Statins are underused in recent-onset Parkinson's disease with increased vascular risk : findings from the UK Tracking Parkinson's and Oxford Parkinson's Disease Centre (OPDC) discovery cohorts

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Differential effects of tactile high- and low-frequency stimulation on tactile discrimination in human subjects

<p>Abstract</p> <p>Background</p> <p>Long-term potentiation (LTP) and long-term depression (LTD) play important roles in mediating activity-dependent changes in synaptic transmission and are believed to be crucial mechanisms underlying learning and cortical plasticity. In human subjects, however, the lack of adequate input stimuli for the induction of LTP and LTD makes it difficult to study directly the impact of such protocols on behavior.</p> <p>Results</p> <p>Using tactile high- and low-frequency stimulation protocols in humans, we explored the potential of such protocols for the induction of perceptual changes. We delivered tactile high-frequency and low-frequency stimuli (t-HFS, t-LFS) to skin sites of approximately 50 mm²on the tip of the index finger. As assessed by 2-point discrimination, we demonstrate that 20 minutes of t-HFS improved tactile discrimination, while t-LFS impaired performance. T-HFS-effects were stable for at least 24 hours whereas t-LFS-induced changes recovered faster. While t-HFS changes were spatially very specific with no changes on the neighboring fingers, impaired tactile performance after t-LFS was also observed on the right middle-finger. A central finding was that for both t-LFS and t-HFS perceptual changes were dependent on the size of the stimulated skin area. No changes were observed when the stimulated area was very small (< 1 mm²) indicating special requirements for spatial summation.</p> <p>Conclusion</p> <p>Our results demonstrate differential effects of such protocols in a frequency specific manner that might be related to LTP- and LTD-like changes in human subjects.</p

Prostate Cancer Foundation Hormone-Sensitive Prostate Cancer Biomarker Working Group Meeting Summary.

Androgen deprivation therapy remains the backbone therapy for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). In recent years, several treatments, including docetaxel, abiraterone + prednisone, enzalutamide, and apalutamide, have each been shown to demonstrate survival benefit when used upfront along with androgen deprivation therapy. However, treatment selection for an individual patient remains a challenge. There is no high level clinical evidence for treatment selection among these choices based on biological drivers of clinical disease. In August 2020, the Prostate Cancer Foundation convened a working group to meet and discuss biomarkers for hormone-sensitive prostate cancer, the proceedings of which are summarized here. This meeting covered the state of clinical and biological evidence for systemic therapies in the mHSPC space, with emphasis on charting a course for the generation, interrogation, and clinical implementation of biomarkers for treatment selection

A typology of loss and damage perspectives

Loss and Damage (L&D) has been the subject of contentious debate in international climate policy for several decades. Recently, formal mechanisms on L&D have been established, but arguably through unclear language. This ambiguity is politically important, but researchers and practitioners require clearer understandings of L&D. Here we report on the first in-depth empirical study of actor perspectives, including interviews with 38 key stakeholders in research, practice, and policy. We find points of agreement and also important distinctions in terms of: the relationship between L&D and adaptation, the emphasis on avoiding versus addressing L&D, the relevance of anthropogenic climate change, and the role of justice. A typology of four perspectives is identified, with different implications for research priorities and actions to address L&D. This typology enables improved understanding of existing perspectives and so has potential to facilitate more transparent discussion of the options available to address L&D

A Self-Reference False Memory Effect in the DRM Paradigm: Evidence from Eastern and Western Samples

It is well established that processing information in relation to oneself (i.e., selfreferencing) leads to better memory for that information than processing that same information in relation to others (i.e., other-referencing). However, it is unknown whether self-referencing also leads to more false memories than other-referencing. In the current two experiments with European and East Asian samples, we presented participants the Deese-Roediger/McDermott (DRM) lists together with their own name or other people’s name (i.e., “Trump” in Experiment 1 and “Li Ming” in Experiment 2). We found consistent results across the two experiments; that is, in the self-reference condition, participants had higher true and false memory rates compared to those in the other-reference condition. Moreover, we found that selfreferencing did not exhibit superior mnemonic advantage in terms of net accuracy compared to other-referencing and neutral conditions. These findings are discussed in terms of theoretical frameworks such as spreading activation theories and the fuzzytrace theory. We propose that our results reflect the adaptive nature of memory in the sense that cognitive processes that increase mnemonic efficiency may also increase susceptibility to associative false memories

Statins are underused in recent-onset Parkinson's disease with increased vascular risk: findings from the UK Tracking Parkinson's and Oxford Parkinson's Disease Centre (OPDC) discovery cohorts.

BACKGROUND: Cardiovascular disease (CVD) influences phenotypic variation in Parkinson's disease (PD), and is usually an indication for statin therapy. It is less clear whether cardiovascular risk factors influence PD phenotype, and if statins are prescribed appropriately. OBJECTIVES: To quantify vascular risk and statin use in recent-onset PD, and examine the relationship between vascular risk, PD severity and phenotype. METHODS: Cardiovascular risk was quantified using the QRISK2 calculator (high ≥20%, medium ≥10 and <20%, low risk <10%). Motor severity and phenotype were assessed using the Movement Disorder Society Unified PD Rating Scale (UPDRS) and cognition by the Montreal cognitive assessment. RESULTS: In 2909 individuals with recent-onset PD, the mean age was 67.5 years (SD 9.3), 63.5% were men and the mean disease duration was 1.3 years (SD 0.9). 33.8% of cases had high vascular risk, 28.7% medium risk, and 22.3% low risk, while 15.2% of cases had established CVD. Increasing vascular risk and CVD were associated with older age (p<0.001), worse motor score (p<0.001), more cognitive impairment (p<0.001) and worse motor phenotype (p=0.021). Statins were prescribed in 37.2% with high vascular risk, 15.1% with medium vascular risk and 6.5% with low vascular risk, which compared with statin usage in 75.3% of those with CVD. CONCLUSIONS: Over 60% of recent-onset PD patients have high or medium cardiovascular risk (meriting statin usage), which is associated with a worse motor and cognitive phenotype. Statins are underused in these patients, compared with those with vascular disease, which is a missed opportunity for preventive treatment. TRIAL REGISTRATION NUMBER: GN11NE062, NCT02881099

