O-linked N-acetylglucosamine transferase (OGT) reversibly modifies serine and threonine residues of many intracellular proteins with a single ␤-O-linked N-acetylglucosamine residue (O-GlcNAc), and has been implicated in insulin signaling, neurodegenerative disease, cellular stress response, and other important processes in mammals. OGT also glycosylates RNA polymerase II and various transcription factors, which suggests that it might be directly involved in transcriptional regulation. We report here that the Drosophila OGT is encoded by the Polycomb group (PcG) gene, super sex combs (sxc). Furthermore, major sites of O-GlcNAc modification on polytene chromosomes correspond to PcG protein binding sites. Our results thus suggest a direct role for O-linked glycosylation by OGT in PcG-mediated epigenetic gene silencing, which is important in developmental regulation, stem cell maintenance, genomic imprinting, and cancer. In addition, we observe rescue of sxc lethality by a human Ogt cDNA transgene; thus Drosophila may provide an ideal model to study important functional roles of OGT in mammals.epigenetic ͉ gene silencing ͉ O-glycosylation ͉ glycosyl transferase

Background Successful patient-physician communication is critical for improving health outcomes, but research regarding optimal communication practices in Parkinson’s disease is limited. The objective of the current study was to investigate barriers and facilitators of communication between persons with Parkinson’s disease, carepartners, and physicians, specifically in the setting of off periods, with the goal of identifying ways to improve patient-carepartner-physician communication. Method We interviewed persons with Parkinson’s, carepartners, and physicians (specialists and non-specialists) using a semi-structured questionnaire to identify and describe experiences, barriers, and facilitators relating to communication about off periods in Parkinson’s disease. We used a qualitative descriptive approach to analyze interview transcripts and compare themes between participating groups. Results Twenty persons with Parkinson’s and their carepartners and 20 physicians (10 specialists, 10 non-specialists) participated in interviews. Identified communication barriers included patient-level (e.g. cognitive impairment, reluctance to discuss symptoms), caregiver-level (e.g. caregiver absence), and physician-level (e.g. distraction by technology, lack of appreciation of the burden of off periods) factors. Other barriers included the challenging nature of off periods themselves. Positive physician characteristics such as empathy, respect, and taking time to listen were major facilitators of communication regarding off periods. Persons with Parkinson’s, carepartners, and physicians described using various tools (e.g. home diaries, questionnaires, mobile phone videos) to aid communication regarding off periods but participants identified a need for more formal educational materials. Conclusions Physicians caring for persons with Parkinson’s can improve communication through more patient-centered practice but there is a need for improved educational tools regarding off periods. Further research is needed to identify optimal strategies for communication about off periods and preferred approaches for off period education.

Objective This study explored how care partners (CPs) of persons with Parkinson's (PwP) are engaged in discussions of “off” symptoms. Methods During qualitative interviews, CPs of PwP sampled by convenience through the Michael J Fox Foundation online clinical trial matching service were asked to describe their familiarity with “off” symptoms, how “off” symptoms were discussed with clinicians, and the impact of “off” symptoms on them. Data were analysed using constant comparative technique by all members of the research team. Results A total of 20 CPs were interviewed. Compared with PwP, they were more likely to describe “off” symptoms to clinicians. CPs identified important aspects of patient‐centred care for PD: establishing a therapeutic relationship, soliciting and actively listening to information about symptoms, and providing self‐management support to both PwP and CPs. CPs said that clinicians did not always engage CPs, ask about “off” symptoms or provide self‐management guidance, limiting their ability to function as caregivers. Conclusion By not engaging and educating CPs, “off” symptoms may not be identified or addressed, leading to suboptimal medical management and quality of life for PwP. These findings must be confirmed on a broader scale through ongoing research but suggest the potential need for interventions targeted at clinicians and at CPs to promote patient‐centred care for PwP.

Background Off periods are a common and disabling symptom of Parkinson's disease. We reviewed published research on understanding, impact, and communication regarding off periods to identify issues warranting further research. Methods We performed a scoping review, searching MEDLINE, EMBASE, Cochrane Library, CINAHL, and PsycINFO from 2006 to January 2018 for studies examining the impact of, understanding of, or communication about off periods. Results Twenty‐six papers met eligibility criteria. Twenty‐three studies evaluated the impact or experience of off periods in patients, three evaluated the impact upon carepartners, two papers addressed understanding of off periods, one study evaluated communication about off periods, and three studies evaluated a facilitator of communication about off periods. The findings indicate that (1) off periods are among the most troublesome symptoms to patients and that their impact on activities is broad; (2) the understanding of off periods by patients, carepartners, and nurses may be suboptimal; and (3) questionnaires hold promise as a mechanism for facilitating communication given the findings that they may enhance the detection of off periods and are rated as useful by physicians. No studies evaluated interventions to promote knowledge about off periods, and no studies identified barriers of communication about off periods. Conclusions There is a paucity of knowledge regarding the lived experiences of off periods, particularly for carepartners. Additionally, little knowledge exists in the literature regarding understanding of and communication about off periods between patients or carepartners and treating physicians. Further research is required to explore these issues to ultimately improve the treatment of off periods.

