Baseline Differences in Long-term Survivors and Nonsurvivors of the Colorado/Columbia Fetal Implant Trial.

OBJECTIVE: This study is based on long-term follow-up of participants in a randomized double-blind sham surgery-controlled trial (1995-1999) designed to determine the effectiveness of implantation of human embryonic mesencephalic tissue containing dopamine neuron precursors into the brains of patients with advanced Parkinson's disease (PD). We investigated differences between long-term survivors and nonsurvivors at baseline in order to contribute to information regarding optimal patient selection for upcoming stem cell trials. METHOD: Forty participants were randomly assigned to receive either neural implantation or sham surgery. Thirty-four patients who ultimately received the implant were followed periodically with the most recent assessment occurring in 2015-2016. Demographic information, neurological measures, positron emission tomography (PET) imaging, neuropsychological assessments, and a personality assessment were included in the current analyses. T-tests were used to compare survivors and nonsurvivors. Logistic regression analyses examined predictors of survivorship. RESULTS: Five of six survivors were female. They were younger than nonsurvivors (p = .03) and more neuropsychologically "intact" across a broad range of cognitive areas (significance levels ranged from <.001 to .045). There were no differences between survivors and nonsurvivors off medications at baseline on neurological or PET assessments. Survivors reported more "Openness to Experience" (p = .004) than nonsurvivors. Using empirically derived predictor variables, results of logistic regression analyses indicated that Animal Naming (cognitive task) and Openness to Experience (personality variable) were the strongest predictors of survivorship. CONCLUSIONS: Variables to consider when selecting participants for future cell-based therapies include being "intact" neuropsychologically, level of Openness to Experience, younger age, and inclusion of women.

Persistent dyskinesias in patients with fetal tissue transplantation for Parkinson disease.

Cell transplants are being developed for patients with Parkinson disease (PD) who have insufficient benefit with standard medical treatment. We describe the clinical features of five patients who developed persistent dyskinesias after fetal dopaminergic tissue transplantation. All had levodopa-induced dyskinesias preoperatively. We implanted fetal mesencephalic dopaminergic tissue into the putamina bilaterally in 34 patients with advanced PD. They were not immunosuppressed. Five of 34 patients (15%) developed troublesome choreic or dystonic dyskinesias that persisted despite lowering or discontinuing medications. Attempts to treat the involuntary movements with amantadine, clozapine, anticholinergics, dopamine depletors and other medicines had limited success. Metyrosine eliminated dyskinesias but led to the parkinsonian "off" state. Increasing the dose of levodopa worsened the dyskinesias. Three patients required placement of pallidal stimulators, bilaterally in two and unilaterally in one patient who had only contralateral dyskinesias. The two with the bilateral stimulators had improvement in dyskinesias. The patient with the unilateral pallidal stimulator had a substantial reduction of the dyskinesias, but attempts to treat residual "off" symptoms with levodopa were limited by worsening dyskinesias. Although the number of patients developing these persistent dyskinesias was small, these five patients had dramatic improvement after transplant. As a group, they had milder Parkinson signs at baseline and improved to the point of having minimal parkinsonism, with reduction or elimination of levodopa therapy prior to developing persistent dyskinesias. These involuntary movements establish the principle that fetal dopaminergic tissue transplants can mimic the effects of levodopa, not only in reducing bradykinesia, but also in provoking dyskinesias.

Molecular Verification of the UK National Collection of Cultivated Liriope and Ophiopogon Plants.

A collection of cultivated Liriope and Ophiopogon plants was established in 1996-1998 and subsequently hosted at a horticultural college. Uncertainties about the identification of the accessions, compounded by potential errors in propagation and labelling have led to waning confidence in the identities of the plants in the collection. The potential for using DNA barcoding to determine the species identities of the accessions was investigated. The DNA barcode regions of the plastid ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit gene (rbcL) and nuclear ribosomal internal transcribed spacer (nrITS) were amplified. DNA sequence analysis allowed the sequences of the accessions to be compared to reference sequences in public databases. A simple haplotype map of the characteristic polymorphic positions in the rbcL regions was used to clearly distinguish between the two genera and assign Ophiopogon accessions to individual species or sub-groups of species. The ITS sequence data confirmed these genus and species assignations and provided greater resolution to distinguish between closely related species. The combination of two DNA barcodes allowed most of the accessions to be assigned to individual species. This molecular verification confirmed the identity of about 70% of the accessions, with the remaining 30% demonstrating a range of mistaken identities at the species and genus levels.

Involuntary Thumb Flexion on Neurological Examination: An Unusual Form of Upper Limb Dystonia in the Faroe Islands.

