A Proposal for a Comprehensive Grading of Parkinson's Disease Severity Combining Motor and Non-Motor Assessments: Meeting an Unmet Need

Background

Non-motor symptoms are present in Parkinson''s disease (PD) and a key determinant of quality of life. The Non-motor Symptoms Scale (NMSS) is a validated scale that allows quantifying frequency and severity (burden) of NMS. We report a proposal for using NMSS scores to determine levels of NMS burden (NMSB) and to complete PD patient classification.

Methods

This was an observational, cross-sectional international study of 935 consecutive patients. Using a distribution of NMSS scores by quartiles, a classification based on levels from 0 (no NMSB at all) to 4 (very severe NMSB) was obtained and its relation with Hoehn and Yahr (HY) staging, motor and health-related quality of life scales was analyzed. Concordance between NMSB levels and grouping based on clinician''s global impression of severity, using categorical regression, was determined. Disability and HRQoL predictors were identified by multiple regression models.

Results

The distribution of motor and QoL scales scores by HY and NMSB levels was significantly discriminative. The difference in the classification of cases for both methods, HY and NMSB, was significant (gamma = 0.45; ASE = 0.032). Concordance between NMSB and global severity-based levels from categorical regression was 91.8%, (kappa_w = 0.97). NMS score was predictor of disability and QoL.

Conclusions

Current clinical practice does not address a need for inclusion of non-motor scores in routine assessment of PD in spite of the overwhelming influence of NMS on disability and quality of life. Our data overcome the problems of “pure motor assessment” and we propose a combined approach with addition of NMSB levels to standard motor assessments.     

Subthalamic Nucleus Deep Brain Stimulation Does Not Improve Visuo-Motor Impairment in Parkinson’s Disease

Objective

To evaluate how bilateral subthalamic nucleus deep brain stimulation (STN-DBS) affects visuo-motor coordination (VMC) in patients with Parkinson’s disease (PD).

Background

VMC involves multi-sensory integration, motor planning, executive function and attention. VMC deficits are well-described in PD. STN-DBS conveys marked motor benefit in PD, but pyscho-cognitive complications are recognized and the effect on VMC is not known.

Methods

Thirteen PD patients with bilateral STN-DBS underwent neurological, cognitive, and mood assessment before VMC testing with optimal DBS stimulation parameters (‘on-stimulation’) and then, on the same day without any medication changes, after DBS silencing and establishing motor function deterioration (‘off-stimulation’). Twelve age-matched healthy controls performed 2 successive VMC testing sessions, with a break of similar duration to that of the PD group. The computer cursor was controlled with a dome-shaped ‘mouse’ hidden from view that minimized tremor effects. Movement duration, hand velocity, tracking continuity, directional control variables, and feedback utilization variables were measured. MANOVA was performed on (1) clinically measured motor function, (2) VMC performance and (3) mood and attention, looking for main and interaction effects of: (1) group (controls/PD), (2) test-order (controls: first/second, PD: on-stimulation/off-stimulation), (3) path (sine/square/circle) and (4) hand (dominant/non-dominant).

Results

Unified PD Rating Scale (UPDRS) Part III worsened off-stimulation versus on-stimulation (mean: 42.3 versus 21.6, p = 0.02), as did finger tapping (p = 0.02), posture-gait (p = 0.01), upper limb function (p<0.001) and backwards digit span (p = 0.02). Stimulation state did not affect mood. PD patients performed worse in non-velocity related VMC variables than controls (F_(5,18) = 8.5, p<0.001). In the control group there were significant main effects of hand (dominant/non-dominant), path (sine/square/circle) and test-order (Test_1/Test_2). In the PD group, hand and path effects, but no test-order (on-stimulation/off-stimulation), were found.

Conclusions

‘Low-level’ clinically-measured motor function responds to STN-DBS but ‘high-level’ motor and cognitive functions relating to VMC may be unresponsive to STN-DBS.     

