Trajectories of pain over 6 years in early Parkinson's disease: ICICLE-PD.

INTRODUCTION: Pain is a common non-motor symptom in Parkinson's disease (PD), affecting up to 85% of patients. The frequency and stability of pain over time has not been extensively studied. There is a paucity of high-quality studies investigating pain management in PD. To develop interventions, an understanding of how pain changes over the disease course is required. METHODS: One hundred and fifty-four participants with early PD and 99 age-and-sex-matched controls were recruited as part of a longitudinal study (Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation in PD, ICICLE-PD). Pain data were collected at 18-month intervals over 72 months in both groups using the Nonmotor Symptom Questionnaire (NMSQ), consisting of a binary yes/no response. Two questions from the Parkinson's Disease Questionnaire (PDQ-39) were analysed for the PD group only. RESULTS: Unexplained pain was common in the PD group and occurred more frequently than in age-matched controls. 'Aches and pains' occurred more frequently than 'cramps and muscle spasms' at each time point (p < 0.001) except 54 months. CONCLUSIONS: This study shows that pain is prevalent even in the early stages of PD, yet the frequency and type of pain fluctuates as symptoms progress. People with PD should be asked about their pain at clinical consultations and given support with describing pain given the different ways this can present.

Short-interval intracortical inhibition to the biceps brachii is present during arm cycling but is not different than a position- and intensity-matched tonic contraction.

We have previously shown that supraspinal excitability is higher during arm cycling than a position- and intensity-matched tonic contraction. The present study sought to determine if short-interval intracortical inhibition (SICI) was present during arm cycling and if so, if the amount of SICI was different from an intensity-matched tonic contraction. SICI was assessed using conditioning stimuli (CS) of 70 and 90% of active motor threshold (AMT) and a test stimulus (TS) of 120% AMT at an interstimulus interval (ISI) of 2.5 ms. SICI was elicited in all participants; on average (i.e., cycling and tonic contraction grouped) test MEP amplitudes were reduced by 64.2% (p < 0.001) and 62.8% (p = 0.001) following conditioning stimuli of 70% and 90% AMT, respectively. There was no significant difference in extent of SICI between tasks (p = 0.360). These data represent the novel finding that SICI is present during arm cycling, a motor output partially mediated by spinal interneuronal networks. The amount of SICI, however, was not different from that during a position- and intensity-matched tonic contraction, suggesting that SICI is not likely a cortical mechanism contributing to higher supraspinal excitability during arm cycling compared to tonic contraction.

Intensity matters: effects of cadence and power output on corticospinal excitability during arm cycling are phase and muscle dependent.

The present study investigated the effects of cadence and power output on corticospinal excitability to the biceps (BB) and triceps brachii (TB) during arm cycling. Supraspinal and spinal excitability were assessed using transcranial magnetic stimulation (TMS) of the motor cortex and transmastoid electrical stimulation (TMES) of the corticospinal tract, respectively. Motor-evoked potentials (MEPs) elicited by TMS and cervicomedullary motor-evoked potentials (CMEPs) elicited by TMES were recorded at two positions during arm cycling corresponding to mid-elbow flexion and mid-elbow extension (i.e., 6 and 12 o'clock made relative to a clock face, respectively). Arm cycling was performed at combinations of two cadences (60 and 90 rpm) at three relative power outputs (20, 40, and 60% peak power output). At the 6 o'clock position, BB MEPs increased ~11.5% as cadence increased and up to ~57.2% as power output increased ( P < 0.05). In the TB, MEPs increased ~15.2% with cadence ( P = 0.013) but were not affected by power output, while CMEPs increased with cadence (~16.3%) and power output (up to ~19.1%, P < 0.05). At the 12 o'clock position, BB MEPs increased ~26.8% as cadence increased and up to ~96.1% as power output increased ( P < 0.05), while CMEPs decreased ~29.7% with cadence ( P = 0.013) and did not change with power output ( P = 0.851). In contrast, TB MEPs were not different with cadence or power output, while CMEPs increased ~12.8% with cadence and up to ~23.1% with power output ( P < 0.05). These data suggest that the "type" of intensity differentially modulates supraspinal and spinal excitability in a manner that is phase- and muscle dependent. NEW & NOTEWORTHY There is currently little information available on how changes in locomotor intensity influence excitability within the corticospinal pathway. This study investigated the effects of arm cycling intensity (i.e., alterations in cadence and power output) on corticospinal excitability projecting to the biceps and triceps brachii during arm cycling. We demonstrate that corticospinal excitability is modulated differentially by cadence and power output and that these modulations are dependent on the phase and the muscle examined.

Do you see what I see? Mobile eye-tracker contextual analysis and inter-rater reliability.

