.

Results

Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.

Conclusion

Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.

     

NMR metabolomics of fibroblasts with inherited mitochondrial Complex I mutation reveals treatment-reversible lipid and amino acid metabolism alterations

Introduction

Elucidating molecular alterations due to mitochondrial Complex I (CI) mutations may help to understand CI deficiency (CID), not only in mitochondriopathies but also as it is caused by drugs or associated to many diseases.

Objectives

CID metabolic expression was investigated in Leber’s hereditary optic neuropathy (LHON) caused by an inherited mutation of CI.

Methods

NMR-based metabolomics analysis was performed in intact skin fibroblasts from LHON patients. It used several datasets: one-dimensional ¹H-NMR spectra, two-dimensional ¹H-NMR spectra and quantified metabolites. Spectra were analysed using orthogonal partial least squares-discriminant analysis (OPLS-DA), and quantified metabolites using univariate statistics. The response to idebenone (IDE) and resveratrol (RSV), two agents improving CI activity and mitochondrial functions was evaluated.

Results

LHON fibroblasts had decreased CI activity (??43%, p?<?0.01). Metabolomics revealed prominent alterations in LHON including the increase of fatty acids (FA), polyunsaturated FA and phosphatidylcholine with a variable importance in the prediction (VIP)?>?1 in OPLS-DA, p?<?0.01 in univariate statistics, and the decrease of amino acids (AA), predominantly glycine, glutamate, glutamine (VIP?>?1) and alanine (VIP?>?1, p?<?0.05). In LHON, treatment with IDE and RSV increased CI activity (+?40 and +?44%, p?<?0.05). IDE decreased FA, polyunsaturated FA and phosphatidylcholine (p?<?0.05), but did not modified AA levels. RSV decreased polyunsaturated FA, and increased several AA (VIP?>?1 and/or p?<?0.05).

Conclusion

LHON fibroblasts display lipid and amino acid metabolism alterations that are reversed by mitochondria-targeted treatments, and can be related to adaptive changes. Findings bring insights into molecular changes induced by CI mutation and, beyond, CID of other origins.

     

Number of rare germline CNVs and <Emphasis Type="Italic">TP53</Emphasis> mutation types

Background

The Li-Fraumeni syndrome (LFS), an inherited rare cancer predisposition syndrome characterized by a variety of early-onset tumors, is caused by different highly penetrant germline mutations in the TP53 gene; each separate mutation has dissimilar functional and phenotypic effects, which partially clarifies the reported heterogeneity between LFS families. Increases in copy number variation (CNV) have been reported in TP53 mutated individuals, and are also postulated to contribute to LFS phenotypic variability. The Brazilian p.R337H TP53 mutation has particular functional and regulatory properties that differ from most other common LFS TP53 mutations, by conferring a strikingly milder phenotype.

Methods

We compared the CNV profiles of controls, and LFS individuals carrying either p.R337H or DNA binding domain (DBD) TP53 mutations by high resolution array-CGH.

Results

Although we did not find any significant difference in the frequency of CNVs between LFS patients and controls, our data indicated an increased proportion of rare CNVs per genome in patients carrying DBD mutations compared to both controls (p=0.0002***) and p.R337H (0.0156*) mutants.

Conclusions

The larger accumulation of rare CNVs in DBD mutants may contribute to the reported anticipation and severity of the syndrome; likewise the fact that p.R337H individuals do not present the same magnitude of rare CNV accumulation may also explain the maintenance of this mutation at relatively high frequency in some populations.

     

Metabolomics based markers predict type 2 diabetes in a 14-year follow-up study

Background

The growing field of metabolomics has opened up new opportunities for prediction of type 2 diabetes (T2D) going beyond the classical biochemistry assays.

Objectives

We aimed to identify markers from different pathways which represent early metabolic changes and test their predictive performance for T2D, as compared to the performance of traditional risk factors (TRF).

Methods

We analyzed 2776 participants from the Erasmus Rucphen Family study from which 1571 disease free individuals were followed up to 14-years. The targeted metabolomics measurements at baseline were performed by three different platforms using either nuclear magnetic resonance spectroscopy or mass spectrometry. We selected 24 T2D markers by using Least Absolute Shrinkage and Selection operator (LASSO) regression and tested their association to incidence of disease during follow-up.

