Providing genetic testing and genetic counseling for Parkinson's disease to the community.

PURPOSE: To evaluate the feasibility and impact of offering genetic testing and counseling to patients with Parkinson's disease (PD), with the potential to enroll in gene-targeted clinical trials and improve clinical care. METHODS: A multicenter, exploratory pilot study at 7 academic hospital sites in the United States tracked enrollment and randomized participants to receive results and genetic counseling at local sites or by genetic counselors, remotely. Follow-up surveys measured participant/provider satisfaction, knowledge, and psychological impact. RESULTS: From September 5, 2019 to January 4, 2021, 620 participants were enrolled and 387 completed outcome surveys. There were no significant differences in outcomes between local and remote sites, with both arms reporting high knowledge and satisfaction scores (>80%). Notably, 16% of those tested had reportable PD gene variants (pathogenic/likely pathogenic/risk allele). CONCLUSION: Local clinicians, as well as genetic counselors, with educational support as needed, can effectively return genetic results for PD as we observed favorable outcome measures in both groups. Increasing access to PD genetic testing and counseling is urgent; this can inform future efforts to integrate genetic testing and counseling into clinical care for all those with PD.

COVID-19 manifestations in people with Parkinson's disease: a USA cohort.

BACKGROUND: With the explosion of COVID-19 globally, it was unclear if people with Parkinson's disease (PD) were at increased risk for severe manifestations or negative outcomes. OBJECTIVES: To report on people with PD who had suspected or confirmed COVID-19 to understand how COVID-19 manifested in PD patients. METHODS: We surveyed PD patients who reported COVID-19 to their Movement Disorders specialists at Columbia University Irving Medical Center and respondents from an online survey administered by the Parkinson's Foundation that assessed COVID-19 symptoms, general clinical outcomes and changes in motor and non-motor PD symptoms. RESULTS: Forty-six participants with PD and COVID-19 were enrolled. Similar to the general population, the manifestations of COVID-19 among people with PD were heterogeneous ranging from asymptomatic carriers (1/46) to death (6/46). The most commonly reported COVID-19 symptoms were fever/chills, fatigue, cough, weight loss, and muscle pain. Worsening and new onset of motor and non-motor PD symptoms during COVID-19 illness were also reported, including dyskinesia, rigidity, balance disturbances, anxiety, depression, and insomnia. CONCLUSION: We did not find sufficient evidence that PD is an independent risk factor for severe COVID-19 and death. Larger studies with controls are required to understand this further. Longitudinal follow-up of these participants will allow for observation of possible long-term effects of COVID-19 in PD patients.

Lipidomics Prediction of Parkinson's Disease Severity: A Machine-Learning Analysis.

BACKGROUND: The role of the lipidome as a biomarker for Parkinson's disease (PD) is a relatively new field that currently only focuses on PD diagnosis. OBJECTIVE: To identify a relevant lipidome signature for PD severity markers. METHODS: Disease severity of 149 PD patients was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and the Montreal Cognitive Assessment (MoCA). The lipid composition of whole blood samples was analyzed, consisting of 517 lipid species from 37 classes; these included all major classes of glycerophospholipids, sphingolipids, glycerolipids, and sterols. To handle the high number of lipids, the selection of lipid species and classes was consolidated via analysis of interrelations between lipidomics and disease severity prediction using the random forest machine-learning algorithm aided by conventional statistical methods. RESULTS: Specific lipid classes dihydrosphingomyelin (dhSM), plasmalogen phosphatidylethanolamine (PEp), glucosylceramide (GlcCer), dihydro globotriaosylceramide (dhGB3), and to a lesser degree dihydro GM3 ganglioside (dhGM3), as well as species dhSM(20:0), PEp(38:6), PEp(42:7), GlcCer(16:0), GlcCer(24:1), dhGM3(22:0), dhGM3(16:0), and dhGB3(16:0) contribute to PD severity prediction of UPDRS III score. These, together with age, age at onset, and disease duration, also contribute to prediction of UPDRS total score. We demonstrate that certain lipid classes and species interrelate differently with the degree of severity of motor symptoms between men and women, and that predicting intermediate disease stages is more accurate than predicting less or more severe stages. CONCLUSION: Using machine-learning algorithms and methodologies, we identified lipid signatures that enable prediction of motor severity in PD. Future studies should focus on identifying the biological mechanisms linking GlcCer, dhGB3, dhSM, and PEp with PD severity.

