IGLON5 Frequency in Idiopathic REM Sleep Behavior Disorder: A Multicenter Study.

BACKGROUND AND OBJECTIVES: Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD. METHODS: Participants were enrolled in the North American Prodromal Synucleinopathy cohort with polysomnography-confirmed iRBD, free of parkinsonism and dementia. Plasma samples were systematically screened for the autoantibodies IGLON5, DPPX, LGI1, and CASPR2 using plasma IgG cell-based assay. Positive or equivocal results were confirmed by repeat testing, plus tissue-based indirect immunofluorescence assay for IGLON5. RESULTS: Of 339 samples analyzed, 3 participants (0.9%) had confirmed positive IGLON5 autoantibodies in the cell-based assay, which were confirmed by the tissue-based assay. An additional participant was positive for CASPR2 with low titer by cell-based assay only (of lower clinical certainty). These cases exhibited a variety of symptoms including dream enactment, cognitive decline, autonomic dysfunction, and motor symptoms. In 1 IGLON5 case and the CASPR2 case, evolution was suggestive of typical synucleinopathy, suggesting the possibility that findings were incidental. However, 2 participants with IGLON5 died before diagnosis was clinically suspected, with a final clinical picture highly suggestive of autoimmune disease. DISCUSSION: Our finding that nearly 1% of a large iRBD cohort may have a serious but potentially treatable autoantibody syndrome has important clinical implications. In particular, it raises the question of whether autoantibody testing for IGLON-5-IgG should be widely implemented for participants with iRBD, considering the difficulty in diagnosis of autoimmune diseases, their response to treatment, and the potential for rapid disease progression. However, any routine testing protocol will also have to consider costs and potential adverse effects of false-positive findings. TRIAL REGISTRATION INFORMATION: NCT03623672.

Clinical characteristics and phenoconversion in isolated REM sleep behavior disorder: a prospective single-center study in Korea, compared with Montreal cohort.

STUDY OBJECTIVES: Isolated rapid-eye movement behavior disorder (iRBD) is a prodromal synucleinopathy, but its conversion rate and subtypes can vary among different cohorts. We report the clinical characteristics and phenoconversion rate of the large single-center iRBD cohort in Korea and compared it to the Montreal cohort. METHODS: This prospective cohort study examined 238 patients with polysomnography confirmed iRBD from Seoul National University Hospital (SNUH) who completed at least one follow-up evaluation. We compared the baseline and phenoconversion data of the SNUH cohort to those of 242 iRBD patients in the Montreal cohort. RESULTS: In the SNUH cohort, age at RBD diagnosis was similar (66.4±7.8 vs 65.6±8.4, p=0.265), but the proportion of men was lower (63.0% vs. 74.0%, p=0.001), and the duration of follow-up was shorter than that in the Montreal cohort (3.7±2.0 vs. 4.8±3.6 years, p<0.001). During follow-up, 34 (11.8%) patients in the SNUH cohort converted to neurodegenerative disease: 18 (52.9%) to Parkinson's disease, 9 (26.5%) to dementia with Lewy bodies (DLB), and 7 (20.6%) to multiple system atrophy. The conversion rate in the SNUH cohort was 15% after 3 years, 22% after 5 years, and 32% after 7 years, which was significantly lower than that of the Montreal cohort (log-rank test, p=0.002). Among phenoconversion subtype, fewer subjects in the SNUH group than in the Montreal group converted to DLB (Gray's test p=0.001). CONCLUSIONS: Through a comparative analysis between the SNUH and Montreal cohorts, we identified a significant difference in phenoconversion rates, particularly for DLB patients. These findings underscore the importance of further research into the underlying factors, such as racial and geographical factors contributing to such disparities.

Clinical symptoms and neuroanatomical substrates of daytime sleepiness in Parkinson's disease.

