Search

Sergio L Schmidt,1,2 Michele Santos da Silva,2 Juliana J Schmidt,2 Ana Lucia Novais Carvalho,3 Claudia Cristina Ferreira Vasconcelos,2 Renata Alves Paes,2 Yolanda EM Boechat,4 Rafael Neder,2 Regina P Alvarenga2 1Department of Neurophysiology, State University of Rio de Janeiro, RJ, Brazil; 2Neurology Department, Federal University of the State of Rio de Janeiro, RJ, Brazil; 3Department of Psychology, Fluminense Federal University, Niteroi, Brazil; 4Department of Internal Medicine, Fluminense Federal University, Niteroi, Brazil Background: In the early phases of multiple sclerosis (MS), patients exhibit slight neuropsychiatric deficits that can only be detected using reliable tools. Aim: The present investigation aimed to examine neuropsychological performance in 35 patients with incipient MS. Patients and methods: For the MS group, the inclusion criteria included time of disease

Sergio L Schmidt,1,2 Ana Lucia Novais Carvaho,3 Eunice N Simoes2 1Department of Neurophysiology, State University of Rio de Janeiro, Rio de Janeiro, 2Neurology Department, Federal University of the State of Rio de Janeiro, Rio de Janeiro, 3Department of Psychology, Fluminense Federal University, Niteroi, Brazil Abstract: The relationship between handedness and attentional performance is poorly understood. Continuous performance tests (CPTs) using visual stimuli are commonly used to assess subjects suffering from attention deficit hyperactivity disorder (ADHD). However, auditory CPTs are considered more useful than visual ones to evaluate classroom attentional problems. A previous study reported that there was a significant effect of handedness on students’ performance on a visual CPT. Here, we examined whether handedness would also affect CPT performance using only auditory stimuli. From an initial sample of 337 students, 11 matched pairs were selected. Repeated ANOVAs showed a significant effect of handedness on attentional performance that was exhibited even in the control group. Left-handers made more commission errors than right-handers. The results were interpreted considering that the association between ADHD and handedness reflects that consistent left-handers are less lateralized and have decreased interhemispheric connections. Auditory attentional data suggest that left-handers have problems in the impulsive/hyperactivity domain. In ADHD, clinical therapeutics and rehabilitation must take handedness into account because consistent sinistrals are more impulsive than dextrals. Keywords: attention, ADHD, consistent left-handers, auditory attention, continuous performance test

Localized surface plasmon resonances of individual sub-wavelength cavities milled in metallic films can couple to each other to form a collective behavior. This coupling leads to a delocalization of the plasmon field at the film surface and drastically alters both the linear and nonlinear optical properties of the sample. In periodic arrays of nanocavities, the coupling results in the formation of propagating surface plasmon polaritons (SPP), eigenmodes extending across the array. When artificially introducing dislocations, defects and imperfections, multiple scattering of these SPP modes can lead to hot-spot formation, intense and spatially confined fluctuations of the local plasmonic field within the array. Here, we study the underlying coupling effects by probing plasmonic modes in well-defined individual triangular dimer cavities and in arrays of triangular cavities with and without artificial defects. Nonlinear confocal spectro-microscopy is employed to map the second harmonic (SH) radiation from these systems. Pronounced spatial localization of the SPP field and significant enhancements of the SH intensity in certain, randomly distributed hot spots by more than an order of magnitude are observed from the triangular arrays as compared to a bare silver film by introducing a finite degree of disorder into the array structure. Hot-spot formation and the resulting enhancement of the nonlinear efficiency are correlated with an increase in the lifetime of the localized SPP modes. By using interferometric SH autocorrelation measurements, we reveal lifetimes of hot-spot resonances in disordered arrays that are much longer than the few-femtosecond lifetimes of the localized surface plasmon resonances of individual nanocavity dimers. This suggests that hot spot lifetime engineering provides a path for manipulating the linear and nonlinear optical properties of nanosystems by jointly exploiting coherent couplings and tailored disorder.

Background: The authors conducted a comprehensive review and integration of insights from 4 webinars hosted by the International Society for the Advancement of Spine Surgery (ISASS) to arrive at recommendations for best clinical practices for guideline development for endoscopic spine surgery. This perspective article discusses the limitations of traditional surgical trials and amalgamates surgeons' experience and research on various cutting-edge techniques., Methods: Data were extracted from surveys conducted during each webinar session involving 3639 surgeons globally. The polytomous Rasch model was employed to analyze responses, ensuring a robust statistical assessment of surgeon endorsements and educational impacts and focusing on operative nuances and experience-based outcomes. Bias detection was performed using the differential item functioning test., Results: The ISASS webinars provided a dynamic platform for discussing advances in endoscopic spine surgery, identifying a range of high-value procedures from basic discectomies to complex lumbar interbody fusions. Each high-value endoscopic spine surgery was highlighted in separate peer-reviewed publications, which form the basis for this summary document that synthesizes key takeaways from these webinars. High-value clinical applications of endoscopic spine surgery, primarily defined as higher-intensity endorsement transformation from the pre- to postwebinar survey with a shift to higher mean logit locations of test items both with unbiased and orderly threshold progression, were: (a) Percutaneous interlaminar endoscopic decompression for lateral canal stenosis, (b) transforaminal debridement of low-grade degenerative spondylolisthesis, (c) transforaminal full-endoscopic interbody fusion for hard disc herniation, (d) endoscopic standalone lumbar interbody fusion, (e) endoscopic debridement of spondylolytic spondylolisthesis, and (f) posterior cervical foraminotomy for herniated disc and bony stenosis., Conclusions: The ISASS webinar series has significantly impacted surgeons' education and contributed to the identification of high-value endoscopic spine surgery practices that may serve as a cornerstone for surgeon training standards, policy, and guidelines development. Ongoing research on technological advancements and expansions of clinical indications combined with systematic review is expected to refine the recommendations on high-value endoscopic spinal surgeries recommended for enhanced reimbursement., Clinical Relevance: Assessing surgeon confidence and acceptance of endoscopic spinal surgeries using polytomous Rasch analysis., Level of Evidence: Level 2 (inferential) and 3 (observational) evidence because Rasch analysis provides statistical validation of instruments rather than direct clinical outcomes., Competing Interests: Declaration of Conflicting Interests : The authors volunteered their time and internal resources to support the design and conduction of this research study. All authors aided in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. The authors declare no conflict of interest relevant to this research, and there was no personal circumstance or interest that may be perceived as inappropriately influencing the representation or interpretation of reported research results. This research was not compiled to enrich anyone., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2024 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

The advent of ultra-minimally invasive endoscopic spine surgery, characterized by significantly reduced surgery times, minimal blood loss, and minimal tissue trauma, has precipitated a paradigm shift in the preoperative management of patients with cardiac disease undergoing elective spine procedures. This perspective article explores how these advancements have influenced the requirements for preoperative cardiac workups and the protocols surrounding the cessation of anticoagulation and antiplatelet therapies. Traditionally, extensive cardiac evaluations and the need to stop anticoagulation and antiplatelet agents have posed challenges, increasing the risk of cardiac events and delaying surgical interventions. However, the reduced invasiveness of endoscopic spine surgery presents a safer profile for patients with cardiac comorbidities, potentially minimizing the necessity for rigorous cardiac clearance and allowing for more flexible anticoagulation management. This perspective article synthesizes current research and clinical practices to provide a comprehensive overview of these evolving protocols. It also discusses the implications of these changes for patient safety, surgical outcomes, and overall healthcare efficiency. Finally, the article suggests directions for future research, emphasizing the need for updated guidelines that reflect the reduced perioperative risk associated with these innovative surgical techniques. This discussion is pivotal for primary care physicians, surgeons, cardiologists, and the broader medical community in optimizing care for this high-risk patient population.