The combination of homocysteine and C-reactive protein predicts the outcomes of Chinese patients with Parkinson's disease and vascular parkinsonism

Background

The elevation of plasma homocysteine (Hcy) and C-reactive protein (CRP) has been correlated to an increased risk of Parkinson''s disease (PD) or vascular diseases. The association and clinical relevance of a combined assessment of Hcy and CRP levels in patients with PD and vascular parkinsonism (VP) are unknown.

Methodology/Principal Findings

We performed a cross-sectional study of 88 Chinese patients with PD and VP using a clinical interview and the measurement of plasma Hcy and CRP to determine if Hcy and CRP levels in patients may predict the outcomes of the motor status, non-motor symptoms (NMS), disease severity, and cognitive declines. Each patient''s NMS, cognitive deficit, disease severity, and motor status were assessed by the Nonmotor Symptoms Scale (NMSS), Mini-Mental State Examination (MMSE), the modified Hoehn and Yahr staging scale (H&Y), and the unified Parkinson''s disease rating scale part III (UPDRS III), respectively. We found that 100% of patients with PD and VP presented with NMS. The UPDRS III significantly correlated with CRP (P = 0.011) and NMSS (P = 0.042) in PD patients. The H&Y was also correlated with Hcy (P = 0.002), CRP (P = 0.000), and NMSS (P = 0.023) in PD patients. In VP patients, the UPDRS III and H&Y were not significantly associated with NMSS, Hcy, CRP, or MMSE. Strong correlations were observed between Hcy and NMSS as well as between CRP and NMSS in PD and VP.

Conclusions/Significance

Our findings support the hypothesis that Hcy and CRP play important roles in the pathogenesis of PD. The combination of Hcy and CRP may be used to assess the progression of PD and VP. Whether or not anti-inflammatory medication could be used in the management of PD and VP will produce an interesting topic for further research.     

Neurocognition,Insight and Medication Nonadherence in Schizophrenia: A Structural Equation Modeling Approach

Objective

The aim of this study was to examine the complex relationships among neurocognition, insight and nonadherence in patients with schizophrenia.

Methods

Design: Cross-sectional study. Inclusion criteria: Diagnosis of schizophrenia according to the DSM-IV-TR criteria. Data collection: Neurocognition was assessed using a global approach that addressed memory, attention, and executive functions; insight was analyzed using the multidimensional ‘Scale to assess Unawareness of Mental Disorder;’ and nonadherence was measured using the multidimensional ‘Medication Adherence Rating Scale.’ Analysis: Structural equation modeling (SEM) was applied to examine the non-straightforward relationships among the following latent variables: neurocognition, ‘awareness of positive symptoms’ and ‘negative symptoms’, ‘awareness of mental disorder’ and nonadherence.

Results

One hundred and sixty-nine patients were enrolled. The final testing model showed good fit, with normed χ² = 1.67, RMSEA = 0.063, CFI = 0.94, and SRMR = 0.092. The SEM revealed significant associations between (1) neurocognition and ‘awareness of symptoms,’ (2) ‘awareness of symptoms’ and ‘awareness of mental disorder’ and (3) ‘awareness of mental disorder’ and nonadherence, mainly in the ‘attitude toward taking medication’ dimension. In contrast, there were no significant links between neurocognition and nonadherence, neurocognition and ‘awareness of mental disorder,’ and ‘awareness of symptoms’ and nonadherence.

Conclusions

Our findings support the hypothesis that neurocognition influences ‘awareness of symptoms,’ which must be integrated into a higher level of insight (i.e., the ‘awareness of mental disorder’) to have an impact on nonadherence. These findings have important implications for the development of effective strategies to enhance medication adherence.     

Standardized Handwriting to Assess Bradykinesia,Micrographia and Tremor in Parkinson's Disease

Objective

To assess whether standardized handwriting can provide quantitative measures to distinguish patients diagnosed with Parkinson''s disease from age- and gender-matched healthy control participants.