Clinical and neuroanatomical correlates of daytime sleepiness in Parkinson's disease (PD) remain inconsistent in the literature. Two studies were conducted here. The first evaluated the interrelation between non-motor and motor symptoms, using a principal component analysis, associated with daytime sleepiness in PD. The second identified the neuroanatomical substrates associated with daytime sleepiness in PD using magnetic resonance imaging (MRI). In the first study, 77 participants with PD completed an extensive clinical, cognitive testing and a polysomnographic recording. In the second study, 29 PD participants also underwent MRI acquisition of T1-weighted images. Vertex-based cortical and subcortical surface analysis, deformation-based morphometry, and voxel-based morphometry were performed to assess the association between daytime sleepiness severity and structural brain changes in participants. In both studies, the severity of daytime sleepiness and the presence of excessive daytime sleepiness (EDS; total score >10) were measured using the Epworth Sleepiness Scale. We found that individuals with EDS had a higher score on a component including higher dosage of dopamine receptor agonists, motor symptoms severity, shorter sleep latency, and greater sleep efficiency. Moreover, increased daytime sleepiness severity was associated with a larger surface area in the right insula, contracted surfaces in the right putamen and right lateral amygdala, and a larger surface in the right posterior amygdala. Hence, daytime sleepiness in PD was associated with dopaminergic receptor agonists dosage, motor impairment, and objective sleep measures. Moreover, neuroanatomical changes in cortical and subcortical regions related to vigilance, motor, and emotional states were associated with more severe daytime sleepiness.

The influence of social knowledge structures on hostile attribution bias in aggressive and nonaggressive individuals: An ERP study.

According to several social-cognitive models, social knowledge structures described as hostile scripts or schemas may explain why aggressive individuals are prone to attribute hostile intention to others' ambiguous behaviors, a cognitive bias called hostile attribution bias (HAB). The aggression-related concepts in aggressive individuals' semantic memory would be highly accessible, notably through the activation of hostile concepts in nonhostile social contexts, and such an activation would result in HAB. The aim of the study was to test this hypothesis using the N400 component with EEG measurements to assess objectively, in real time, the violation of hostile expectations following a nonhostile situation. To this end, scenarios with a clear nonhostile context (mismatch condition) vs. without nonhostile context (match condition) followed by a character's ambiguous provocative behavior were presented to readers, and ERPs to critical words that specified the hostile intent behind the behavior were analysed. Twelve aggressive and twelve nonaggressive individuals participated in the study. The presentation of a critical word (hostile intent) that violated nonhostile expectation caused an N400 response among nonaggressive whereas such an N400 effect was absent in aggressive individuals. The results suggest that, in nonaggressive individuals, a nonhostile social context activates nonhostile concepts, whereas in the same context, aggressive individuals activate nonhostile as well as hostile concepts. Numerous research applications of the Hostile Expectancy Violation paradigm in the field of HAB are discussed.

Longitudinal Network Changes and Phenoconversion Risk in Isolated REM Sleep Behavior Disorder.

Isolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal syndrome for Parkinson's disease (PD) and related α-synucleinopathies. We conducted a longitudinal imaging study of network changes in iRBD and their relationship to phenoconversion. Expression levels for the PD-related motor and cognitive networks (PDRP and PDCP) were measured at baseline, 2 and 4 years, along with dopamine transporter (DAT) binding. PDRP and PDCP expression increased over time, with higher values in the former network. While abnormal functional connections were identified initially within the PDRP, others bridging the two networks appeared later. A model based on the rates of PDRP progression and putamen dopamine loss predicted phenoconversion within 1.2 years in individuals with iRBD. In aggregate, the data suggest that maladaptive reorganization of brain networks takes place in iRBD years before phenoconversion. Network expression and DAT binding measures can be used together to assess phenoconversion risk in these individuals.

Quantifying flare combustion efficiency using an imaging Fourier transform spectrometer.