Results

The 24 markers i.e. high-density, low-density and very low-density lipoprotein sub-fractions, certain triglycerides, amino acids, and small intermediate compounds predicted future T2D with an area under the curve (AUC) of 0.81. The performance of the metabolic markers compared to glucose was significantly higher among the young (age?<?50 years) (0.86 vs. 0.77, p-value <0.0001), the female (0.88 vs. 0.84, p-value =0.009), and the lean (BMI?<?25 kg/m²) (0.85 vs. 0.80, p-value =0.003). The full model with fasting glucose, TRFs, and metabolic markers yielded the best prediction model (AUC?=?0.89).

Conclusions

Our novel prediction model increases the long-term prediction performance in combination with classical measurements, brings a higher resolution over the complexity of the lipoprotein component, increasing the specificity for individuals in the low risk group.

     

Analysis of p53 expression in partial hydatidiform mole and hydropic abortion

Background

Gestational trophoblastic disease (GTD) is a heterogeneous group of disorders characterized by abnormal trophoblast tissue. Molar and non-molar hydropic placental changes are the most common forms of GTD. Differential diagnosis of GTD is sometimes problematic. Recently, p53 expression was identified as a good marker for distinguishing GTD types.

Aims

Comparison of p53 expression in partial hydatidiform mole (PHM) and hydropic abortion.

Methods

In this prospective cross-sectional study, molar and non-molar hydropic pregnancy specimens were collected. Immunohistochemical staining, based on the Labeled Streptavidin Biotin (LSAB) technique, was carried out on multiple 4 mm paraffin block sections prepared from formalin-fixed trophoblastic tissues. Polymer-based Envision was used to assess p53 tumor suppressor protein immunoreactivity. p53 expression was then compared between both groups.

Results

In the study, 40 patients were included: 20 with confirmed PHM and 20 with hydropic pregnancy. p53 protein was positive in 60% of patients with PHM and 25% of patients with hydropic pregnancy. The p53 positive rate was significantly higher in patients with PHM (p = 0.027). Moreover, patients with PHM had a significantly high grade of staining (p<0.001).

Conclusion

Our findings indicate that immunohistochemical analysis of p53 protein can be used to distinguish PHM and hydropic pregnancy.

     

Biphasic responses of the brachial artery diameter following forearm occlusion: a blunted response in the elderly

Background

The purpose was to examine the temporal response of the brachial artery diameter following 5 minutes of forearm occlusion in young men. A secondary objective was to compare the main features of the temporal pattern between young and old.

Methods

Sixteen young (28 ± 8 yrs) and fifteen older (85 ± 8 yrs) men underwent high-resolution ultrasonography of the brachial artery before and after five minutes of forearm occlusion.

Results

Following release of the pressure cuff the brachial artery diameter exhibits a temporal biphasic response. Initially, there is a significant reduction in brachial diameter (NIL) compared to baseline (BASE), followed by a rapid increase to a PEAK at 41 sec post release. When comparing the magnitude of the decrease in diameter and the Brachial Artery Flow Mediated Dilation (BAFMD) between Young and Old, older subjects demonstrated a blunted response (Magnitude of Decrease: Young: 2.0%; Old: 0.4%, p = 0.015, and BAFMD: Young: 7.7%; Old: 2.3%, p = 0.001). Finally, a significant relationship was noted between the magnitude of decrease and BAFMD (r = -0.44, p = 0.04).

Conclusion

Examination of the temporal response of the brachial artery diameter following 5 minutes of forearm occlusion reveals a biphasic pattern in all participants. Specific features of this pattern are blunted in older adults compared with younger subjects. Finally, the magnitude of the drop in diameter following forearm occlusion correlates with the magnitude of the BAFMD.

     

Nitrous oxide induced subacute combined degeneration with longitudinally extensive myelopathy with inverted V-sign on spinal MRI: a case report and literature review

Background

Nitrous oxide (N2O), a long-standing anesthetic, is also neurotoxic by interfering with the bioavailability of vitamin B12 if abused. A few case studies have reported the neurological and psychiatric complications of N2O.

Case presentation

Here, we reported a patient of N2O induced subacute combined degeneration (SCD) with longitudinally extensive myelopathy with inverted V-sign exhibiting progressive limb paresthesia and unsteady gait.