Human feline leukaemia virus subgroup C receptor-related proteins 1 and 2 (FLVCR1 and FLVCR2) are members of the major facilitator superfamily 1 . Their dysfunction is linked to several clinical disorders, including PCARP, HSAN and Fowler syndrome 2-7 . Earlier studies concluded that FLVCR1 may function as a haem exporter 8-12 , whereas FLVCR2 was suggested to act as a haem importer 13 , yet conclusive biochemical and detailed molecular evidence remained elusive for the function of both transporters 14-16 . Here, we show that FLVCR1 and FLVCR2 facilitate the transport of choline and ethanolamine across the plasma membrane, using a concentration-driven substrate translocation process. Through structural and computational analyses, we have identified distinct conformational states of FLVCRs and unravelled the coordination chemistry underlying their substrate interactions. Fully conserved tryptophan and tyrosine residues form the binding pocket of both transporters and confer selectivity for choline and ethanolamine through cation-π interactions. Our findings clarify the mechanisms of choline and ethanolamine transport by FLVCR1 and FLVCR2, enhance our comprehension of disease-associated mutations that interfere with these vital processes and shed light on the conformational dynamics of these major facilitator superfamily proteins during the transport cycle., (© 2024. The Author(s).)

Considering the variability in individual responses to opioids and the growing concerns about opioid addiction, prescribing opioids for postoperative pain management after spine surgery presents significant challenges. Therefore, this study undertook a novel pharmacogenomics-based in silico investigation of FDA-approved opioid medications. The DrugBank database was employed to identify all FDA-approved opioids. Subsequently, the PharmGKB database was utilized to filter through all variant annotations associated with the relevant genes. In addition, the dpSNP ( https://www.ncbi.nlm.nih.gov/snp/ ), a publicly accessible repository, was used. Additional analyses were conducted using STRING-MODEL (version 12), Cytoscape (version 3.10.1), miRTargetLink.2, and NetworkAnalyst (version 3). The study identified 125 target genes of FDA-approved opioids, encompassing 7019 variant annotations. Of these, 3088 annotations were significant and pertained to 78 genes. During variant annotation assessments (VAA), 672 variants remained after filtration. Further in-depth filtration based on variant functions yielded 302 final filtered variants across 56 genes. The Monoamine GPCRs pathway emerged as the most significant signaling pathway. Protein-protein interaction (PPI) analysis revealed a fully connected network comprising 55 genes. Gene-miRNA Interaction (GMI) analysis of these 55 candidate genes identified miR-16-5p as a pivotal miRNA in this network. Protein-Drug Interaction (PDI) assessment showed that multiple drugs, including Ibuprofen, Nicotine, Tramadol, Haloperidol, Ketamine, L-Glutamic Acid, Caffeine, Citalopram, and Naloxone, had more than one interaction. Furthermore, Protein-Chemical Interaction (PCI) analysis highlighted that ABCB1, BCL2, CYP1A2, KCNH2, PTGS2, and DRD2 were key targets of the proposed chemicals. Notably, 10 chemicals, including carbamylhydrazine, tetrahydropalmatine, Terazosin, beta-methylcholine, rubimaillin, and quinelorane, demonstrated dual interactions with the aforementioned target genes. This comprehensive review offers multiple strong, evidence-based in silico findings regarding opioid prescribing in spine pain management, introducing 55 potential genes. The insights from this report can be applied in exome analysis as a pharmacogenomics (PGx) panel for pain susceptibility, facilitating individualized opioid prescribing through genotyping of related variants. The article also points out that African Americans represent an important group that displays a high catabolism of opioids and suggest the need for a personalized therapeutic approach based on genetic information., (© 2024. The Author(s).)

Study Objectives: In patients with obstructive sleep apnea (OSA), a previous study using a Go/No-Go task reported an average attention deficit. However, the temporal dynamics of such a deficit are unknown. Here, we investigated whether attention deficits in different subdomains increased as the test progressed. We also investigated the effect of target frequency and speed of stimulus presentation on performance., Methods: Twenty-seven untreated people with OSA and 27 age- and sex-matched controls underwent a 15-minute Go/No-Go task, divided into 6 blocks. Each block was subdivided into 3 different interstimulus intervals (1, 2, and 4 seconds). Three blocks had a low and three had a high target probability (20% and 80%, respectively). Reaction time (alertness), variability of reaction time (sustained attention), commission errors (response inhibition), and omission errors (focused attention) were measured., Results: Alertness was lower in the group with OSA compared with controls, as evidenced by a significantly higher average reaction time. This effect was seen from the start of the task and continued until the end but did not increase in test progression. The temporal pattern of intrinsic alertness deficits in patients with OSA was found to be independent of target frequency or interstimulus interval., Conclusions: The primary attention problem in OSA is on the alertness subdomain irrespective of the number of required responses or speed of stimulus presentation. The present results support the notion that OSA is distinct from other neurological and psychiatric conditions, such as depression or chronic pain. The results also suggest significant concerns regarding daily life activities (eg, driving)., Citation: de Souza Bezerra ML, van Duinkerken E, Simões E, Schmidt SL. General low alertness in people with obstructive sleep apnea. J Clin Sleep Med . 2024;20(5):689-698., (© 2024 American Academy of Sleep Medicine.)

Continuous deep brain stimulation (cDBS) of the subthalamic nucleus (STN) or globus pallidus is an effective treatment for the motor symptoms of Parkinson's disease. The relative benefit of one region over the other is of great interest but cannot usually be compared in the same patient. Simultaneous DBS of both regions may synergistically increase the therapeutic benefit. Continuous DBS is limited by a lack of responsiveness to dynamic, fluctuating symptoms intrinsic to the disease. Adaptive DBS (aDBS) adjusts stimulation in response to biomarkers to improve efficacy, side effects, and efficiency. We combined bilateral DBS of both STN and globus pallidus (dual target DBS) in a prospective within-participant, clinical trial in six patients with Parkinson's disease (n = 6, 55-65 years, n = 2 females). Dual target cDBS was tested for Parkinson's disease symptom control annually over 2 years, measured by motor rating scales, on time without dyskinesia, and medication reduction. Random amplitude experiments probed system dynamics to estimate parameters for aDBS. We then implemented proportional-plus-integral aDBS using a novel distributed (off-implant) architecture. In the home setting, we collected tremor and dyskinesia scores as well as individualized β and DBS amplitudes. Dual target cDBS reduced motor symptoms as measured by Unified Parkinson's Disease Rating Scale (UPDRS) to a greater degree than either region alone (P < 0.05, linear mixed model) in the cohort. The amplitude of β-oscillations in the STN correlated to the speed of hand grasp movements for five of six participants (P < 0.05, Pearson correlation). Random amplitude experiments provided insight into temporal windowing to avoid stimulation artefacts and demonstrated a correlation between STN β amplitude and DBS amplitude. Proportional plus integral control of aDBS reduced average power, while preserving UPDRS III scores in the clinic (P = 0.28, Wilcoxon signed rank), and tremor and dyskinesia scores during blinded testing at home (n = 3, P > 0.05, Wilcoxon ranked sum). In the home setting, DBS power reductions were slight but significant. Dual target cDBS may offer an improvement in treatment of motor symptoms of Parkinson's disease over DBS of either the STN or globus pallidus alone. When combined with proportional plus integral aDBS, stimulation power may be reduced, while preserving the increased benefit of dual target DBS., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Burnout syndrome is characterized by exhaustion, cynicism, and reduced effectiveness. Workers with high burnout scores who continue their professional activities are identified as experiencing non-clinical burnout (NCB), which includes early stages where burnout symptoms (BNS) are present but not yet severe enough to necessitate work leave. This study aimed to investigate the impact of BNS on attention performance among healthcare workers (HCWs) at a COVID-19 reference hospital during the pandemic. The Maslach Burnout Inventory (MBI) was applied to assess the three burnout dimensions. The Continuous Visual Attention Test (CVAT) evaluated four different attention subdomains. Participants were divided into two groups based on their scores on the MBI: controls and NCB. Thirteen controls were matched with 13 NCB subjects based on age, sex, and HCW category. This sample ( n = 26, 65% male) consisted of 11 physicians and 15 nursing professionals with a mean age of 35.3 years (standard deviation = 5.47). NCB subjects had higher impulsivity than controls. There were not any significant group differences in the other attention subdomains. We found significant correlations between impulsivity and all burnout dimensions: higher absolute scores in BNS are associated with higher impulsivity. We concluded that NCB leads to executive attention deficits.