Mobile eye-trackers are currently used during real-world tasks (e.g. gait) to monitor visual and cognitive processes, particularly in ageing and Parkinson's disease (PD). However, contextual analysis involving fixation locations during such tasks is rarely performed due to its complexity. This study adapted a validated algorithm and developed a classification method to semi-automate contextual analysis of mobile eye-tracking data. We further assessed inter-rater reliability of the proposed classification method. A mobile eye-tracker recorded eye-movements during walking in five healthy older adult controls (HC) and five people with PD. Fixations were identified using a previously validated algorithm, which was adapted to provide still images of fixation locations (n = 116). The fixation location was manually identified by two raters (DH, JN), who classified the locations. Cohen's kappa correlation coefficients determined the inter-rater reliability. The algorithm successfully provided still images for each fixation, allowing manual contextual analysis to be performed. The inter-rater reliability for classifying the fixation location was high for both PD (kappa = 0.80, 95% agreement) and HC groups (kappa = 0.80, 91% agreement), which indicated a reliable classification method. This study developed a reliable semi-automated contextual analysis method for gait studies in HC and PD. Future studies could adapt this methodology for various gait-related eye-tracking studies.

fNIRS response during walking - Artefact or cortical activity? A systematic review.

This systematic review aims to (i) evaluate functional near infrared spectroscopy (fNIRS) walking study design in young adults, older adults and people with Parkinson's disease (PD); (ii) examine signal processing techniques to reduce artefacts and physiological noise in fNIRS data; and (iii) provide evidence-based recommendations for fNIRS walking study design and signal analysis techniques. An electronic search was undertaken. The search request detailed the measurement technique, cohort and walking task. Thirty-one of an initial yield of 73 studies satisfied the criteria. Protocols and methods for removing artefacts and noise varied. Differences in fNIRS signals between studies were found in rest vs. walking, speed of walking, usual vs. complex walking and easy vs. difficult tasks. In conclusion, there are considerable technical and methodological challenges in conducting fNIRS studies during walking which can introduce inconsistencies in study findings. We provide recommendations for the construction of robust methodologies and suggest signal processing techniques implementing a theoretical framework accounting for the physiology of haemodynamic responses.

Accuracy and re-test reliability of mobile eye-tracking in Parkinson's disease and older adults.

Mobile eye-tracking is important for understanding the role of vision during real-world tasks in older adults (OA) and people with Parkinson's disease (PD). However, accuracy and reliability of such devices have not been established in these populations. We used a novel protocol to quantify accuracy and reliability of a mobile eye-tracker in OA and PD. A mobile eye-tracker (Dikablis) measured the saccade amplitudes of 20 OA and 14 PD on two occasions. Participants made saccades between targets placed 5°, 10° and 15° apart. Impact of visual correction (glasses) on saccadic amplitude measurement was also investigated in 10 OA. Saccade amplitude accuracy (median bias) was -1.21° but a wide range of bias (-7.73° to 5.81°) was seen in OA and PD, with large vertical saccades (15°) being least accurate. Reliability assessment showed a median difference between sessions of <1° for both groups, with poor to good relative agreement (Spearman rho: 0.14 to 0.85). Greater accuracy and reliability was observed in people without visual correction. Saccade amplitude can be measured with variable accuracy and reliability using a mobile eye-tracker in OA and PD. Human, technological and study-specific protocol factors may introduce error and are discussed along with methodological recommendations.

Peering into the literature: A systematic review of the roles of people who inject drugs in harm reduction initiatives.

BACKGROUND: People who inject drugs have been central to the development of harm reduction initiatives. Referred to as peer workers, peer helpers, or natural helpers, people with lived experience of drug use leverage their personal knowledge and skills to deliver harm reduction services. Addressing a gap in the literature, this systematic review focuses on the roles of people who inject drugs in harm reduction initiatives, how programs are organized, and obstacles and facilitators to engaging people with lived experience in harm reduction programs, in order to inform practice and future research. METHODS: This systematic review included searches for both peer reviewed and gray literature. All titles and abstracts were screened by two reviewers. A structured data extraction tool was developed and utilized to systematically code information concerning peer roles and participation, program characteristics, obstacles, and facilitators. RESULTS: On the basis of specific inclusion criteria 164 documents were selected, with 127 peer-reviewed and 37 gray literature references. Data extraction identified key harm reduction program characteristics and forms of participation including 36 peer roles grouped into five categories, as well as obstacles and facilitators at systemic, organizational, and individual levels. CONCLUSIONS: Research on harm reduction programs that involve people with lived experience can help us better understand these approaches and demonstrate their value. Current evidence provides good descriptive content but the field lacks agreed-upon approaches to documenting the ways peer workers contribute to harm reduction initiatives. Implications and ten strategies to better support peer involvement in harm reduction programs are identified.

Biomechanical demands differentiate transitioning vs. continuous stair ascent gait in older women.