Background: OFF periods impair quality of life in Parkinson's disease and are often amenable to treatment. Optimal treatment decisions rely on effective communication between physicians, patients and carepartners regarding this highly variable and complex phenomenon. Little is published in the literature about communication about OFF periods. Methods: Informed by interviews with physicians, patients and carepartners we designed questionnaires for each group. We surveyed these parties using an online platform to investigate the frequency, content and ease of communication about OFF periods and barriers and facilitators of communication with physicians. Results: Fifty movement disorder neurologists, 50 general neurologists, 442 patients and 97 carepartners participated. A free-flowing dialogue is the mainstay of communication according to all parties. Motor aspects of OFF periods are discussed more frequently than non-motor aspects (90 vs. <50% according to both general neurologists and movement disorder neurologists). The most common physician-reported barriers to communication are patient cognitive impairment, patient difficulty recognizing OFF periods and poor patient understanding of OFF periods' relationship to medication timing. The barriers most commonly cited as major by patients were that they perceived OFF periods to be part of the disease (i.e., not a clinical aspect that could be improved by a physician), variability of symptoms, and difficulty in describing symptoms. The most commonly described facilitator (by physicians) was the input of a caregiver. Positively viewed but less commonly used facilitators included pre-visit questionnaires or diaries, digital apps and wearable devices to monitor fluctuations. The majority of patients and carepartners identified a free-flowing dialogue with their physicians and having an agenda as helpful facilitators of communication about OFF periods which they already use. The majority of both groups felt that keeping a diary and pre-visit questionnaires were potentially helpful facilitators that were not currently in use. Conclusions: Perceived barriers and facilitators to communication about OFF periods are different between health care providers and receivers of health care. Modifiable barriers and facilitators that could be implemented were identified by both groups. Future research should develop and test strategies based on this input to optimize communication and thus clinical care for this common and debilitating problem.

The historical context in which saccades are made influences their latency and error rates, but less is known about how context influences their spatial parameters. We recently described a novel spatial bias for antisaccades, in which the endpoints of these responses deviate towards alternative goal locations used in the same experimental block, and showed that expectancy (prior probability) is at least partly responsible for this 'alternategoal bias'. In this report we asked whether trial history also plays a role. Subjects performed antisaccades to a stimulus randomly located on the horizontal meridian, on a 40°a ngle downwards from the horizontal meridian, or on a 40°u pward angle, with all three locations equally probable on any given trial. We found that the endpoints of antisaccades were significantly displaced towards the goal location of not only the immediately preceding trial (n -1) but also the penultimate (n -2) trial. Furthermore, this bias was mainly present for antisaccades with a short latency of \250 ms and was rapidly corrected by secondary saccades. We conclude that the location of recent antisaccades biases the spatial programming of upcoming antisaccades, that this historical effect persists over many seconds, and that it influences mainly rapidly generated eye movements. Because corrective saccades eliminate the historical bias, we suggest that the bias arises in processes generating the response vector, rather than processes generating the perceptual estimate of goal location.

Introduction Off period research in Parkinson's disease commonly relies on questionnaires. We aimed to investigate the breadth of off period experiences by interviewing persons with Parkinson's disease (PwP) and carepartners. Methods Investigators performed PwP and carepartner dyad interviews using a semi-structured questionnaire to describe off period experiences. Investigators analyzed interview transcripts using a qualitative descriptive approach to identify and compare themes between groups. Results Twenty PwP and their carepartners participated in interviews. PwP were on average 65.1 years-old (SD 8.3) and 7.8 years (SD 4.7) after their Parkinson's disease diagnosis. PwP and carepartners identified 13 motor symptoms, 5 of which (immobility, gait changes, freezing, trouble swallowing, and having to concentrate on movements) were not in the wearing off questionnaires recommended by the International Parkinson and Movement Disorders Society. PwP and carepartners identified 15 non-motor symptoms, 8 of which (behavior changes, irritability, fatigue, language difficulties, dizziness, dry mouth, urinary symptoms, and swollen feet) were not in recommended questionnaires. Certain symptoms were reported only by PwP (e.g. dizziness, urinary symptoms) or carepartners (e.g. behavioral changes), or were reported by dyad members to different degrees (e.g. fatigue, anxiety). Conclusion Wearing off questionnaires capture the presence of fluctuations and can facilitate patient-physician communication regarding off periods. However, they may miss the breadth of individual PwP experiences. PwP and carepartners also report different PwP experiences during off periods. To fully appreciate an individual's off experiences, clinicians likely need to use multiple approaches to gathering information including questionnaires and both PwP and carepartner report.

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