Objective: Depressive symptoms can be assessed with self-reported questionnaires, such as the Patient Health Questionary-9 (PHQ-9). Previous studies have suggested that the PHQ-9 items can be grouped into somatic and non-somatic clusters. However, the classification of the PHQ-9 item "concentration difficulties" into somatic or non-somatic is still controversial. This controversy may be explained by difficulties experienced by subjects in accurately evaluating their attention problems. The primary objective of this study was to determine the correlation between objective attentional performance and the two clusters of depressive symptoms in hospital employees working in stressful conditions., Methods: The participants filled out the PHQ-9 to identify their depressive symptoms. Based on the PHQ-9, the somatic or non-somatic symptoms were measured without considering the question about subjective concentration difficulties. Then, a brief version of the Continuous Visual Attention Test (CVAT) was applied to assess four attentional subdomains. The CVAT is a Go/No-go task that measures number of correct responses (focused attention), number of incorrect responses (behavior-inhibition), average reaction time of correct responses (RT-alertness), and variability of reaction time (VRT-sustained attention). The entire task lasted 90 s. Correlation analyses assessed the relationships between attentional performance and the two dimensions of depressive symptoms., Results: After applying the inclusion/exclusion criteria, 359 individuals were selected. Their age ranged from 20 to 70 years (mean = 40.5, SD = 10.37), and the majority was female (67.6%). A predominance in somatic depressive symptoms was present in 231 (64%) participants, whereas 59 (16%) showed a predominance of non-somatic symptoms. Sixty-nine participants (20%) did not show any predominance. Higher somatic scores were associated with higher RTs, whereas higher non-somatic scores were related to an increase in the number of incorrect responses., Conclusion: The predominance of the somatic cluster was related to lower alertness, whereas the predominance of non-somatic cluster was associated with impulsivity/hyperactivity. This result may explain the difficulties associated with correctly classifying the item concentration difficulties. A brief attentional task can be used as an auxiliary tool to correctly identify the different dimensions of attention that are associated with different clusters of depressive symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Taboada Gjorup, Tolentino Júnior, van Duinkerken, Marques, do Carmo Filho, Joaquim, Neves and Schmidt.)

Background: Traditional deep brain stimulation (DBS) at fixed regular frequencies (>100 Hz) is effective in treating motor symptoms of Parkinson's disease (PD). Temporally non-regular patterns of DBS are a new parameter space that may help increase efficacy and efficiency., Objective: To compare the effects of temporally non-regular patterns of DBS to traditional regularly-spaced pulses., Methods: We simultaneously recorded local field potentials (LFP) and monitored motor symptoms (tremor and bradykinesia) in persons with PD during DBS in subthalamic nucleus (STN). We quantified both oscillatory activity and DBS local evoked potentials (DLEPs) from the LFP., Results: Temporally non-regular patterns were as effective as traditional pulse patterns in modulating motor symptoms, oscillatory activity, and DLEPs. Moreover, one of our novel patterns enabled recording of longer duration DLEPs during clinically effective stimulation., Conclusions: Stimulation gaps of 50 ms can be used to increase efficiency and to enable regular assessment of long-duration DLEPs while maintaining effective symptom management. This may be a promising paradigm for closed-loop DBS with biomarker assessment during the gaps., Competing Interests: Declaration of competing interest In the past 3 years, TAS has received consultant income from Edelson PC (Chicago, IL), Wicker Smith (Naples, FL), Gjording Fouser (Boise, ID), Thorsnes Bartolotta McGuire (San Diego, CA), Cracken Law (Dallas, TX), Matthews Law (Houston, TX), Segal Law (Charleston, WV), Armstrong Teasdale (St. Louis, MO), CNA Continental Casualty Company (Chicago, IL), The National Association of Attorneys General (Washington, DC) and the State of Arizona. WMG holds equity in Deep Brain Innovations, LLC, and NDI Healthcare Fund, LLC, and receives royalties from licensing of intellectual property on temporal patterns of brain stimulation., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Neurotropism of the hepatitis C virus (HCV) can be the source of subtle neuropsychological symptoms in non-cirrhotic patients. Age is a risk factor for cognitive impairment (CI). Thus, asymptomatic elderly people who carry HCV might be at a greater risk of CI. Education can influence test performance., Objectives: (1) To verify whether elderly people with HCV performed poorer than controls on cognitive tests. (2) To analyze how education affects performance. (3) To verify whether the extent of the effect of education on performance depends on the group (HCV vs. controls) and the type of cognitive test., Methods: Asymptomatic HCV carriers older than 60 years ( n = 41) were matched with 41 corresponding controls. All participants performed the following tests: Mini-Cog, Mini Mental State Examination, clock drawing test (CDT), and verbal fluency., Results: (1) There were no significant differences in cognitive performance between the two groups. (2) Higher education was always associated with better performance. (3) There was a significant group difference in the slopes of the regression lines between years of education and CDT performance. No differences were found for the other three tests., Conclusion: Considering the scores on the CDT, the rate of improvement in performance when schooling increases is higher in HCV carriers.

Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis, hepatocellular carcinoma, and liver-related deaths. It is estimated that 40-74% of patients with hepatitis C will experience at least one extrahepatic manifestation within their lifetime. The finding of HCV-RNA sequences in post-mortem brain tissue raises the possibility that HCV infection may affect the central nervous system and be the source of subtle neuropsychological symptoms, even in non-cirrhotic. Our investigation aimed to evaluate whether asymptomatic, HCV-infected subjects showed cognitive dysfunctions. Twenty-eight untreated asymptomatic HCV subjects and 18 healthy controls were tested using three neuropsychological instruments in a random sequence: Symbol Digit Modalities Test (SDMT), Controlled Oral Word Association Test (COWAT), and Continuous Visual Attention Test (CVAT). We performed depression screening, liver fibrosis assessment, blood tests, genotyping, and HCV-RNA viral load. A MANCOVA and univariate ANCOVAS were performed to examine group differences (HCV vs. healthy controls) in four scores of the CVAT (omission errors, commission errors, reaction time-RT, and variability of RT-VRT), and the scores derived from the SDMT, and the COWAT. A discriminant analysis was performed to identify which test variables effectively discriminate HCV-infected subjects from healthy controls. There were no group differences in the scores of the COWAT, SDMT, and in two variables of the CVAT (omission and commission errors). In contrast, the performance of the HCV group was poorer than the controls in RT ( p = 0.047) and VRT ( p = 0.046). The discriminant analysis further indicated that the RT was the most reliable variable to discriminate the two groups with an accuracy of 71.7%. The higher RT exhibited by the HCV group may reflect deficits in the intrinsic-alertness attention subdomain. As the RT variable was found to be the best discriminator between HCV patients and controls, we suggest that intrinsic-alertness deficits in HCV patients may affect the stability of response times increasing VRT and leading to significant lapses in attention. In conclusion, HCV subjects with mild disease showed deficits in RT and intraindividual VRT as compared to healthy controls.

Competing Interests: Drs. Ahn and Taormina are the 2023-2024 Obesity Medicine Fellow representatives to the Obesity Medicine Fellowship Council (OMFC). Dr. Tchang, an OMFC member, co-directs the Obesity Medicine fellowship program at Weill Cornell Medicine, and Drs. Srivastava, Schmidt and Kaplan currently serve as the Vice-Chair, Administrative Director, and Chair of the OMFC, respectively.

Background: The cognitive impairment associated with the COVID-19 pandemic highlighted the need for teleneuropsychology (1). Moreover, neurologic diseases associated with mental deterioration usually require the use of the same neuropsychological instrument to assess cognitive changes across time. Therefore, in such cases, a learning effect upon retesting is not desired. Attention and its subdomains can be measured using Go/no-go tests, such as, the Continuous Visual Attention Test (CVAT). Here, we administered the CVAT to investigate the effect of modality (online vs. face-to-face) on attentional performance. The variables of the CVAT measures four attention domains: focused-attention, behavioral-inhibition, intrinsic-alertness (reaction time, RT), and sustained-attention (intra-individual variability of RTs, VRT)., Methods: The CVAT was applied face-to face and online in 130 adult Americans and 50 adult Brazilians. Three different study designs were used: (1) Between-subjects design: healthy Americans were tested face-to-face ( n  = 88) or online ( n  = 42). We verified if there were any differences between the two modalities. (2) Within-subjects design: Brazilians participants ( n  = 50) were tested twice (online and face-to-face). For each CVAT variable, repeated measures ANCOVAs were performed to verify whether modality or first vs. second tests differ. Agreement was analyzed using Kappa, intraclass correlation coefficients, and Bland-Altman plots. (3) Paired comparisons: we compared Americans vs. Brazilians, pairing subjects by age, sex, and level of education, grouping by modality., Results: Assessment modality did not influence performance using two independent samples (between-subjects design) or the same individual tested twice (within-subjects design). The second test and the first test did not differ. Data indicated significant agreements for the VRT variable. Based on paired samples, Americans did not differ from Brazilians and a significant agreement was found for the VRT variable., Conclusion: The CVAT can be administered online or face-to-face without learning upon retesting. The data on agreement (online vs. face-to-face, test vs. retest, Americans vs. Brazilians) indicate that VRT is the most reliable variable., Limitations: High educational level of the participants and absence of a perfect balanced within-subjects design., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Negrini and Schmidt.)

Cerebellar manifestations have been described in patients with gluten sensitivity (GS)-related disorders. A better understanding of the neurological manifestations of GS requires the use of neuroimaging techniques. We performed a systematic review on neuroimaging findings in GS patients with cerebellar symptoms. We also included a specific search on neuroimaging findings in GS patients with cerebellar manifestations on a gluten-free diet (GFD). PubMed, Embase, and Bireme were systematically searched to identify studies assessing neuroimaging features of adults with cerebellar manifestations and GS with or without enteropathy on a GFD. Ten studies with a total of 222 adult-GS patients were included. Magnetic resonance imaging was used in 100% of the studies. Cerebellar atrophy was evaluated in 7 studies and observed in 63% of the patients. White matter abnormalities were described in 2 studies. Single-photon emission computed tomography was used in 2 studies, and decreased cerebellar perfusion was detected in 92% of the included patients. No study employed nuclear medicine after the start of GFD. Magnetic resonance spectroscopy (MRS) was performed in 2 studies before and after GFD. An increase in the Naa/Cr ratio in cerebellar vermis was seen in 98% of the cases on a strict GFD. Cerebellar atrophy was found to be a prevalent condition in GS patients. MRS demonstrated to be useful in the follow-up of GS patients with cerebellar manifestations on a GFD. Prospective studies using nuclear medicine imaging are needed to study brain changes in GS patients on a GFD., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The impact of COVID-19 on chronic pain (CP) in non-infected vulnerable South American subjects is unknown. Healthcare workers (HCWs) are at increased risk for CP. During the pandemic, many HCWs with CP kept working. Knowing how cognition is affected by CP in these subjects is an important subject for work safety. The attention domain has a pivotal role in cognition. Previously, the Continuous Visual Attention Test (CVAT) was applied to detect specific attention deficits in fibromyalgia patients. The present investigation described CP prevalence in non-infected Brazilian HCWs during the pandemic and assessed HCWs' attentional performance with the aid of the CVAT. This study was carried out at a reference University Hospital in Rio de Janeiro, Brazil. HCWs of both sexes, aged 20 or older, were interviewed from August to December 2020. A 90-second version of the CVAT was performed. The average reaction time to correct responses and the respective intraindividual reaction time variability for correct responses to target (VRT) was determined. Omission and commission errors were also calculated. Then, for each participant we calculated the Z -scores of the CVAT variables based on the distribution of CVAT performance of 211 healthy subjects (reference-comparison group). HCWs with Z -scores > 1.64 were classified as significantly impaired. From the 154 selected HCWs, 72 reported CP during the pandemic (prevalence = 47%). Post hoc ANCOVAs showed that the average correct VRT was significantly higher in the CP group than in the non-CP group ( F = 4.99, df = 1/150, p = 0.027, η 2 = 0.032). The percentage of participants with impaired VRT performance was 30% ( n = 21) in the CP group and 16% ( n = 13) in the non-CP group. The difference between these two propositions reached significance (χ 2 = 3.96, df = 1, p = 0.047). As VRT is associated with the sustained-attention subdomain, our data suggest that this subdomain is disrupted in the CP group., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schmidt, Araguez, Neves, van Duinkerken, Schmidt, Tolentino and Gjorup.)