Design

Exploratory study. Pen tip trajectories were recorded during circle, spiral and line drawing and repeated character ‘elelelel’ and sentence writing, performed by Parkinson patients and healthy control participants. Parkinson patients were tested after overnight withdrawal of anti-Parkinsonian medication.

Setting

University Medical Center Groningen, tertiary care, the Netherlands.

Participants

Patients with Parkinson''s disease (n = 10; mean age 69.0 years; 6 male) and healthy controls (n = 10; mean age 68.1 years; 6 male).

Interventions

Not applicable.

Main Outcome Measures

Movement time and velocity to detect bradykinesia and the size of writing to detect micrographia. A rest recording to investigate the presence of a rest-tremor, by frequency analysis.

Results

Mean disease duration in the Parkinson group was 4.4 years and the patients were in modified Hoehn-Yahr stages 1–2.5. In general, Parkinson patients were slower than healthy control participants. Median time per repetition, median velocity and median acceleration of the sentence task and median velocity of the elel task differed significantly between Parkinson patients and healthy control participants (all p<0.0014). Parkinson patients also wrote smaller than healthy control participants and the width of the ‘e’ in the elel task was significantly smaller in Parkinson patients compared to healthy control participants (p<0.0014). A rest-tremor was detected in the three patients who were clinically assessed as having rest-tremor.

Conclusions

This study shows that standardized handwriting can provide objective measures for bradykinesia, tremor and micrographia to distinguish Parkinson patients from healthy control participants.     

Impact of Chikungunya on Health Related Quality of Life Chennai,South India

Background

Chikungunya Virus (CHIKV) infection affects large populations and leads to prolonged and debilitating pain affecting health related quality of life (HRQoL). We assess the impact of CHIKV on HRQoL of clinical CHIKV (C-CHIKV) patients in a suburban locality of Chennai City, South India. Further, we determined factors associated with clinical recovery among C-CHIKV patients.

Methods

We followed-up 403 of 425 adult C-CHIKV cases identified during an outbreak. On the basis of a reassessment of their current clinical status through self-reporting, we categorized them as ‘clinically recovered’ (n = 308) or ‘not recovered’ (n = 95). In the absence of base-line information on HRQoL, we included a comparison group of healthy normal’s recruited by frequency matching for age and sex from the neighbourhood (n = 308). We conducted a comparative cross-sectional study of these three groups and estimated HRQoL scores using SF-36 questionnaire. We tested the differences in the median scores by Kruksall Wallistest. We identified factors associated with ‘recovery’ as compared to not-recovery by calculating Adjusted Odds Ratio (AOR) and 95% Confidence Intervals through multiple regression analysis.

Results

As compared to ‘normals’, we observed a 20 and five-fold reductions in HRQoL scores for C-CHIKV patients ‘not recovered’ and ‘recovered’ respectively. Differences in HRQoL scores for all the domains were statistically significant between three groups (p<0·001). Younger age, male, absence of rashes, affliction of less than five types of joints and two weeks of joint swelling were significantly associated with recovery. HRQoL scores improved with time among those ‘clinically recovered’.

Conclusion

This study provides evidence for sharp reductions in quality of life not only during active C-CHIKV associated illness but also for several months after clinical recovery compared to healthy normals. This has implications for developing intervention programmes in countries with high risk of CHIKV outbreaks.     

Eradication of Helicobacter pylori Infection Improves Levodopa Action,Clinical Symptoms and Quality of Life in Patients with Parkinson's Disease

Background

Previous studies have demonstrated a higher prevalence of Helicobacter pylori (H. pylori) infection in patients with Parkinson''s disease (PD) compared to controls. H. pylori infection affects levodopa absorption and its eradication significantly improves clinical response to levodopa. Here, we studied the prevalence of H. pylori infection and its eradication effects among our PD patients.