The impact of COVID-19 and social distancing on people with Parkinson's disease: a survey study.

As the COVID-19 pandemic continues to affect the international community, very little is known about its impact on the health and day-to-day activities of people with Parkinson's disease (PwPD). To better understand the emotional and behavioral consequences of the public health policies implemented to mitigate the spread of SARS-CoV-2 in PwPD, and to explore the factors contributing to accessing alternative health care mechanisms, such as telehealth, we administered an anonymous knowledge, attitude, and practice survey to PwPD and care partners, via the mailing lists of the Parkinson's Foundation and Columbia University Parkinson's Disease Center of Excellence with an average response rate of 19.3%. Sufficient information was provided by 1,342 PwPD to be included in the final analysis. Approximately half of respondents reported a negative change in PD symptoms, with 45-66% reporting mood disturbances. Telehealth use increased from 9.7% prior to the pandemic to 63.5% during the pandemic. Higher income and higher education were associated with telehealth use. Services were more often used for doctor's appointment than physical, occupational, speech, or mental health therapies. Almost half (46%) of PwPD preferred to continue using telehealth always or sometimes after the coronavirus outbreak had ended. Having received support/instruction for telehealth and having a care partner, friend, or family member to help them with the telehealth visit increased the likelihood of continuous use of telehealth after the pandemic ended. Taken together, PD symptoms and management practices were markedly affected by COVID-19. Given the observed demographic limitations of telehealth, expanding its implementation to include additional physical, occupational, psychological, and speech therapies, increasing support for telehealth, as well as reaching underserved (low income) populations is urgently required.

Non-invasive Potential Circulating mRNA Markers for Colorectal Adenoma Using Targeted Sequencing.

We have developed an optimized protocol for plasma targeted mRNA sequencing in our previous study. Here, we performed plasma targeted mRNA sequencing for 40 colorectal adenoma patients and 39 colonoscopy-proven normal controls in order to find potential circulating mRNA markers for colorectal adenoma. Results showed that GSK3A and RHOA were differential expressed genes identified by a cut-off of fold change >2 and adjusted P value < 0.05. More detailed analysis showed that the expression of both GSK3A (0.01-fold with adjusted P < 1 × 10-6) and RHOA (0.35-fold with adjusted P < 0.01) in adenoma patients was significantly lower than those in normal healthy subjects. Based on the enrichment analysis of biological process for potential markers, we found that the regulation of programmed cell death (GO: 0043067; GO: 0043069), regulation of cell death (GO: 0010941; GO: 0060548) and cell differentiation (GO: 0021861) were the main processes involved in adenoma formation. In summary, this study is a cutting-edge research on the detection of plasma mRNA in colorectal adenoma patients and normal healthy subjects.

Distribution of human papillomavirus types in cervical cancers in Hong Kong: current situation and changes over the last decades.