Background and Objectives: The goal of this review is to describe the general features, mechanisms, technical recording factors, and clinical applications of brain evoked potentials (EPs) generated by deep brain stimulation (DBS) for Parkinson's disease (PD)., Results: Evoked potentials in response to DBS pulses occur on the timescale of milliseconds and are found both locally at the site of stimulation and remotely in the cortex. DBS evoked potentials arise from a complex integration of antidromic and orthodromic conduction pathway responses, and provide information valuable for understanding the mechanisms and circuits involved in symptom treatment. Furthermore, these signals may provide biomarkers for improving DBS outcomes and function. For example, evoked potentials may have utility as control signals for DBS programming or adaptive DBS. Despite their promise there are still critical gaps in our understanding of the mechanisms by which evoked potentials arise and how these signals may be measured and applied in the clinical setting. Technical challenges of recording a highly transient signal at sufficient resolution without the interference of stimulation artifact present a barrier to understanding better DBS-induced EPs., Conclusions: We describe the current scientific landscape of evoked potentials to facilitate and stimulate further investigation., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Sensing technology, as well as cloud communication, is enabling the development of closed-loop deep brain stimulation (DBS) for Parkinson's disease. The accelerometer is a practical sensor that can provide information about the disease/health state of the patient as well as physical activity levels, all of which in the long-term can provide feedback information to an adaptive closed-loop control algorithm for more effective and personalized DBS therapy. In this paper, we present for the first time, acceleration streamed from Medtronic's RC+S device in patients with Parkinson's disease while at home, and compare it to accel-eration acquired concurrently from the patient's Apple Watch. We examined correlation between the accelerometer signals at varying time scales. We also compared the spectral band power obtained from the two accelerometers. While there was an average correlation of 0.37 for subject 1 and 0.50 for subject 2 between the two acceleration signals on a time scale of 10 minutes, the correlation was lower for shorter time scales on the order of seconds. There was greater spectral power in the Parkinsonian tremor band of 4-7 Hz for the externally worn accelerometer than the internal accelerometer, but the internal accelerometer showed greater relative power distributed in the higher frequencies (7-30 Hz). Thus, based on this preliminary analysis, we expect that the internal accelerometer may be used to assess patient activity and state for closed loop DBS but tremor detection may require more sophisticated signal processing. Furthermore, the internal accelerometer may contain information in higher frequency bands that reveal information about the patient state. Clinical relevance - Closed-loop DBS is expected to improve patient outcomes for the tens of thousands of Parkinson's disease patients using DBS [1], [2]. Eliminating an additional external device in order to implement closed-loop adaptive deep brain stimulation would benefit DBS patients however an understanding of what information is lost by doing so is needed to justify the ultimate design of closed-loop DBS.

Background: Deep brain stimulation (DBS) is an effective therapy in advanced Parkinson disease (PD). Although both subthalamic nucleus (STN) and globus pallidus (GP) DBS show equivalent efficacy in PD, combined stimulation may demonstrate synergism., Objective: To evaluate the clinical benefit of stimulating a combination of STN and GP DBS leads and to demonstrate biomarker discovery for adaptive DBS therapy in an observational study., Methods: We performed a pilot trial (n = 3) of implanting bilateral STN and GP DBS leads, connected to a bidirectional implantable pulse generator (Medtronic Summit RC + S; NCT03815656, IDE No. G180280). Initial 1-year outcome in 3 patients included Unified PD Rating Scale on and off medications, medication dosage, Hauser diary, and recorded beta frequency spectral power., Results: Combined DBS improved PD symptom control, allowing >80% levodopa medication reduction. There was a greater decrease in off-medication motor Unified PD Rating Scale with multiple electrodes activated (mean difference from off stimulation off medications -18.2, range -25.5 to -12.5) than either STN (-12.8, range -20.5 to 0) or GP alone (-9, range -11.5 to -4.5). Combined DBS resulted in a greater reduction of beta oscillations in STN in 5/6 hemispheres than either site alone. Adverse events occurred in 2 patients, including a small cortical hemorrhage and seizure at 24 hours postoperatively, which resolved spontaneously, and extension wire scarring requiring revision at 2 months postoperatively., Conclusion: Patients with PD preferred combined DBS stimulation in this preliminary cohort. Future studies will address efficacy of adaptive DBS as we further define biomarkers and control policy., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Few studies have reported specific attention deficits in post-COVID-19 patients. Attention consists of different subdomains. Disruptions to specific attention subdomains might impair a wide range of everyday tasks, including road safety. As there are millions of COVID-19 patients with different socio-economic backgrounds, screening of attentional performance less dependent on education is needed. Here, we verified if physically recovered COVID-19 inpatients showed specific attention decrements at discharge. The Continuous Visual Attention Test (CVAT) is a Go/No-go task which is independent of participants' schooling. It detects visuomotor reaction time (RT = intrinsic alertness), variability of reaction time (VRT = sustained attention), omission (focused-attention), and commission errors (response-inhibition). Thirty physically functional COVID-19 inpatients at discharge and 30 non-infected controls underwent the CVAT. A MANCOVA was performed to examine differences between controls and patients, followed by post-hoc ANCOVAs. Then, we identified the percentile score for each patient within the distribution of the CVAT performance of 211 subjects mentally capable of driving (reference group). COVID-19 patients at discharge showed greater RT and VRT, and more omission errors than controls. Twenty-two patients (73%) had performance below the 5th percentile of the reference group in one or more subdomains. As slow visuomotor RT, deficits in focusing and difficulties in keeping visual attention are associated with traffic accidents, we concluded that most COVID-19 patients at discharge had deficits that may increase the risk of road injuries. As these deficits will probably affect other daily activities, a routine assessment with the CVAT could provide useful information on whom to send to post-COVID centers., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Anxiety symptoms (AS) are exacerbated in healthcare workers (HCWs) during the COVID-19 pandemic. Spirituality is known to protect against AS in the general population and it is a construct that differs from religion. It can be assessed using structured questionnaires. A validated questionnaire disclosed three spirituality dimensions: peace, meaning, and faith. In HCWs we investigated the predictors of chronic anxiety (pre-COVID-19 and during the pandemic) and acute anxiety (only during the pandemic), including spirituality in the model. Then, we verified which spirituality dimensions predicted chronic and acute anxiety. Lastly, we studied group differences between the mean scores of these spirituality dimensions., Material and Methods: The study was carried out in a Brazilian Hospital. HCWs (n = 118) were assessed for spirituality at a single time-point. They were also asked about AS that had started pre-COVID-19 and persisted during the pandemic (chronic anxiety), and AS that had started only during the pandemic (acute anxiety). The subjects without chronic anxiety were subdivided into two other groups: acute anxiety and without chronic and acute anxiety. Forward stepwise logistic regressions were used to find the significant AS predictors. First, the model considered sex, age, religious affiliation, and spirituality. Then, the analysis were performed considering only the three spirituality dimensions. Group means differences in the spirituality dimensions were compared using univariate ANCOVAS followed by T-tests., Results: Spirituality was the most realible predictor of chronic (OR = 0.818; 95%CI:0.752-0.890; p<0.001) and acute anxiety (OR = 0.727; 95%CI:0.601-0.881; p = 0.001). Peace alone predicted chronic anxiety (OR = 0.619; 95%CI:0.516-0.744; p<0.001) while for acute anxiety both peace (OR:0.517; 95%CI:0.340-0.787; p = 0.002), and faith (OR:0.674; 95%CI:0.509-0.892; p = 0.006) significantly contributed to the model. Faith was significantly higher in subjects without AS., Conclusion: Higher spirituality protected against chronic and acute anxiety. Faith and peace spirituality dimensions conferred protection against acute anxiety during the pandemic., Competing Interests: The authors have declared that no competing interests exist.

Olfactory dysfunction is reported frequently in patients with coronavirus disease 2019. However, an effective treatment for this dysfunction is unknown. The present study evaluated carbamazepine as a treatment option for olfactory dysfunction based on its use in cases of neuralgia, especially of the V cranial nerve. The study included 10 patients with coronavirus disease with olfactory complaints who were part of a cohort of 172 coronavirus disease patients monitored for late neurological manifestations. Carbamazepine was administered for 11 weeks. The adverse effects reported were drowsiness (9/10) and dizziness (2/10); 9 of the 10 patients reported improved olfactory function after carbamazepine treatment. While the role of carbamazepine in the control of post-coronavirus disease olfactory dysfunction could not be confirmed in this study, the satisfactory response observed in most patients in this series suggests that further studies are warranted., (© 2022. Journal of NeuroVirology, Inc.)