Visual function improvement using photocromic and selective blue-violet light filtering spectacle lenses in patients affected by retinal diseases

Background To evaluate functional visual parameters using photocromic and selective blue-violet light filtering spectacle lenses in patients affected by central or peripheral scotoma due to retinal diseases. Sixty patients were enrolled in this study: 30 patients affected by central scotoma, group 1, and 30 affected by peripheral scotoma, group 2. Black on White Best Corrected Visual Acuity (BW-BCVA), White on Black Best Corrected Visual Acuity (WB-BCVA), Mars Contrast Sensitivity (CS) and a Glare Test (GT) were performed to all patients. Test results with blue-violet filter, a short-pass yellow filter and with no filters were compared. Results All scores from test results increased significantly with blue-violet filters for all patients. The mean BW-BCVA increased from 0.30 ± 0.20 to 0.36 ± 0.21 decimals in group 1 and from 0.44 ± 0.22 to 0.51 ± 0.23 decimals in group 2 (Mean ± SD, p < 0.0001 in both cases). The mean WB-BCVA increased from 0.31 ± 0.19 to 0.38 ± 0.23 decimals in group 1 and from 0.46 ± 0.20 to 0.56 ± 0.22 decimals in group 2 (Mean ± SD, p < 0.0001 in both cases). The letter count for the CS test increased from 26.7 ± 7.9 to 30.06 ± 7.8 in group 1 (Mean ± SD, p = 0.0005) and from 31.5 ± 7.6 to 33.72 ± 7.3 in group 2 (Mean ± SD, p = 0.031). GT was significantly reduced: the letter count increased from 20.93 ± 5.42 to 22.82 ± 4.93 in group 1 (Mean ± SD, p < 0.0001) and from 24.15 ± 5.5 to 25.97 ± 4.7 in group 2 (Mean ± SD, p < 0.0001). Higher scores were recorded with the Blue filter compared to Yellow filter in all tests (p < 0.05). No significant differences in any test results could be detected between the Yellow filter and the No filter condition. Conclusions The use of a combination of photocromic lens with a selective blue-violet light filter showed functional benefit in all evaluated patients

Using functional genomics to decipher the complexity of microbial pathogenicity

From the first identification of bacteria as a causative agent of disease, researchers have been developing methods and techniques to understand their pathogenic processes. For decades, this work has been limited to looking at a small number of genetically manipulatable isolates in in vitro assays or animal models of infection. Despite these limitations such work has facilitated the development of successful therapeutic strategies, most notably vaccines that target specific virulence-related features. There are however many antimicrobial resistant pathogens for which vaccination strategies have not worked, as we simply do not know enough about how they cause disease. We are however at the dawn of a new era in the study of microbial pathogenicity, where large collections of bacteria isolated directly from human infections can be sequenced and assayed to identify the bacterial features that affect disease severity in humans. Here, we describe our attempt to perform such a study focussed on the major human pathogen Staphylococcus aureus, which demonstrates the step changes such approaches can make to understanding microbial pathogenicity

Dysregulation in Retinal Para-Inflammation and Age-Related Retinal Degeneration in CCL2 or CCR2 Deficient Mice

We have shown previously that a para-inflammatory response exists at the retinal/choroidal interface in the aging eye; and this response plays an important role in maintaining retinal homeostasis under chronic stress conditions. We hypothesized that dysregulation of the para-inflammatory response may result in an overt pro-inflammatory response inducing retinal degeneration. In this study, we examined this hypothesis in mice deficient in chemokine CCL2 or its cognate receptor CCR2. CCL2- or CCR2-deficient mice developed retinal degenerative changes with age, characterized as retinal pigment epithelial (RPE) cell and photoreceptor cell death. Retinal cell death was associated with significantly more subretinal microglial accumulation and increased complement activation. In addition, monocytes from CCL2- or CCR2-deficient mice had reduced capacity for phagocytosis and chemotaxis, expressed less IL-10 but more iNOS, IL-12 and TNF-α when compared to monocytes from WT mice. Complement activation at the site of RPE cell death resulted in C3b/C3d but not C5b-9 deposition, indicating only partial activation of the complement pathway. Our results suggest that altered monocyte functions may convert the protective para-inflammatory response into an overtly harmful inflammation at the retina/choroidal interface in CCL2- or CCR2-deficient mice, leading to RPE and photoreceptor degeneration. These data support a concept whereby a protective para-inflammatory response relies upon a normally functioning innate immune system. If the innate immune system is deficient chronic stress may tip the balance towards an overt inflammatory response causing cell/tissue damage

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

National Coordinating Centre for Research Methodology; Medical Research Council, UK Department of Health; Chief Scientist OfficeNot peer reviewedPublisher PD