Methods

A prospective study involving idiopathic PD patients on levodopa therapy. ¹³C-urea breath test (UBT) was used to detect H. pylori. UBT-positive patients were given standard eradication therapy and followed up at 6 and 12 weeks in an open label single arm design. Repeat UBT was performed at 12 weeks. The UPDRS, PD NMQ, PD NMSS and PDQ-39 were administered at baseline and post-eradication (6 and 12 weeks). Levodopa ‘onset’ time and ON-duration were recorded.

Results

Of 82 patients recruited, 27 (32.9%) had positive UBT. H. pylori-positive patients had significantly poorer total UPDRS (p = 0.005) and PDQ39 (p<0.0001) scores compared to H. pylori-negative patients. At 12 weeks post-eradication, the mean levodopa onset time shortened by 14 minutes (p = 0.011). The mean ON duration time increased by 56 minutes at week 6 (p = 0.041) and 38 minutes at week 12 (p = 0.035). The total UPDRS scores (p<0.0001), scores for parts II (p = 0.001), III (p<0.0001) and IV (p = 0.009) were significantly better. The total PDQ-39 scores (p = 0.001) and subdomains mobility (p = 0.002), ADL (p = 0.001), emotional well being (p = 0.026) and stigma (p = 0.034) significantly improved. The PD NMSQ did not show significant improvement.

Conclusions

H. pylori eradication improved levodopa onset time, ON duration, motor severity and quality of life parameters. Screening and eradication of H. pylori is inexpensive and should be recommended in PD patients, particularly those with erratic response to levodopa.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02112812","term_id":"NCT02112812"}}NCT02112812     

Psychological and physiological effect in humans of touching plant foliage - using the semantic differential method and cerebral activity as indicators

Background

Numerous studies have reported on the healing powers of plants and nature, but there have not been so many instances of experimental research. In particular, there are very few psychological and physiological studies using tactile stimuli. This study examines the psychological and physiological effects of touching plant foliage by using an evaluation profile of the subjects’ impressions and investigating cerebral blood flow.

Methods

The subjects were 14 young Japanese men aged from 21 to 27 years (mean ± standard deviation: 23.6 ± 2.4). With their eyes closed, the subjects touched four different tactile samples including a leaf of natural pothos (Epipremnum aureum). The physiological indices were compared before and after each stimulus. Psychological indices were obtained using a ‘semantic differential’ method.

Results

The fabric stimulus gave people ‘soft’ and ‘rough’ impressions, ‘kind’, ‘peaceful’ and ‘pleasant’ feelings psychologically, and a sense of physiological calm. On the other hand, the metal stimulus gave people ‘cold’, ‘smooth’ and ‘hard’ impressions and an image of something ‘artificial’. The metal stimulus caused a stress response in human cerebral blood flow although its evaluation in terms of ‘pleasant or unpleasant’ was neutral. There were no remarkable differences between the stimuli of natural and artificial pothos compared with other types of stimulus psychologically. However, only the natural pothos stimulus showed a sense of physiological calm in the same appearance as the fabric stimulus.

Conclusions

This study shows that people experience an unconscious calming reaction to touching a plant. It is to be concluded that plants are an indispensable element of the human environment.     

Abnormal Pulmonary Function and Respiratory Muscle Strength Findings in Chinese Patients with Parkinson’s Disease and Multiple System Atrophy–Comparison with Normal Elderly

Background

There have been limited comparative data regarding the investigations on pulmonary and respiratory muscle function in the patients with different parkinsonism disorders such as Parkinson’s disease (PD) and multiple system atrophy (MSA) versus normal elderly. The present study is aiming to characterize the performance of pulmonary function and respiratory muscle strength in PD and MSA, and to investigate the association with severity of motor symptoms and disease duration.

Methods

Pulmonary function and respiratory muscle strength tests were performed in 30 patients with PD, 27 with MSA as well as in 20 age-, sex-, height-, weight-matched normal elderly controls. All the patients underwent United Parkinson’s disease rating scale (UPDRS) or united multiple system atrophy rating scale (UMSARS) separately as diagnosed.