BACKGROUND: Stair ascent mechanics change with age, but little is known about the differing functional demands of transitioning and continuous ascent. Work investigating the risky transition from gait to ascent is sparse, and the strategies that older adults adopt to achieve these demanding tasks have not been investigated. METHODS: This study compared the biomechanics of a 2-step transitional (floor-to-step2) and continuous ascent cycle (step1-to-step3) and investigated the role of limb preference in relation to dynamometer-derived knee strength during this transition. A biomechanical analysis of 36 women (60-83 years) ascending a 3-step staircase was conducted. FINDINGS: The 2-step transitioning cycle was completed quicker, with a larger range of motion, increased forces, larger knee flexor and dorsiflexor moments and ankle powers (P≤0.05), but reduced hip and knee flexion, smaller hip extensor moments and hip and knee powers compared to continuous ascent. During the transition, 44% of the participants demonstrated a consistent limb preference. In these cases large between-limb extensor strength differences existed (13.8%) and 71% of these participants utilised the stronger limb to execute the 2-step transitional cycle. INTERPRETATION: The preferential stronger-limb 2-step transitioning strategy conflicts with previous recommendations of a stronger lead limb for frail/asymmetric populations. Our findings suggest that most healthy older women with large between-limb differences utilise the stronger limb to achieve the considerable propulsion required to redirect momentum during the 2-step transition. The biomechanical demands of ascent, relative to limb strength, can inform exercise programmes by targeting specific muscle groups to help older adults maintain/improve general functioning.

Alterations in gait speed and age do not fully explain the changes in gait mechanics associated with healthy older women.

Older adults exhibit modified gait patterns compared to the young, adopting movement strategies in response to changes in musculoskeletal function. Investigating the functional mobility of older women is particularly important because of their increased life expectancy and greater falls risk compared to men. We explored the relationships between gait parameters and age in healthy older women whilst accounting for declining gait speeds. Kinematic and kinetic data were collected from thirty-nine women (60-83 years) whilst walking at a comfortable cadence. Regression analysis assessed the capacity of gait speed and age to explain the variance in gait associated with older age. Speed explained the majority of variance in many gait parameters. By including age in the regression, the total explained variance (R2) for foot clearance (70%), ankle plantarflexion angle (30%), peak ankle plantarflexor moment (58%), and hip power generation (56%) were significantly (p<0.05) greater than for speed alone. Nonetheless, changes in speed and age did not fully explain the variance in gait mechanics associated with older age and other contributing factors must exist. Losses of 1.2%/year in gait speed were predicted by age, exceeding previous predictions of -0.7%/year. Furthermore, the accumulation of apparently small decreases of 0.2 cm/year in peak foot-to-ground clearance has clinical implications and offers insight into the mechanisms by which gait becomes hazardous in older age.

Simultaneous detection of viral and bacterial enteric pathogens using the Seeplex® Diarrhea ACE detection system.

A panel of 223 faecal samples was analysed to determine the clinical utility of the Seeplex® Diarrhea ACE Detection multiplex PCR system (Seeplex system; Seegene, Korea), a qualitative multiplexing PCR technology that enables simultaneous multi-pathogen detection of four viruses and/or ten bacteria associated with acute gastroenteritis. Conventional diagnostic methods and a norovirus-specific multiplex real-time RT­PCR detected 98 pathogens in 96 samples. The Seeplex system detected 81 pathogens in 75 samples. All samples positive for adenovirus, norovirus, Campylobacter spp., Escherichia coli O157, Shigella spp. or Vibrio spp. were detected by the Seeplex system. Rotavirus, Clostridium difficile toxin B, and Salmonella spp. were not detected in 12.5%, 50% and 15.8% of samples, respectively. Additional multiple infections were detected in 19 samples by the Seeplex system. The Seeplex system provides significant additional diagnostic capability for the syndromic diagnosis of acute gastroenteritis with increased sensitivity for the majority of pathogens.

Comparative genomic and proteomic analysis of high grade glioma primary cultures and matched tumor in situ.

Developing targeted therapies for high grade gliomas (HGG), the most common primary brain tumor in adults, relies largely on glioma cultures. However, it is unclear if HGG tumorigenic signaling pathways are retained under in-vitro conditions. Using array comparative genomic hybridization and immunohistochemical profiling, we contrasted the epidermal and platelet-derived growth factor receptor (EGFR/PDGFR) in-vitro pathway status of twenty-six primary HGG cultures with the pathway status of their original HGG biopsies. Genomic gains or amplifications were lost during culturing while genomic losses were more likely to be retained. Loss of EGFR amplification was further verified immunohistochemically when EGFR over expression was decreased in the majority of cultures. Conversely, PDGFRα and PDGFRß were more abundantly expressed in primary cultures than in the original tumor (p<0.05). Despite these genomic and proteomic differences, primary HGG cultures retained key aspects of dysregulated tumorigenic signaling. Both in-vivo and in-vitro the presence of EGFR resulted in downstream activation of P70s6K while reduced downstream activation was associated with the presence of PDGFR and the tumor suppressor, PTEN. The preserved pathway dysregulation make this glioma model suitable for further studies of glioma tumorigenesis, however individual culture related differences must be taken into consideration when testing responsiveness to chemotherapeutic agents.