Purpose: Immune checkpoint inhibitors show high response rates and durable clinical benefit in microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) tumors. However, 50%-60% do not respond to single-agent anti-programmed death-1/programmed death ligand 1 (PD-1/PD-L1) antibodies, and approximately 50% of responders relapse within 6-12 months. This phase Ib trial evaluated safety and antitumor activity of anti-PD-L1 antibody LY3300054 monotherapy or in combination with anti-TIM-3 antibody LY3321367 in patients with MSI-H/dMMR advanced solid tumors., Patients and Methods: Eligible patients ≥18 years without prior anti-PD-1/PD-L1 therapy received LY3300054 monotherapy ( N = 40) or combination ( N = 20); patients with PD-1/PD-L1 inhibitor-resistant/refractory tumors received the combination ( N = 22). LY3300054 (700 mg) and anti-TIM-3 antibody (cycles 1-2: 1,200 mg, cycle 3 onward: 600 mg) were administered intravenously every 2 weeks. Primary endpoints were safety and tolerability., Results: Eighty-two patients were enrolled. Most had colorectal ( n = 39, 47.6%) or endometrial ( n = 14, 17.1%) tumors. More than 70% of patients in the PD-1/PD-L1 inhibitor-resistant/refractory combination cohort had received ≥3 treatment lines. Treatment-related adverse events (TRAE) occurred in 22 patients (55.0%) receiving monotherapy, 13 (65.0%) in the PD-1/PD-L1 inhibitor-naïve combination cohort, and 6 (27.3%) in the PD-1/PD-L1 inhibitor-resistant/refractory combination cohort. A total of 2 patients (5.0%) receiving monotherapy and 3 (7.1%) receiving the combination experienced grade ≥3 TRAEs. Objective responses occurred in 13 patients (32.5%) with monotherapy, 9 (45.0%) in the PD-1/PD-L1 inhibitor-naïve combination cohort, and 1 patient (4.5%) in the PD-1/PD-L1 inhibitor-resistant/refractory combination cohort., Conclusions: LY3300054 monotherapy and combined LY3300054/anti-TIM-3 had manageable safety profiles. Both regimens showed promising clinical activity against PD-1/PD-L1 inhibitor-naïve MSI-H/dMMR tumors. The combination had limited clinical benefit in patients with PD-1/PD-L1 inhibitor-resistant/refractory MSI-H/dMMR tumors., (©2021 American Association for Cancer Research.)

This study is aimed at assessing differences in basic attentional functioning between substantial and minimal work-related exposure to COVID-19 patients in professionals working in a tertiary referral hospital in Rio de Janeiro, Brazil. Therefore, hospital employees performed a Continuous Visual Attention Test. This test consisted of a 90-second Go/No-Go task with 72 (80%) targets and 18 (20%) nontargets. For each participant, reaction time and intraindividual variability of reaction times of all correct target responses, as well as the number of omission and commission errors, were evaluated. Participants were divided into 2 groups based on their exposure to COVID-19 patients (substantial versus minimal exposure). The substantial exposure group consisted of participants with 24 hours/week or more direct contact with COVID-19 patients. This cut-off was based on the clear division between professionals working and not working with COVID-19 patients and considered that 12-hour and 24-hour daily shifts are common for hospital employees in Brazil. A MANCOVA was performed to examine between-group differences, using age, sleep quality, sex, education level, previous COVID-19 infection, and profession as covariates. Of 124 participants, 80 had substantial exposure and 44 had minimal exposure to COVID-19. The overall MANCOVA reached statistical significance ( P = 0.048). Post hoc ANCOVA analysis showed that the substantial exposure group had a statistically significantly higher intraindividual variability of reaction time of all correct target responses ( P = 0.017, Cohen's  δ = -0.55). This result remained after removing those with a previous COVID-19 infection ( P = 0.010, Cohen's  δ = -0.64) and after matching groups for sample size ( P = 0.004, Cohen's  δ = -0.81). No other variables reached statistical significance. Concluding, hospital professionals with a substantial level of exposure to patients with COVID-19 show a significant attention decrement and, thus, may be at a higher risk of accidental SARS-CoV-2 infection., Competing Interests: No conflicts of interest pertaining to this study were reported., (Copyright © 2021 Eelco van Duinkerken et al.)

Delphi is a scientific method to organize and structure an expert discussion aiming to generate insights on controversial topics with limited information. The technique has seen a rise in publication frequency in various disciplines, especially over the past decades. In April 2021, the term Delphi method yielded 28,200 search hits in Google Scholar for the past five years alone. Given the increasing level of uncertainty caused by rapid technological and social change around the globe, collective expert opinions and assessments are likely to gain even more importance. Therefore, the paper at hand presents technical recommendations derived from a Delphi study that was conducted amid the outbreak of the COVID-19 pandemic in 2020.•The paper comprehensively demonstrates how to prepare, conduct, and analyze a Delphi study. In this regard, it combines several methodological advancements of the recent past (e.g., dissent analyses, scenario analyses) with state-of-the-art impulses from other disciplines like strategic management (e.g., fuzzy clustering), psychology (e.g., sentiment analyses), or clinical trials (e.g., consensus measurement).•By offering insights on the variety of possibilities to exploit Delphi-based data, we aim to support researchers across all disciplines in conducting Delphi studies and potentially expand and improve the method's field of application., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s). Published by Elsevier B.V.)

Celiac disease (CD) is an immune-mediated systemic disorder triggered by gluten and related prolamins in genetically predisposed individuals. Here, we described a case of a 31-year-old Caucasian woman who exhibited cerebellar and psychiatric dysfunctions. The patient underwent single-photon emission computed tomography (SPECT-CT) before and after a gluten-free diet (GFD). There was an improvement in cerebellar perfusion accompanied by a remission of cerebellar manifestations. The maintenance of the psychiatric manifestations was related to the persistence of the hypoperfusion in the frontal lobes. The patient's psychiatric symptoms did not change after 4 months under a GFD in the hospital. To our knowledge, this is the first case that shows the relationship between improvement in cerebellar perfusion and remission of cerebellar clinical manifestations in a CD patient under a GFD.

Our objective was to determine the clinical services offered by American Board of Obesity Medicine (ABOM) Diplomates and whether guideline concordant services varied by clinical practice attributes. We conducted a cross-sectional analysis of the 2019 ABOM Diplomate survey (response rate 19.2%). Respondents (n = 494) self-reported services offered: nutrition, exercise, mental health, minimally invasive bariatric procedures, perioperative bariatric surgical care and FDA-approved anti-obesity medications. We graded concordance of services offered with three evidence-based obesity guidelines, and then conducted bivariate analyses comparing concordance by practice attributes. Most responding ABOM Diplomates offered nutrition (90.1%), exercise (67.8%) and mental health (76.7%). Few offered minimally invasive procedures (24.3%), and most provided perioperative surgical care (63.0%). Most (83.4%) prescribed FDA-approved medications-typically both short- and long-term agents (70.9%). Few Diplomates had low concordance with the American Heart Association/American College of Cardiology/The Obesity Society (AHA/ACC/TOS) guidelines (24.7%). Those who managed more obesity-related conditions and endorsed AHA/ACC/TOS guideline use had higher concordance with these recommendations. No differences in guideline concordance existed by population, clinical effort or location. We found similar findings regarding concordance with ) American Association of Clinical Endocrinologists/American College of Endocrinology and Obesity Medicine Association guidelines. In conclusion, most responding ABOM Diplomates offer evidence-based obesity medicine services. Clinicians may therefore have increased confidence in patient receipt of evidence-based care when referring to an ABOM Diplomate., (© 2020 World Obesity Federation.)