Background: The prevalence of dystonia varies worldwide. A prior report suggested a high prevalence of focal dystonia in the Faroese population, possibly reflecting a founder effect. During standardized neurological examination as part of an ongoing neuroepidemiologic study in the Faroe Islands, we noted an unusual phenomenon of thumb flexion during repetitive hand movements in a subset of subjects and sought to define its phenomenology. Methods: We requested commentary from a panel of dystonia experts regarding the phenomenology of the movements. These experts reviewed the videotaped neurological examination. Results: Among the experts, dystonia was the leading diagnosis. Alternate causes were considered, but deemed less likely. Discussion: Diagnosis of dystonia requires careful clinical assessment and consideration of associated features. We report a novel form of dystonia, not previously described to our knowledge, in this isolated population. Further studies of dystonia prevalence in the Faroe Islands are merited to characterize its burden in this population and its specific clinical characteristics.

Progressive Supranuclear Palsy, Corticobasal Degeneration, and Multiple System Atrophy.

PURPOSE OF REVIEW: Patients who have parkinsonian features, especially without tremor, that are not responsive to levodopa, usually have one of these three major neurodegenerative disorders rather than Parkinson disease: progressive supranuclear palsy (PSP), multiple system atrophy (MSA), or corticobasal degeneration (CBD). Each of these disorders eventually develops signs and symptoms that distinguish it from idiopathic Parkinson disease, but these may not be present at disease onset. Although these conditions are not generally treatable, it is still important to correctly diagnose the condition as soon as possible. RECENT FINDINGS: In recent years, it has been increasingly recognized that the symptoms of these diseases do not accurately predict the pathology, and the pathology does not accurately predict the clinical syndrome. Despite this, interest has grown in treating these diseases by targeting misfolded tau (in the case of PSP and CBD) and misfolded α-synuclein (in the case of MSA). SUMMARY: Knowledge of the characteristic signs and symptoms of PSP, MSA, and CBD are essential in diagnosing and managing patients who have atypical parkinsonian syndromes.

Intra-individual study of mindfulness: ecological momentary perspective in post-surgical lung cancer patients.

The period of recovery following a lung-cancer surgery presents unique challenges and psychological demands. The study utilized ecological momentary assessments (EMA) to repeatedly sample mindfulness states in a sample of mindfulness-untrained individuals following hospital discharge. Intra- and inter- individual variability was assessed to examine cancer patients' natural capacity to exhibit mindfulness states during two weeks of recovery. Fifty nine stage I lung cancer patients (61% women, mean age = 66.1, SD = 7.9) completed EMA twice a day for two weeks. Mean level of mindfulness in the sample was low and equaled .49 (SD = .51) on the 5 point scale, with older participants being less likely to endorse mindful states. Net variability in mindfulness, defined as the person-based standard deviation in momentary scores, equaled .42 (SD = .26), ranging for 0 to 1.3 and indicating very modest variability for most participants. Results of the multi-level variance partitioning model revealed 41.4% of variance in mindfulness scores at the inter-individual, 2.4% on the temporal (i.e., .2% weekly and 2.2% daily), and 56.2% on the momentary levels. Findings indicate that, for cancer patients recovering from surgery, the innate ability to exhibit mindfulness is limited. From the methodological standpoint, consideration of intra-individual variability has implications for conceptualization and design of EMA studies.

Feasibility Test of a Community-Relevant Intervention Designed to Promote African American Participation in Translational, Breast Cancer Disparities Research: Know About Health Options for Women (Know HOW).

There are marked racial differences in breast cancer, the second leading cause of death among US women. Understanding the causes of these differences is essential to eliminate breast cancer inequities. More prevalent in African American than in Caucasian women, metabolic syndrome has been associated with breast cancer outcomes. Further research is needed to understand metabolic syndrome's role in breast cancer disparities, thus novel strategies to increase minority participation in research are important. We embedded two approaches (comprehensive, focused) to increase African American participation in breast cancer research in a state-wide service program and pilot tested both approaches in rural African American women. We conducted three comprehensive and three focused outreach programs (n = 48) and assessed research participation through consent and actual provision of data for four types of data: survey, anthropometric, blood, and mammography records. The majority of participants provided written consent for all data collection procedures (96 % survey; 92 % anthropometric; 94 %, blood; 100 % mammography). There were no between group differences in consent rates. There was variation in the overall proportion of participants who provided data (96 % survey; 92 % anthropometric; 73 % blood; 40 % mammography). Women in the comprehensive approach were less likely to return for a scheduled mammogram than women in the focused approach (19 % vs 64 %, p = 0.0236). Both outreach programs promoted African American engagement in research. Differences in the provision of data by type may have been due to participant burden (i.e., time required to provide data). Study designs that embed research in service programs have promise to increase minority research participation.