Mid-wavelength infrared (MWIR) imaging Fourier transform spectrometers (IFTSs) are a promising technology for measuring flare combustion efficiency (CE) and destruction removal efficiency (DRE). These devices generate spectrally resolved intensity images of the flare plume, which may then be used to infer column densities of relevant species along each pixel line-of-sight. In parallel, a 2D projected velocity field may be inferred from the apparent motion of flow features between successive images. Finally, the column densities and velocity field are combined to estimate the mass flow rates for the species needed to calculate the CE or DRE. Since the MWIR IFTS can measure key carbon-containing species in the flare plume, it is possible to measure CE without knowing the fuel flow rate, which is important for fenceline measurements. This work demonstrates this approach on a laboratory heated vent, and then deploys the technique on two working flares: a combustor burning natural gas at a known rate, and a steam-assisted flare at a petrochemical refinery. Analysis of the IFTS data highlights the potential of this approach, but also areas for future development to transform this approach into a reliable technique for quantifying flare emissions.Implications: Our research is motivated by the need to assess hydrocarbon emissions from flaring, which is a critical problem of global significance. For example, recent studies have shown that methane destruction efficiency of flaring from upstream oil may be significantly lower than the commonly assumed figure of 98%; work by Plant et al. , in particular, suggest that this discrepancy amounts to CO2 emissions from 2 to 8 million automobiles annually, considering the US alone. Similarly, the international energy agency (IEA) estimates a global flare efficiency of 92%, which translates in 8 million tons of CH4 emitted by flares in 2020. Highlighted by these studies and supported by the World Bank initiatives toward zero routine flaring emissions, there is an urgent need for oil and gas industry to assess their flare methane emission, and overall hydrocarbon emissions. At the very least, it is critical to identify problematic flare operating conditions and means to mitigate flare emissions. Focusing on remote quantification of plume species, the measurement technique and quantification method presented in this paper is a considerable step forward in that direction by computing combustion efficiency and key components for destruction efficiency.

99mTc-HMPAO SPECT Perfusion Signatures Associated With Clinical Progression in Patients With Isolated REM Sleep Behavior Disorder.

BACKGROUND AND OBJECTIVES: Idiopathic/isolated REM sleep behavior disorder (iRBD) is associated with dementia with Lewy bodies and Parkinson disease. Despite evidence of abnormal cerebral perfusion in iRBD, there is currently no pattern that can predict whether an individual will develop dementia with Lewy bodies or Parkinson disease. The objective was to identify a perfusion signature associated with conversion to dementia with Lewy bodies in iRBD. METHODS: Patients with iRBD underwent video-polysomnography, neurologic and neuropsychological assessments, and baseline 99mTc-HMPAO SPECT to assess relative cerebral blood flow. Partial least squares correlation was used to identify latent variables that maximized covariance between 27 clinical features and relative gray matter perfusion. Patient-specific scores on the latent variables were used to test the association with conversion to dementia with Lewy bodies compared with that with Parkinson disease. The signature's expression was also assessed in 24 patients with iRBD who underwent a second perfusion scan, 22 healthy controls, and 19 individuals with Parkinson disease. RESULTS: Of the 137 participants, 93 underwent SPECT processing, namely 52 patients with iRBD (67.9 years, 73% men), 19 patients with Parkinson disease (67.3 years, 37% men), and 22 controls (67.0 years, 73% men). Of the 47 patients with iRBD followed up longitudinally (4.5 years), 12 (26%) developed a manifest synucleinopathy (4 dementia with Lewy bodies and 8 Parkinson disease). Analysis revealed 2 latent variables between relative blood flow and clinical features: the first was associated with a broad set of features that included motor, cognitive, and perceptual variables, age, and sex; the second was mostly associated with cognitive features and RBD duration. When brought back into the patient's space, the expression of the first variable was associated with conversion to a manifest synucleinopathy, whereas the second was associated with conversion to dementia with Lewy bodies. The expression of the patterns changed over time and was associated with worse motor features. DISCUSSION: This study identified a brain perfusion signature associated with cognitive impairment in iRBD and transition to dementia with Lewy bodies. This signature, which can be derived from individual scans, has the potential to be developed into a biomarker that predicts dementia with Lewy bodies in at-risk individuals.

Validation of the RBD Symptom Severity Scale in the North American Prodromal Synucleinopathy Consortium.