Results

Vital capacity, forced expiratory volume in 1 second and forced vital capacity decreased, residual volume and ratio of residual volume to total lung capacity increased in both PD and MSA groups compared to controls (p<0.05). Diffusing capacity was decreased in the MSA group, compared with PD and normal elderly control groups (p<0.05). Respiratory muscle strength was lower in both PD and MSA groups than in controls (p<0.05). The values representing spirometry function and respiratory muscle strength were found to have a negative linear correlation with mean score of UPDRS-III in PD and mean score of UMSARS-I in MSA. Respiratory muscle strength showed a negative linear correlation with the mean score of UMSARS-II and disease duration in MSA patients.

Conclusions

These findings suggest that respiratory dysfunction is involved in PD and MSA. Respiratory muscle strength is remarkably reduced, and some of the parameters correlate with disease duration and illness severity. The compromised respiratory function in neurodegenerative disorders should be the focus of further researches.     

The Effectiveness of the Cardiovascular Disease Prevention Programme ‘KardioPro’ Initiated by a German Sickness Fund: A Time-to-Event Analysis of Routine Data

Background

Cardiovascular disease is the leading cause of morbidity and mortality in the developed world. To reduce this burden of disease, a German sickness fund (‘Siemens-Betriebskrankenkasse’, SBK) initiated the prevention programme ‘KardioPro’ including primary (risk factor reduction) and secondary (screening) prevention and guideline-based treatment. The aim of this study was to assess the effectiveness of ‘KardioPro’ as it is implemented in the real world.

Methods

The study is based on sickness fund routine data. The control group was selected from non-participants via propensity score matching. Study analysis was based on time-to-event analysis via Cox proportional hazards regression with the endpoint ‘all-cause mortality, acute myocardial infarction (MI) and ischemic stroke (1)’, ‘all-cause mortality (2)’ and ‘non-fatal acute MI and ischemic stroke (3)’.

Results

A total of 26,202 insurants were included, 13,101 participants and 13,101 control subjects. ‘KardioPro’ enrolment was associated with risk reductions of 23.5% (95% confidence interval (CI) 13.0–32.7%) (1), 41.7% (95% CI 30.2–51.2%) (2) and 3.5% (hazard ratio 0.965, 95% CI 0.811–1.148) (3). This corresponds to an absolute risk reduction of 0.29% (1), 0.31% (2) and 0.03% (3) per year.

Conclusion

The prevention programme initiated by a German statutory sickness fund appears to be effective with regard to all-cause mortality. The non-significant reduction in non-fatal events might result from a shift from fatal to non-fatal events.     

Mitochondrial Control Region Alterations and Breast Cancer Risk: A Study in South Indian Population

Background

Mitochondrial displacement loop (D-loop) is the hot spot for mitochondrial DNA (mtDNA) alterations which influence the generation of cellular reactive oxygen species (ROS). Association of D-loop alterations with breast cancer has been reported in few ethnic groups; however none of the reports were documented from Indian subcontinent.

Methodology

We screened the entire mitochondrial D-loop region (1124 bp) of breast cancer patients (n = 213) and controls (n = 207) of south Indian origin by PCR-sequencing analysis. Haplotype frequencies for significant loci, the standardized disequilibrium coefficient (D′) for pair-wise linkage disequilibrium (LD) were assessed by Haploview Software.

Principal Findings

We identified 7 novel mutations and 170 reported polymorphisms in the D-loop region of patients and/or controls. Polymorphisms were predominantly located in hypervariable region I (60%) than in II (30%) of D-loop region. The frequencies of 310‘C’ insertion (P = 0.018), T16189C (P = 0.0019) variants and 310‘C’ins/16189C (P = 0.00019) haplotype were significantly higher in cases than in controls. Furthermore, strong LD was observed between nucleotide position 310 and 16189 in controls (D′ = 0.49) as compared to patients (D′ = 0.14).