Objective: Studies conducted in developed countries have shown that attentional impairment is commonly seen in patients with major depressive disorders (MDD). There is a lack of studies using culture-free neuropsychological instruments. Additionally, attention consists of different subdomains. Deficits in subdomains have not been investigated in MDD. Studies on subdomains using systematic frameworks are needed. We aimed to verify the percentage of Brazilian MDD patients with attention deficits, using a culture-free instrument; compare different attention subdomains in MDD patients with paired controls; find the subdomain that best discriminated controls from MDD patients., Method: Forty-five unmedicated patients currently with MDD and 45 age- and sex-matched controls participated in the study. Attention performance was measured by a Go/No-go task which detected omission errors, commission errors, reaction time (RT), and variability of reaction time (VRT). These variables assess four specific subdomains: focused attention (omission errors), response inhibition (commission errors), alertness (RT), and sustained attention (VRT). MANCOVAs were used to test group differences and logistic regressions to find the strongest predictor of MDD., Results: Compared with normative data, 73.3% of the patients and 17.7% of the controls exhibited attention deficits, defined as a z-score < 2.0 on two or more subdomains. Depressed patients showed poorer performance in all attention subdomains. The VRT variable was the strongest predictor of MDD. Lapses in attention as the test progresses affected the stability of RTs and increased VRT in MDD patients., Conclusions: A significant proportion of the depressive patients shows attention deficits, as described in developed countries; all attention subdomains are affected in MDD patients; sustained attention is the most affected subdomain. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Rationale: Usual interstitial pneumonia (UIP) is the defining morphology of idiopathic pulmonary fibrosis (IPF). Guidelines for IPF diagnosis conditionally recommend surgical lung biopsy for histopathology diagnosis of UIP when radiology and clinical context are not definitive. A "molecular diagnosis of UIP" in transbronchial lung biopsy, the Envisia Genomic Classifier, accurately predicted histopathologic UIP. Objectives: We evaluated the combined accuracy of the Envisia Genomic Classifier and local radiology in the detection of UIP pattern. Methods: Ninety-six patients who had diagnostic lung pathology as well as a transbronchial lung biopsy for molecular testing with Envisia Genomic Classifier were included in this analysis. The classifier results were scored against reference pathology. UIP identified on high-resolution computed tomography (HRCT) as documented by features in local radiologists' reports was compared with histopathology. Measurements and Main Results: In 96 patients, the Envisia Classifier achieved a specificity of 92.1% (confidence interval [CI],78.6-98.3%) and a sensitivity of 60.3% (CI, 46.6-73.0%) for histology-proven UIP pattern. Local radiologists identified UIP in 18 of 53 patients with UIP histopathology, with a sensitivity of 34.0% (CI, 21.5-48.3%) and a specificity of 96.9% (CI, 83.8-100%). In conjunction with HRCT patterns of UIP, the Envisia Classifier results identified 24 additional patients with UIP (sensitivity 79.2%; specificity 90.6%). Conclusions: In 96 patients with suspected interstitial lung disease, the Envisia Genomic Classifier identified UIP regardless of HRCT pattern. These results suggest that recognition of a UIP pattern by the Envisia Genomic Classifier combined with HRCT and clinical factors in a multidisciplinary discussion may assist clinicians in making an interstitial lung disease (especially IPF) diagnosis without the need for a surgical lung biopsy.

Objective: Continuous performance tests (CPTs) usually utilize visual stimuli. A previous investigation showed that inattention is partially independent of modality, but response inhibition is modality-specific. Here we aimed to compare performance on visual and auditory CPTs in ADHD and in healthy controls. Method: The sample consisted of 160 elementary and high school students (43 ADHD, 117 controls). For each sensory modality, five variables were extracted: commission errors (CEs) and omission errors (OEs), reaction time (RT), variability of reaction time (VRT), and coefficient of variability (CofV = VRT / RT). Results: The ADHD group exhibited higher rates for all test variables. The discriminant analysis indicated that auditory OE was the most reliable variable for discriminating between groups, followed by visual CE, auditory CE, and auditory CofV. Discriminant equation classified ADHD with 76.3% accuracy. Conclusion: Auditory parameters in the inattention domain (OE and VRT) can discriminate ADHD from controls. For the hyperactive/impulsive domain (CE), the two modalities are equally important.

Background: The Clinical Dementia Rating (CDR) scale is commonly used to stage cognitive impairment, despite having educational limitations. In elderly with low education, a previous study has shown that intraindividual variability of reaction time (CV) and commission errors (CE), measured using a culture-free Go/No-Go task, can reliably distinguish early Alzheimer's disease (AD) from mild cognitive impairment (MCI) and healthy controls., Objective: We aimed to extend the clinical utility of this culture-free Go/No-Go task in a sample with high educational disparity., Methods: One hundred and ten participants with a wide range of years of formal education (0-14 years) were randomly selected from a geriatric unit and divided based on their CDR scores into cognitively unimpaired (CDR = 0), MCI (CDR = 0.5), and early AD (CDR = 1). All underwent a 90-s reaction-time test that measured the variables previously found to predict CDR in low educated elderly. Here we added years of formal education (educational level) to the model. Multivariate analyses compared differences in group means using educational level as confounding factor. A confirmatory discriminant analyses was performed, to assess if CDR scores could be predicted by the two Go/No-Go variables in a sample with high educational disparity., Results: Over all three groups, differences in both CE and CV reached statistical significance (p < 0.05). The discriminant analysis demonstrated that CV and CE discriminated cognitively impaired from cognitively normal elderly. These results remained similar when discriminating MCI from cognitively unimpaired elderly., Conclusion: The Go/No-Go task reliably discriminates elderly with MCI from elderly without cognitive impairment independent of educational disparity.