BACKGROUND AND OBJECTIVES: REM sleep behavior disorder (RBD) is a parasomnia characterized by dream enactment. The International RBD Study Group developed the RBD Symptom Severity Scale (RBDSSS) to assess symptom severity for clinical or research use. We assessed the psychometric and clinimetric properties of the RBDSSS in participants enrolled in the North American Prodromal Synucleinopathy (NAPS) Consortium for RBD. METHODS: NAPS participants, who have polysomnogram-confirmed RBD, and their bedpartners completed the RBDSSS (participant and bedpartner versions). The RBDSSS contains 8 questions to assess the frequency and severity/impact of (1) dream content, (2) vocalizations, (3) movements, and (4) injuries associated with RBD. Total scores for participant (maximum score = 54) and bedpartner (maximum score = 38) questionnaires were derived by multiplying frequency and severity scores for each question. The Clinical Global Impression Scale of Severity (CGI-S) and RBD symptom frequency were assessed by a physician during a semistructured clinical interview with participants and, if available, bedpartners. Descriptive analyses, correlations between overall scores, and subitems were assessed, and item response analysis was performed to determine the scale's validity. RESULTS: Among 261 study participants, the median (interquartile range) score for the RBDSSS-PT (participant) was 10 (4-18) and that for the RBDSSS-BP (bedpartner) was 8 (4-15). The median CGI-S was 3 (3-4), indicating moderate severity. RBDSSS-BP scores were significantly lower in women with RBD (6 vs 9, p = 0.02), while there were no sex differences in RBDSSS-PT scores (8 vs 10.5, p = 0.615). Positive correlations were found between RBDSSS-PT vs RBDSSS-BP (Spearman rs = 0.561), RBDSSS-PT vs CGI-S (rs = 0.556), and RBDSSS-BP vs CGI-S (rs = 0.491, all p < 0.0001). Item response analysis showed a high discriminatory value (range 1.40-2.12) for the RBDSSS-PT and RBDSSS-BP (1.29-3.47). DISCUSSION: We describe the RBDSSS with adequate psychometric and clinimetric properties to quantify RBD symptom severity and good concordance between participant and bedpartner questionnaires and between RBDSSS scores and clinician-assessed global severity.

Comorbid neurotrauma increases neurodegenerative-relevant cognitive, motor, and autonomic dysfunction in patients with rapid eye movement sleep behavior disorder: a substudy of the North American Prodromal Synucleinopathy Consortium.

STUDY OBJECTIVES: Rapid eye movement sleep behavior disorder (RBD) is strongly associated with phenoconversion to an overt synucleinopathy, e.g. Parkinson's disease (PD), Lewy body dementia, and related disorders. Comorbid traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD)-henceforth "neurotrauma" (NT)-increase the odds of RBD by ~2.5-fold and are associated with an increased rate of service-connected PD in Veterans. Thus, RBD and NT are both independently associated with PD; however, it is unclear how NT influences neurological function in patients with RBD. METHODS: Participants ≥18 years with overnight polysomnogram-confirmed RBD were enrolled between 8/2018 to 4/2021 through the North American Prodromal Synucleinopathy Consortium. Standardized assessments for RBD, TBI, and PTSD history, as well as cognitive, motor, sensory, and autonomic function, were completed. This cross-sectional analysis compared cases (n = 24; RBD + NT) to controls (n = 96; RBD), matched for age (~60 years), sex (15% female), and years of education (~15 years). RESULTS: RBD + NT reported earlier RBD symptom onset (37.5 ±â€…11.9 vs. 52.2 ±â€…15.1 years of age) and a more severe RBD phenotype. Similarly, RBD + NT reported more severe anxiety and depression, greater frequency of hypertension, and significantly worse cognitive, motor, and autonomic function compared to RBD. No differences in olfaction or color vision were observed. CONCLUSIONS: This cross-sectional, matched case:control study shows individuals with RBD + NT have significantly worse neurological measures related to common features of an overt synucleinopathy. Confirmatory longitudinal studies are ongoing; however, these results suggest RBD + NT may be associated with more advanced neurological symptoms related to an evolving neurodegenerative process.

Montreal Cognitive Assessment and the Clock Drawing Test to Identify MCI and Predict Dementia in Isolated REM Sleep Behavior Disorder.