Conclusions

Mitochondrial D-loop alterations may constitute inherent risk factors for breast cancer development. The analysis of genetic alterations in the D-loop region might help to identify patients at high risk for bad progression, thereby helping to refine therapeutic decisions in breast cancer.     

Fasting for 24 Hours Heightens Reward from Food and Food-Related Cues

Introduction

We examined the impact of a 24 hour complete fast (vs. fed state) on two measures of food reward: 1) ‘wanting’, as measured by response to food images and by the relative-reinforcing value of food (RRV), and 2) ‘liking’, as measured by response to food images and the hedonic evaluation of foods consumed.

Methods

Utilizing a randomized crossover design, 15 subjects (9 male; 6 female) aged 28.6±4.5 yrs with body mass index 25.3±1.4 kg/m² were randomized and counterbalanced to normal feeding (FED) and 24-hour fast (FASTED) conditions. Trait characteristics were measured with the Three Factor Eating Questionnaire. Two computer tasks measured food reward: 1) RRV progressive ratio task, 2) explicit ‘liking’ and ‘wanting’ (Leeds Food Preference Questionnaire, LFPQ). Also measured were ad libitum energy intake (EI; buffet) and food ‘liking’ (visual analogue scale) of personalized stimuli.

Results

There were no significant anthropometric changes between conditions. Appetite scores, hedonic ratings of ‘liking’, and ad libitum EI all significantly increased under the FASTED condition (p<0.05). Under the FASTED condition there were significant increases in the RRV of snack foods; similarly, explicit ‘wanting’ and ‘liking’ significantly increased for all food categories. ‘Liking’ of sweet foods remained high across-meals under FASTED, but savory foods decreased in hedonic saliency.

Conclusion

Relative to a fed state, we observed an increase in hedonic ratings of food, the rewarding value of food, and food intake after a 24 hr fast. Alliesthesia to food and food cues is suggested by heightened hedonic ratings under the FASTED condition relative to FED.     

Participation during First Social Encounters in Schizophrenia

Background

Patients with a diagnosis of schizophrenia are socially excluded. The aim of this study was to investigate how patients participate in first encounters with unfamiliar healthy participants, who are unaware of their diagnosis.

Methods

Patterns of participation were investigated during interactions involving three-people. Three conversation roles were analysed: (i) speaker, (ii) primary recipient- focus of the speaker’s attention and (iii) secondary recipient- unaddressed individual. Twenty patient interactions (1 patient, 2 healthy controls) and 20 control interactions (3 healthy participants) were recorded and motion captured in 3D. The participation of patients and their partners, in each conversation role, was compared with controls at the start, middle and end of the interaction. The relationship between patients’ participation, their symptoms and the rapport others experienced with them was also explored.

Results

At the start of the interaction patients spoke less (ß = −.639, p = .02) and spent more time as secondary recipient (ß = .349, p = .02). Patients’ participation at the middle and end of the interaction did not differ from controls. Patients’ partners experienced poorer rapport with patients who spent more time as a primary recipient at the start of the interaction (Rho(11) = −.755, p<.01). Patients’ participation was not associated with symptoms.

Conclusion

Despite their increased participation over time, patients’ initial participation appears to be associated with others’ experience of rapport with them. Thus, the opening moments of patients’ first encounters appear to be interpersonally significant. Further investigation of patient and others’ behaviour during these critical moments is warranted in order to understand, and possibly develop interventions to address, the difficulties schizophrenia patients experience here.     

galign: A Tool for Rapid Genome Polymorphism Discovery

Background

Highly parallel sequencing technologies have become important tools in the analysis of sequence polymorphisms on a genomic scale. However, the development of customized software to analyze data produced by these methods has lagged behind.