Video Review of Baseline Performance on Global Ratings in a Double-Blind Placebo Surgery Trial.

BACKGROUND: A randomized controlled double-blind sham surgery trial was conducted to determine the effectiveness of implantation of human embryonic dopamine neurons into the putamen of patients with advanced Parkinson's disease (PD). The present analyses determined whether patients viewing a video of them performing motor activities off medications at baseline would affect self-ratings 12 months later on the Global Rating Scale (GRS). OBJECTIVES: To examine changes in GRS scores pre- and post-video review for the total sample; to examine differences in scores between actual implant and sham groups, as well as perceived groups pre- and post-video review; to examine differences among four subgroups of patients based on actual and perceived treatment (i.e., actual implant/perceived implant). METHODS: Forty participants were recruited and randomly assigned to receive either neural implantation or sham surgery. The primary outcome variable was a one-item GRS ranging from -3 (much worse since surgery) to +3 (much improved since surgery). At 12 months (before the blind was lifted) patients rated themselves on the GRS before and after viewing the baseline video. RESULTS: Total sample GRS scores improved after the video (P = .001). There were no differences between the actual implant and sham groups before or after the video, but there were differences between perceived groups at both times (P < .001). Among subgroups, improvement after the video was found only in the group receiving the implant but who thought sham (P = .011). CONCLUSIONS: When self-ratings are an outcome variable, review of baseline videos is recommended before making comparative ratings.

Genus-Specific Real-Time PCR and HRM Assays to Distinguish Liriope from Ophiopogon Samples.

Liriope and Ophiopogon species have a long history of use as traditional medicines across East Asia. They have also become widely used around the world for ornamental and landscaping purposes. The morphological similarities between Liriope and Ophiopogon taxa have made the taxonomy of the two genera problematic and caused confusion about the identification of individual specimens. Molecular approaches could be a useful tool for the discrimination of these two genera in combination with traditional methods. Seventy-five Liriope and Ophiopogon samples from the UK National Plant Collections of Ophiopogon and Liriope were analyzed. The 5' end of the DNA barcode region of the gene for the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (rbcLa) was used for the discrimination of the two genera. A single nucleotide polymorphism (SNP) between the two genera allowed the development of discriminatory tests for genus-level identification based on specific PCR and high-resolution melt curve (HRM) assays. The study highlights the advantage of incorporating DNA barcoding methods into plant identification protocols and provides simple assays that could be used for the quality assurance of commercially traded plants and herbal drugs.

Motor fluctuations due to interaction between dietary protein and levodopa in Parkinson's disease.

BACKGROUND: The modulation of levodopa transport across the blood brain barrier by large neutral amino acids is well documented. Protein limitation and protein redistribution diets may improve motor fluctuations in patients with Parkinson's disease but the pharmacokinetics and pharmacodynamics of levodopa and amino acids are highly variable. METHODS: Clinical records of 1037 Parkinson's disease patients were analyzed to determine the proportion of patients with motor fluctuations related to protein interaction with levodopa. Motor fluctuations due to protein interaction with levodopa were defined as dietary protein being associated with (i) longer time to levodopa effectiveness, (ii) reduced benefit or duration of benefit, (iii) dose failures or (iv) earlier wearing off from a previously effective dose. Dose failures, sudden, painful or behavioral wearing-off periods, gait freezing, nausea, hallucinations, orthostasis, and dyskinesias were taken as markers of motor fluctuations, disease severity, and levodopa side effects potentially influenced by protein. RESULTS: 5.9 % of Parkinson's disease patients on levodopa, and 12.4 % with motor fluctuations on levodopa correlated their fluctuations with the relative timing of levodopa and protein intake. These patients were younger at disease onset, had worse motor fluctuations and had a higher incidence of family members with Parkinson's disease. Early wearing off or decreased dose efficacy were most commonly associated with protein interaction. 60 % of patients who modified their diets had weight loss. CONCLUSIONS: This study suggests that clinically significant protein interaction with levodopa may occur mostly in a subset of Parkinson's disease patients with earlier disease onset and those with familial disease.

Improvement of Primary Writing Tremor in Parkinson's Disease with Carbidopa/Levodopa.