BACKGROUND AND OBJECTIVES: Patients with isolated/idiopathic REM sleep behavior disorder (iRBD) are at high risk for developing mild cognitive impairment (MCI) and dementia with Lewy bodies (DLB). However, there is a lack of scientific knowledge regarding the accuracy of cognitive screening tools to identify these conditions in iRBD. This study aimed to determine in iRBD the psychometrics of 2 screening tests to discriminate patients with MCI and those at risk of DLB. METHODS: We retrospectively selected and followed 64 patients with polysomnography-confirmed iRBD seen in sleep clinic between 2006 and 2021, 32 with MCI (mean age 68.44 years, 72% men), 32 without MCI (67.78 years, 66% men), and 32 controls (69.84 years, 47% men). Participants underwent a neurologic evaluation and neuropsychological assessment for MCI diagnosis. They also completed the Montreal Cognitive Assessment (MoCA) and Clock Drawing Test (CDT). Fifty-three patients were followed (mean of 5.10 ± 2.64 years); 6 developed DLB, and 16 developed Parkinson disease. An independent cohort of 10 patients with iRBD who later developed DLB was also recruited and followed. Receiver operating characteristic curves with area under the curve (AUC) were performed assessing the discriminant value of the MoCA and CDT. RESULTS: The cut-off values that best differentiated patients who developed DLB from controls were on the MoCA total score (≤25/30 with 100% [95% CI 61%-100%] sensitivity and 78% [61%-89%] specificity, AUC = 0.888) and delayed recall (≤3/5 with 83% [44%-97%] sensitivity and 78% [61%-89%] specificity, AUC = 0.875). Both values yielded a sensitivity of 90% (60%-98%) to detect patients at risk of DLB in the independent cohort. Cutoffs that best discriminated patients with MCI from controls were: ≤25/30 (MoCA total score) with 72% [55%-84%] sensitivity, 78% [61%-89%] specificity, AUC = 0.803 and ≤2/5 (MoCA delayed recall) with 63% [45%-77%] sensitivity, 94% [80%-98%] specificity, AUC = 0.843. No acceptable optimal values were found for the CDT. DISCUSSION: In iRBD, the MoCA demonstrates adequate psychometric properties to identify patients most at risk of developing DLB and to screen for MCI, whereas the CDT does not. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the MoCA, but not the CDT, is useful in screening patients with iRBD for the risk of developing DLB.

Prodromal dementia with Lewy bodies in REM sleep behavior disorder: A multicenter study.

INTRODUCTION: Isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) is a powerful early predictor of dementia with Lewy bodies (DLB) and Parkinson's disease (PD). This provides an opportunity to directly observe the evolution of prodromal DLB and to identify which cognitive variables are the strongest predictors of evolving dementia. METHODS: IRBD participants (n = 754) from 10 centers of the International RBD Study Group underwent annual neuropsychological assessment. Competing risk regression analysis determined optimal predictors of dementia. Linear mixed-effect models determined the annual progression of neuropsychological testing. RESULTS: Reduced attention and executive function, particularly performance on the Trail Making Test Part B, were the strongest identifiers of early DLB. In phenoconverters, the onset of cognitive decline began up to 10 years prior to phenoconversion. Changes in verbal memory best differentiated between DLB and PD subtypes. DISCUSSION: In iRBD, attention and executive dysfunction strongly predict dementia and begin declining several years prior to phenoconversion. HIGHLIGHTS: Cognitive decline in iRBD begins up to 10 years prior to phenoconversion. Attention and executive dysfunction are the strongest predictors of dementia in iRBD. Decline in episodic memory best distinguished dementia-first from parkinsonism-first phenoconversion.

Spoken Language Alterations can Predict Phenoconversion in Isolated Rapid Eye Movement Sleep Behavior Disorder: A Multicenter Study.