Methods/Principal Findings

Here I describe a tool, ‘galign’, designed to identify polymorphisms between sequence reads obtained using Illumina/Solexa technology and a reference genome. The ‘galign’ alignment tool does not use Smith-Waterman matrices for sequence comparisons. Instead, a simple algorithm comparing parsed sequence reads to parsed reference genome sequences is used. ‘galign’ output is geared towards immediate user application, displaying polymorphism locations, nucleotide changes, and relevant predicted amino-acid changes for ease of information processing. To do so, ‘galign’ requires several accessory files easily derived from an annotated reference genome. Direct sequencing as well as in silico studies demonstrate that ‘galign’ provides lesion predictions comparable in accuracy to available prediction programs, accompanied by greater processing speed and more user-friendly output. We demonstrate the use of ‘galign’ to identify mutations leading to phenotypic consequences in C. elegans.

Conclusion/Significance

Our studies suggest that ‘galign’ is a useful tool for polymorphism discovery, and is of immediate utility for sequence mining in C. elegans.     

Leaf trait dissimilarities between Dutch elm hybrids with a contrasting tolerance to Dutch elm disease

Background and Aims

Previous studies have shown that Ophiostoma novo-ulmi, the causative agent of Dutch elm disease (DED), is able to colonize remote areas in infected plants of Ulmus such as the leaf midrib and secondary veins. The objective of this study was to compare the performances in leaf traits between two Dutch elm hybrids ‘Groeneveld’ and ‘Dodoens’ which possess a contrasting tolerance to DED. Trait linkages were also tested with leaf mass per area (LMA) and with the reduced Young''s modulus of elasticity (MOE) as a result of structural, developmental or functional linkages.

Methods

Measurements and comparisons were made of leaf growth traits, primary xylem density components, gas exchange variables and chlorophyll a fluorescence yields between mature plants of ‘Groeneveld’ and ‘Dodoens’ grown under field conditions. A recently developed atomic force microscopy technique, PeakForce quantitative nanomechanical mapping, was used to reveal nanomechanical properties of the cell walls of tracheary elements such as MOE, adhesion and dissipation.

Key Results

‘Dodoens’ had significantly higher values for LMA, leaf tissue thickness variables, tracheary element lumen area (A), relative hydraulic conductivity (RC), gas exchange variables and chlorophyll a fluorescence yields. ‘Groeneveld’ had stiffer cell walls of tracheary elements, and higher values for water-use efficiency and leaf water potential. Leaves with a large carbon and nutrient investment in LMA tended to have a greater leaf thickness and a higher net photosynthetic rate, but LMA was independent of RC. Significant linkages were also found between the MOE and some vascular traits such as RC, A and the number of tracheary elements per unit area.

Conclusions

Strong dissimilarities in leaf trait performances were observed between the examined Dutch elm hybrids. Both hybrids were clearly separated from each other in the multivariate leaf trait space. Leaf growth, vascular and gas exchange traits in the infected plants of ‘Dodoens’ were unaffected by the DED fungus. ‘Dodoens’ proved to be a valuable elm germplasm for further breeding strategies.     

Retinal Thickness Measurement Obtained with Spectral Domain Optical Coherence Tomography Assisted Optical Biopsy Accurately Correlates with Ex Vivo Histology

Background

This study determines ‘correlation constants’ between the gold standard histological measurement of retinal thickness and the newer spectral-domain optical coherence tomography (SD-OCT) technology in adult C57BL/6 mice.

Methods

Forty-eight eyes from adult mice underwent SD-OCT imaging and then were histologically prepared for frozen sectioning with H&E staining. Retinal thickness was measured via 10x light microscopy. SD-OCT images and histological sections were standardized to three anatomical sites relative to the optic nerve head (ONH) location. The ratios between SD-OCT to histological thickness for total retinal thickness (TRT) and six sublayers were defined as ‘correlation constants’.