Human papillomavirus (HPV) type distribution among cervical cancers and its possible changes over time are key issues that determine the cost-effectiveness of HPV vaccines. Cervical cancers diagnosed during 3 periods (1997-2007, N = 280; 1984-1986, N = 74; 1972-1973, N = 81) in Hong Kong were examined for HPV type distribution using sensitive broad-catching methods. The results showed a variation in HPV distribution between histological groups. Among cervical squamous cell carcinoma (SCC) cases diagnosed over the past 10 years, HPV16 was most commonly found (61.2%), followed by HPV18 (17.7%), HPV52 (14.7%) and HPV58 (9.9%), whereas adeno/adenosquamous cell carcinoma was dominated by HPV18 (56.3%) and HPV16 (50.0%). The proportion of HPV16-positive SCC showed a significant linear trend of increase with time (45.2% for 1972-1973, 58.8% for 1984-1986, 61.2% for 1997-2007; p(Trend) = 0.023), whereas HPV52-positive SCC decreased with time (30.1% for 1972-1973; 29.4% for 1984-1986, 14.7% for 1997-2007; p(Trend) = 0.001). Vaccines comprising HPV16/18 cover 62.6% of SCC and 93.8% of adeno/adenosquamous carcinoma in Hong Kong, and inclusion of HPV52 and HPV58 can increase the coverage by 18.4% for SCC and 4.1% for adeno/adenosquamous cell carcinoma. HPV type distribution may change over time. Further investigations to reveal the determinants for such changes and continuous monitoring for possible type replacement as a result of widespread long-term use of HPV vaccines are warranted. Multiple infections are commonly revealed by sensitive broad-catching methods such as those used in this study. However, their implication on vaccine efficacy and cost-effective analyses should be taken cautiously.

The contribution of bifunctional SkipDewax pretreatment solution, rabbit monoclonal antibodies, and polymer detection systems in immunohistochemistry.

CONTEXT: In immunohistochemistry, nonstandardized antigen retrieval protocols and fluids, poor-quality antibodies, and the presence of endogenous biotin frequently lead to incorrect results. Recently, advanced reagents including bifunctional SkipDewax pretreatment solution (BSPS), rabbit monoclonal (RM) antibodies, and biotin-free polymer detection systems (PDSs) have been developed, which, it is claimed, resolve these problems. OBJECTIVES: To determine whether BSPS, RM antibodies, and biotin-free PDSs improve the accuracy of immunohistochemistry; to optimize a new protocol consisting of a combination of BSPS, RM antibodies, and PDSs; and to compare it with a conventional protocol. DESIGN: The efficacies of BSPS, RM antibodies, and PDSs were compared with those of their respective conventional reagents using multitissue spring-roll sections. The new protocol was compared with a conventional protocol using Ki-67 immunostaining of 49 colorectal carcinoma specimens. RESULTS: For antigen retrieval, BSPS resulted in similar or better tissue staining than an EDTA solution, but the efficacy of BSPS decreased when it was reused. Most RM antibodies resulted in a greater proportion of positive cells than the corresponding non-RM antibodies, which did not produce satisfactory results in the absence of antigen retrieval. The PDSs Bond, ChemMate, and SuperPicture resulted in a high percentage of positive cells, good staining intensities, and low backgrounds. Other PDSs, except that from Ventana, resulted in high backgrounds and false positivity. The new combined protocol resulted in better Ki-67 staining than the conventional assay. CONCLUSIONS: Bifunctional SkipDewax pretreatment solution, RM antibodies, and PDSs improve staining quality and diagnostic accuracy of immunohistochemistry assays and provide a foundation for standardization.

Atypical epithelial proliferations in acquired renal cystic disease harbor cytogenetic aberrations.

Acquired renal cystic disease (ARCD) complicating end-stage renal failure confers an increased risk for renal cell carcinoma, and atypical epithelial proliferation in the cysts may represent the precursor lesion. In this report we used an interphase cytogenetic technique to analyze the karyotypic features of various forms of atypical epithelial proliferations in a patient with ARCD. Both kidneys harbored numerous simple and atypical cysts. In addition, papillary tufts and a hitherto undescribed cribriform epithelial proliferation were found in the right kidney. The left kidney contained a 10-mm renal cell carcinoma with features indeterminate between clear cell and papillary types. There was gain of chromosome 7 in the papillary tufts; gain of chromosomes 7 and 17 in the cribriform lesion; gain of chromosomes 7, 12, 17, 20, and Y in the atypical cysts; and gain of chromosomes 7, 12, 17, and 20 in the renal cell carcinoma. These chromosomal aberrations suggest that atypical epithelial proliferations in ARCD represent early neoplastic lesions.