OBJECTIVE: This study assessed the relationship between speech and language impairment and outcome in a multicenter cohort of isolated/idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). METHODS: Patients with iRBD from 7 centers speaking Czech, English, German, French, and Italian languages underwent a detailed speech assessment at baseline. Story-tale narratives were transcribed and linguistically annotated using fully automated methods based on automatic speech recognition and natural language processing algorithms, leading to the 3 distinctive linguistic and 2 acoustic patterns of language deterioration and associated composite indexes of their overall severity. Patients were then prospectively followed and received assessments for parkinsonism or dementia during follow-up. The Cox proportional hazard was performed to evaluate the predictive value of language patterns for phenoconversion over a follow-up period of 5 years. RESULTS: Of 180 patients free of parkinsonism or dementia, 156 provided follow-up information. After a mean follow-up of 2.7 years, 42 (26.9%) patients developed neurodegenerative disease. Patients with higher severity of linguistic abnormalities (hazard ratio [HR = 2.35]) and acoustic abnormalities (HR = 1.92) were more likely to develop a defined neurodegenerative disease, with converters having lower content richness (HR = 1.74), slower articulation rate (HR = 1.58), and prolonged pauses (HR = 1.46). Dementia-first (n = 16) and parkinsonism-first with mild cognitive impairment (n = 9) converters had higher severity of linguistic abnormalities than parkinsonism-first with normal cognition converters (n = 17). INTERPRETATION: Automated language analysis might provide a predictor of phenoconversion from iRBD into synucleinopathy subtypes with cognitive impairment, and thus can be used to stratify patients for neuroprotective trials. ANN NEUROL 2024;95:530-543.

Toward an Integrative Approach to the Study of Positive-Affect-Related Aggression.

Research on aggression usually aims at gaining a better understanding of its more negative aspects, such as the role and effects of aversive social interactions, hostile cognitions, or negative affect. However, there are conditions under which an act of aggression can elicit a positive affective response, even among the most nonviolent of individuals. One might experience the "sweetness of revenge" on reacting aggressively to a betrayal or social rejection. A soldier may feel elated after "shooting to kill" in the name of the flag. There are many factors that contribute to the appeal of aggression, but despite growing interest in researching these phenomena, there is still no unitary framework that organizes existing theories and empirical findings and can be applied to a model to generate testable hypotheses. This article presents a narrative review of the literature on positive-affect-related forms of aggression and explores the role of aggression in eliciting positive affect across diverse social situations and relational contexts. An integrative model that unifies existing theories and findings is proposed, with the objective to inspire and inform future research.

Is REM Sleep Behavior Disorder Changing? Secular Changes Versus Referral Patterns.

Background: Since 2014, there has been increasing public outreach effort regarding isolated/idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) in Montreal. Objective: To assess if, over time, milder iRBD cases are presenting earlier. Methods: Disease-free survival was compared in two iRBD recruitment epochs: 2004 to 2013 ("earlier") versus 2014to 2022 ("later") and by referral type ("self-referral" vs. "conventional-referral") in three large centers. Results: In Montreal, among 209 subjects followed prospectively, shorter time to phenoconversion was observed in the earlier epoch (5-year phenoconversion = 42% earlier vs. 23% later); diagnosis before 2014 had a 1.8-fold phenoconversion hazard. However, no difference was observed in 248 subjects from Barcelona and 166 from Innsbruck. Analysis of Montreal data found that increased survival in the later epoch was driven by an increasing number of self-referrals, who phenoconverted at 1/3 the rate of physician-referred subjects. Conclusions: Increased patient awareness of iRBD results in earlier presentation to clinical attention, with a longer time to phenoconversion.

Frequency of Orthostatic Hypotension in Isolated REM Sleep Behavior Disorder.