BACKGROUND: Primary writing tremor is a task-specific phenomenon that has been described as variants of essential tremor or dystonia. PHENOMENOLOGY SHOWN: We describe the case of a 63-year-old female who initially had primary writing tremor, later developed Parkinson's disease, and once initiated on carbidopa/levodopa had improvement in her parkinsonism and her writing tremor. EDUCATIONAL VALUE: As neither essential tremor nor typical brachial dystonia respond to carbidopa/levodopa, our case documents that at least some cases of primary writing tremor are not variants of either dystonia or essential tremor.

Community Engagement in Health-Related Research: A Case Study of a Community-Linked Research Infrastructure, Jefferson County, Arkansas, 2011-2013.

BACKGROUND: Underrepresentation of racial minorities in research contributes to health inequities. Important factors contributing to low levels of research participation include limited access to health care and research opportunities, lack of perceived relevance, power differences, participant burden, and absence of trust. We describe an enhanced model of community engagement in which we developed a community-linked research infrastructure to involve minorities in research both as participants and as partners engaged in issue selection, study design, and implementation. COMMUNITY CONTEXT: We implemented this effort in Jefferson County, Arkansas, which has a predominantly black population, bears a disproportionate burden of chronic disease, and has death rates above state and national averages. METHODS: Building on existing community-academic partnerships, we engaged new partners and adapted a successful community health worker model to connect community residents to services and relevant research. We formed a community advisory board, a research collaborative, a health registry, and a resource directory. OUTCOME: Newly formed community-academic partnerships resulted in many joint grant submissions and new projects. Community health workers contacted 2,665 black and 913 white community residents from December 2011 through April 2013. Eighty-five percent of blacks and 88% of whites were willing to be re-contacted about research of potential interest. Implementation challenges were addressed by balancing the needs of science with community needs and priorities. INTERPRETATION: Our experience indicates investments in community-linked research infrastructure can be fruitful and should be considered by academic health centers when assessing institutional research infrastructure needs.

Comparison of clinical features in pathologically confirmed PSP and MSA patients followed at a tertiary center.

BACKGROUND/OBJECTIVES: The clinical diagnosis of progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) remains challenging due to heterogeneity of the diseases. AIMS: Here we compared the clinical features of PSP and MSA to gain insight into their diagnosis and prognosis, particularly the prognostic value of down-gaze palsy latency in PSP progression. METHODS: We reviewed clinical features of pathologically confirmed 10 PSP and 13 MSA patients, incidentally matched in age-at-onset, gender, and disease duration, followed at Columbia University Medical Center during 1994-2009. RESULTS: The final antemortem diagnosis was incorrect in 30% of PSP (all lacking down-gaze palsy) and 23% of MSA patients. Falls in the first year of the disease, pyramidal involvement and freezing of gait during the course were similar between PSP and MSA. Ataxia and apraxia were in 50% of the PSP patients. Parkinsonism responsive to levodopa treatment was in 30% of the PSP (all with resting tremor) and 50% of the MSA patients. Dysautonomia in MSA could occur as early as 3 years preceding the motor symptoms, with 46% within the first year of the motor onset, but 15% did not have dysautonomia in life. The latency of down-gaze palsy and urogenital dysfunction and MMSE scores at first visit in PSP, and the latency of falls and wheelchair confinement in MSA were all associated with the disease progression. CONCLUSIONS: We confirmed most of the previously published characterizations, and identified for the first time the prognostic value of down-gaze palsy latency in PSP progression.

Usefulness of the Audience Response System in training lay health advisors for chronic disease prevention.

Lay health promoters (LHPs) have been successful in preventing disease. Given the complexity of health interventions, a crucial component that is necessary for LHPs' success is the training they receive. Engaging methods have the potential to increase LHPs' learning and efficacy to implement health interventions. The Audience Response System (ARS) has successfully facilitated interactive learning in several settings, but has not been used to train LHPs. This paper describes how the ARS was used in LHP training to implement a complex behavioral intervention, reports the training results, and serves as a model for others who work with LHPs.

A unique interactive cognitive behavioral training program for front-line cancer care professionals.

For between one third and one half of all cancer survivors, disturbances in mood and cognition do not end with the conclusion of treatment. Recognizing this problem, the Institute of Medicine emphasized in its 2008 report, the importance of addressing psychosocial issues, such as distress, to providing quality cancer care. The National Cancer Institute (NCI) has recognized that there is a severe lack of trained professionals who can address these needs. In response to this need, an interactive training program was developed and implemented to teach frontline cancer care professionals Cognitive Behavioral Therapy (CBT) skills. This training includes a structured curriculum, centered around a 3-day training workshop that includes didactic discussion, small group interactive sessions, role playing, post course support, and follow-up evaluation. Four of the planned eight workshops have been conducted thus far and indicate successful recruitment and implementation of a unique training model related to the CBT skills learned.