Results

Mean (± SE) TRT for SD-OCT and histological sections was 210.95 µm (±1.09) and 219.58 µm (±2.67), respectively. The mean ‘correlation constant’ for TRT between the SD-OCT and histological sections was 0.96. The retinal thickness for all sublayers measured by SD-OCT vs. histology were also similar, the ‘correlation constant’ values ranged from 0.70 to 1.17. All SD-OCT and histological measurements demonstrated highly significant (p<0.01) strong positive correlations.

Conclusion

This study establishes conversion factors for the translation of ex vivo data into in vivo information; thus enhancing the applicability of SD-OCT in translational research.     

Detection of Subclinical Atherosclerosis in Asymptomatic Subjects Using Ultrasound Radiofrequency-Tracking Technology

Objective

Atherosclerosis is a chronic and systemic disease and its developmental process involves the synergism of multiple risk factors such as hypertension, dyslipidemia, diabetes, obesity and smoking. The diagnosis of subclinical atherosclerosis is essential for strategic guidance towards suitable treatments and efficient prevention against acute cardiovascular events. This study employed ultrasound radiofrequency (RF) tracking technology to characterize human carotid arteries in vivo in terms of intima-media thickness (IMT) and artery stiffness, and evaluated the statistical correlation between carotid IMT and stiffness, and the number of risk factors for atherosclerosis.

Methods

A total of 160 asymptomatic subjects were enrolled. Ultrasound RF-tracking technology was employed to acquire carotid IMT and stiffness parameters: maximum IMT (^MAXIMT), RF Quality IMT (^RFQIMT), distensibility coefficient (), compliance coefficient (), index, index and local pulse wave velocity (). The subjects were categorized in four groups in terms of the number of risk factors: ‘zero’, ‘single’, ‘double’, and ‘multiple’, and statistical analyses of carotid IMT and stiffness parameters were performed between these different groups.

Results

The subjects (n = 145) with ^MAXIMT smaller than 1.0 mm matched the IMT criteria for non-atherosclerosis and were named as NA-subjects. Spearman’s rho correlation analysis of the whole group and the NA-subjects both showed that ^MAXIMT correlated positively with ^RFQIMT, , , and , and negatively with and (p<0.01). The analysis of covariance of NA-subjects showed significant differences between subjects with and without risk factors, and also showed significant differences between the ‘zero’, ‘single’, ‘double’, and ‘multiple’ groups.

Conclusions

The carotid IMT and stiffness parameters obtained by the ultrasound RF-tracking technology were demonstrated to possess significant statistical correlation with the number of risk factors from 160 subjects, and these anatomical and mechanical parameters may potentially be used together with the IMT criteria to support subclinical atherosclerosis diagnosis.     

Variability of Stepping during a Virtual Reality Paradigm in Parkinson’s Disease Patients with and without Freezing of Gait

Background

Freezing of gait is a common and debilitating symptom affecting many patients with advanced Parkinson’s disease. Although the pathophysiology of freezing of gait is not fully understood, a number of observations regarding the pattern of gait in patients with this symptom have been made. Increased ‘Stride Time Variability’ has been one of the most robust of these features. In this study we sought to identify whether patients with freezing of gait demonstrated similar fluctuations in their stepping rhythm whilst performing a seated virtual reality gait task that has recently been used to demonstrate the neural correlate of the freezing phenomenon.

Methods

Seventeen patients with freezing and eleven non-freezers performed the virtual reality task twice, once whilst ‘On’ their regular Parkinsonian medication and once in their practically defined ‘Off’ state.

Results

All patients displayed greater step time variability during their ‘Off’ state assessment compared to when medicated. Additionally, in the ‘Off’ state, patients with freezing of gait had greater step time variability compared to non-freezers. The five steps leading up to a freezing episode in the virtual reality environment showed a significant increase in step time variability although the final three steps preceding the freeze were not characterized by a progressive shortening of latency.

Conclusions

The results of this study suggest that characteristic features of gait disturbance observed in patients with freezing of gait can also be demonstrated with a virtual reality paradigm. These findings suggest that virtual reality may offer the potential to further explore the freezing phenomenon in Parkinson’s disease.