Conclusions

This case raises the awareness of an important mechanism of neural toxicity of N2O, and clinical physicians should be well recognized this in the field of substance-related disorders.

     

Characterization of ankylosing spondylitis and rheumatoid arthritis using <Superscript>1</Superscript>H NMR-based metabolomics of human fecal extracts

Introduction

The differences in fecal metabolome between ankylosing spondylitis (AS)/rheumatoid arthritis (RA) patients and healthy individuals could be the reason for an autoimmune disorder.

Objectives

The study explored the fecal metabolome difference between AS/RA patients and healthy controls to clarify human immune disturbance.

Methods

Fecal samples from 109 individuals (healthy controls 34, AS 40, and RA 35) were analyzed by ¹H NMR spectroscopy. Data were analyzed with principal component analysis (PCA) and orthogonal projection to latent structure discriminant (OPLS-DA) analysis.

Results

Significant differences in the fecal metabolic profiles could distinguish AS/RA patients from healthy controls but could not distinguish between AS and RA patients. The significantly decreased metabolites in AS/RA patients were butyrate, propionate, methionine, and hypoxanthine. Significantly increased metabolites in AS/RA patients were taurine, methanol, fumarate, and tryptophan.

Conclusion

The metabolome variations in feces indicated AS and RA were two homologous diseases that could not be distinguished by ¹H NMR metabolomics.

     

Bile acid quantification of 20 plasma metabolites identifies lithocholic acid as a putative biomarker in Alzheimer’s disease

Introduction

There is still a clear need for a widely available, inexpensive and reliable method to diagnose Alzheimer’s disease (AD) and monitor disease progression. Liquid chromatography–mass spectrometry (LC-MS) is a powerful analytic technique with a very high sensitivity and specificity.

Objectives

The aim of the present study is to measure concentrations of 20 bile acids using the novel Kit from Biocrates Life Sciences based on LC-MS technique.

Methods

Twenty bile acid metabolites were quantitatively measured in plasma of 30 cognitively healthy subjects, 20 patients with mild cognitive impairment (MCI) and 30 patients suffering from AD.

Results

Levels of lithocholic acid were significantly enhanced in plasma of AD patients (50?±?6 nM, p?=?0.004) compared to healthy controls (32?±?3 nM). Lithocholic acid plasma levels of MCI patients (41?±?4 nM) were not significantly different from healthy subjects or AD patients. Levels of glycochenodeoxycholic acid, glycodeoxycholic acid and glycolithocholic acid were significantly higher in AD patients compared to MCI patients (p?<?0.05). All other cholic acid metabolites were not significantly different between healthy subjects, MCI patients and AD patients. ROC analysis shows an overall accuracy of about 66%. Discriminant analysis was used to classify patients and we found that 15/23 were correctly diagnosed. We further showed that LCA levels increased by about 3.2 fold when healthy subjects converted to AD patients within a 8–9 year follow up period. Pathway analysis linked these changes to a putative toxic cholesterol pathway.

Conclusion

In conclusion, 4 bile acids may be useful to diagnose AD in plasma samples despite limitations in diagnostic accuracy.

     

The effects of aging and activity on muscle blood flow

Background

Our purpose was to determine if aging had an influence on muscle blood flow independent of habitual physical activity levels.

Methods

Blood flow was measured in the femoral artery by Doppler ultrasound after cuff occlusion of 10 minutes. Active and inactive older subjects (73 ± 7 years) were compared to active and inactive young subjects (26 ± 6 years).

Results

Peak blood flow capacity when normalized to lean muscle mass was related to activity level (p < 0.001), but not to age. Specifically, the young active group had higher peak blood flows than the young inactive (p = 0.031) or older inactive (p = 0.005) groups. Resting blood flow and conductance were not significantly different between groups. Mean arterial pressure was significantly higher in the older compared to young group (p = 0.002). Conductance was related to both activity (p = 0.002) and age (p = 0.003). A prolonged time for blood flow to recover was found in the older compared to the young group (p = 0.038) independent of activity status.

Conclusions

The prolonged recovery time in the older subjects may suggest a reduced vascular reactivity associated with increased cardiovascular disease risk. Peak blood flow capacity is maintained in older subjects by physical activity. In summary, maximal flow capacity and prolonged recovery of blood flow are influenced by different mechanisms in young and older active and inactive subjects.