BACKGROUND AND OBJECTIVES: Although orthostatic hypotension (OH) can be an early feature of autonomic dysfunction in isolated REM sleep behavior disorder (iRBD), no large-scale studies have examined the frequency of OH in iRBD. In this study, we prospectively evaluated the frequency of OH in a large multicenter iRBD cohort. METHODS: Participants 18 years or older with video polysomnogram-confirmed iRBD were enrolled through the North American Prodromal Synucleinopathy consortium. All participants underwent 3-minute orthostatic stand testing to assess the frequency of OH, and a Δ heart rate/Δ systolic blood pressure (ΔHR/ΔSBP) ratio <0.5 was used to define reduced HR augmentation, suggestive of neurogenic OH. All participants completed a battery of assessments, including the Scales for Outcomes in Parkinson Disease-Autonomic Dysfunction (SCOPA-AUT) and others assessing cognitive, motor, psychiatric, and sensory domains. RESULTS: Of 340 iRBD participants (65 ± 10 years, 82% male), 93 (27%) met criteria for OH (ΔHR/ΔSBP 0.37 ± 0.28; range 0.0-1.57), and of these, 72 (77%) met criteria for OH with reduced HR augmentation (ΔHR/ΔSBP 0.28 ± 0.21; range 0.0-0.5). Supine hypertension (sHTN) was present in 72% of those with OH. Compared with iRBD participants without OH, those with OH were older, reported older age of RBD symptom onset, and had worse olfaction. There was no difference in autonomic symptom scores as measured by SCOPA-AUT. DISCUSSION: OH and sHTN are common in iRBD. However, as patients may have reduced autonomic symptom awareness, orthostatic stand testing should be considered in clinical evaluations. Longitudinal studies are needed to clarify the relationship between OH and phenoconversion risk in iRBD. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT03623672; North American Prodromal Synucleinopathy Consortium.

Deep Isolated Aquifer Brines Harbor Atypical Halophilic Microbial Communities in Quebec, Canada.

The deep terrestrial subsurface, hundreds of meters to kilometers below the surface, is characterized by oligotrophic conditions, dark and often anoxic settings, with fluctuating pH, salinity, and water availability. Despite this, microbial populations are detected and active, contributing to biogeochemical cycles over geological time. Because it is extremely difficult to access the deep biosphere, little is known about the identity and metabolisms of these communities, although they likely possess unknown pathways and might interfere with deep waste deposits. Therefore, we analyzed rock and groundwater microbial communities from deep, isolated brine aquifers in two regions dating back to the Ordovician and Devonian, using amplicon and whole genome sequencing. We observed significant differences in diversity and community structure between both regions, suggesting an impact of site age and composition. The deep hypersaline groundwater did not contain typical halophilic bacteria, and genomes suggested pathways involved in protein and hydrocarbon degradation, and carbon fixation. We identified mainly one strategy to cope with osmotic stress: compatible solute uptake and biosynthesis. Finally, we detected many bacteriophage families, potentially indicating that bacteria are infected. However, we also found auxiliary metabolic genes in the viral genomes, probably conferring an advantage to the infected hosts.

HLA in isolated REM sleep behavior disorder and Lewy body dementia.

Synucleinopathies-related disorders such as Lewy body dementia (LBD) and isolated/idiopathic REM sleep behavior disorder (iRBD) have been associated with neuroinflammation. In this study, we examined whether the human leukocyte antigen (HLA) locus plays a role in iRBD and LBD. In iRBD, HLA-DRB1*11:01 was the only allele passing FDR correction (OR = 1.57, 95% CI = 1.27-1.93, p = 2.70e-05). We also discovered associations between iRBD and HLA-DRB1 70D (OR = 1.26, 95%CI = 1.12-1.41, p = 8.76e-05), 70Q (OR = 0.81, 95%CI = 0.72-0.91, p = 3.65e-04) and 71R (OR = 1.21, 95%CI = 1.08-1.35, p = 1.35e-03). Position 71 (pomnibus = 0.00102) and 70 (pomnibus = 0.00125) were associated with iRBD. Our results suggest that the HLA locus may have different roles across synucleinopathies.

Conditions for the origin of homochirality in primordial catalytic reaction networks.

We study the generation of homochirality in a general chemical model (based on the homogeneous, fully connected Smoluchowski aggregation-fragmentation model) that obeys thermodynamics and can be easily mapped onto known origin of life models (e.g. autocatalytic sets, hypercycles, etc.), with essential aspects of origin of life modeling taken into consideration. Using a combination of theoretical modeling and numerical simulations, we look for minimal conditions for which our general chemical model exhibits spontaneous mirror symmetry breaking. We show that our model spontaneously breaks mirror symmetry in various catalytic configurations that only involve a small number of catalyzed reactions and nothing else. Of particular importance is that mirror symmetry breaking occurs in our model without the need for single-step autocatalytis or mutual inhibition, which may be of relevance for prebiotic chemistry.