Background: Deep brain stimulation (DBS) is an effective therapy for reducing the motor symptoms of Parkinson's disease, but the mechanisms of action of DBS and neural correlates of symptoms remain unknown., Objective: To use the neural response to DBS to reveal connectivity of neural circuits and interactions between groups of neurons as potential mechanisms for DBS., Methods: We recorded activity evoked by DBS of the subthalamic nucleus (STN) in humans with Parkinson's disease. In follow up experiments we also simultaneously recorded activity in the contralateral STN or the ipsilateral globus pallidus from both internal (GPi) and external (GPe) segments., Results: DBS local evoked potentials (DLEPs) were stereotyped across subjects, and a biophysical model of reciprocal connections between the STN and the GPe recreated DLEPs. Simultaneous STN and GP recordings during STN DBS demonstrate that DBS evoked potentials were present throughout the basal ganglia and confirmed that DLEPs arose from the reciprocal connections between the STN and GPe. The shape and amplitude of the DLEPs were dependent on the frequency and duration of DBS and were correlated with resting beta band oscillations. In the frequency domain, DLEPs appeared as a 350 Hz high frequency oscillation (HFO) independent of the frequency of DBS., Conclusions: DBS evoked potentials suggest that the intrinsic dynamics of the STN and GP are highly interlinked and may provide a promising new biomarker for adaptive DBS., Competing Interests: Declaration of competing interest WMG is cofounder, Director and CSO of Deep Brain Innovations LLC. WMG is Director and CSO of NDI Healthcare Fund and receives compensation for these positions. These relationships are reported to the Conflict of Interest Committee at Duke University., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A specific particularity of neurological diseases in Asia is the relative commonality of neuromyelitis optica (NMO) and Asian type MS (OSMS). Both conditions also occur in South American patients. The Brazilian population differs from the European and the Asian populations due to the mixture of ancestralities between European colonizers and African slaves. To better know the clinical characteristics of Brazilian patients with Asian type MS this study aimed to analyze the clinical, radiological and serological data that would help to distinguish between OSMS and NMO and clarify, in a Non-Asian population, if OSMS is an MS phenotype, an NMO spectrum disorder by 2015 classification, or a complement activating antibody to myelin oligodendrocyte glycoprotein (MOG-IgG) antibody-related disease., Methods: We selected cases retrospectively with NMO and OSMS in the medical registry of patients with idiopathic inflammatory demyelinating diseases under follow-up since 1997 in Federal Hospital da Lagoa, the principal reference center for MS treatment in Rio de Janeiro, Brazil. OSMS has selective involvement of the optic nerve and spinal cord with no cerebral or cerebellar symptoms associated with small spinal cord lesions and negativity for the aquaporin-4 antibody (AQP4-IgG). NMO full-filled the revised criteria (2006) associated with longitudinally extensive transverse myelitis (LETM). We recorded the following data: ethnicity/skin color, neurologic impairment "at nadir" and "at recovery" of the index events (optic neuritis and transverse myelitis), long term disability, mortality, health quality of life scores by the SF-36 questionnaire, CSF IgG oligoclonal bands and serological AQP4-IgG and MOG-IgG antibodies tested by Cell-based assay. The last brain MRIs were classified as either satisfying or not satisfying MAGNIMS radiologic criteria for MS or typical or not typical for NMOSD. The new classification of NMO spectrum disorders (2015) was applied., Results: Forty-one OSMS and 122 NMO cases were analyzed. OSMS affected mainly young white women, causing unilateral optic neuritis and partial myelitis with excellent recovery. After a mean disease duration of 20 years, 90% of the patients had free ambulation, and 70% had a mild disability or no disability. Only 7.2% presented a secondary progressive course, and no deaths occurred. All cases had negativity to AQP4-IgG and MOG-IgG biomarkers. 95% had resonance criteria for MS. OSMS differed from NMO by ethnicity, morbidity, and mortality: most were African descendants, with severe motor and visual dysfunction, and one third died. Only NMO cases full-filled the new NMOSD classification (52 AQP4-IgG positive, 29 AQP4-IgG negative, and 41 AQP4-IgG unknown)., Conclusion: In Brazilian patients, OSMS and NMO are different immune-mediated diseases. OSMS is a milder MS phenotype., Competing Interests: Declaration of Competing Interest The authors have any conflict of interest with the subject of the study., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Neural oscillations represent synchronous neuronal activation and are ubiquitous throughout the brain. Oscillatory activity often includes brief high-amplitude bursts in addition to background oscillations, and burst activity may predict performance on working memory, motor, and comprehension tasks., Objective: We evaluated beta burst activity as a possible biomarker for motor symptoms in Parkinson's disease (PD). The relationship between beta amplitude dynamics and motor symptoms is critical for adaptive DBS for treatment of PD., Methods: We applied threshold-based and support vector machine (SVM) analyses of burst parameters to a defined on/off oscillator and to intraoperative recordings of local field potentials from the subthalamic nucleus of 16 awake patients with PD., Results: Filtering and time-frequency analysis techniques critically influenced the accuracy of identifying burst activity. Threshold-based analysis lead to biased results in the presence of changes in long-term beta amplitude and accurate quantification of bursts with thresholds required unknowable a priori knowledge of the time in bursts. We therefore implemented an SVM analysis, and we did not observe changes in burst fraction, rate, or duration with the application of cDBS in the participant data, even though SVM analysis was able to correctly identify bursts of the defined on/off oscillator., Conclusion: Our results suggest that cDBS of the STN may not change beta burst activity. Additionally, threshold-based analysis can bias the fraction of time spent in bursts. Improved analysis strategies for continuous and adaptive DBS may achieve improved symptom control and reduce side-effects., Competing Interests: Declaration of competing interest WMG is Co-Founder, Director and CSO of Deep Brain Innovations LLC. WMG is director and CSO of NDI Healthcare Fund and receives compensation for this position. These relationships are reported to the Conflict of Interest Committee at Duke University., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Scales for cognitive deterioration usually depend on education level., Objective: We aimed to study the clinical utility of a culture-free Go/No-Go task in a multi-ethnic cohort with low education level., Methods: Sixty-four participants with less than 4 years of formal education were included and divided on the basis of their Clinical-Dementia-Rate scores (CDR) into cognitively unimpaired (CDR = 0), mild cognitive impairment (MCI; CDR = 0.5), and early Alzheimer's disease (AD, CDR = 1). All underwent a 90-s Continuous Visual Attention Test. This test consisted of a 90-s Go/No-go task with 72 (80%) targets and 18 (20%) non-targets. For each participant, reaction times and intraindividual variability of reaction times of all correct target responses, as well as the number of omission and commission errors were evaluated. Coefficient of variability was calculated for each participant by dividing the standard deviation of the reaction times by the mean reaction time. A MANCOVA was performed to examine between-group differences using age and sex as covariates. Discriminate analysis was performed to find the most reliable test-variable to discriminate the three groups., Results: Commission error, intraindividual variability of reaction time, and coefficient of variability progressively worsened with increasing CDR level. Discriminant analysis demonstrated that coefficient of variability was the best discriminant factor, followed by intraindividual variability of reaction time and commission error., Conclusion: The Go/No-Go task was able to discriminate people with MCI or early AD from controls in the setting of illiteracy.

Referees and assistant referees are submitted to high physical stress during matches. Pressure to make decisions in front of large crowds is another potential stressor. These two stressors can impair attention executive control, depending on physical fitness and individual vulnerability or resilience to situational pressure. Error percentage for referees and assistants may reach around 14% during a soccer match. Although previous studies have suggested that soccer referees and assistants should take cognitive assessments, they are only required by Fédération Internationale de Football Association (FIFA) to demonstrate knowledge of the rules and pass annually in a fitness test (FIFA-Test). This study aimed to assess attention performance in referees and assistants before and after the mandatory FIFA-Test. It is hypothesized that the high physical demands associated with the pressure to pass the FIFA-Test would interfere with attention performance. The sample included 33 referees and 20 assistants. The Continuous Visual Attention Test (CVAT) consisted of a 15-min Go/No-go task. Performance in the CVAT is based on four variables: omission and commission errors, reaction time, and variability of reaction time (VRT). Failure in the CVAT was defined by a performance below the 5th percentile of the age- and sex-matched normative data in at least one variable of the CVAT. Before the FIFA-Test all participants performed the CVAT. The second CVAT began 3-7 min directly following completion of the FIFA-test. Considering only the officials who passed both the FIFA-Test and the first CVAT (19 referees and 15 assistants), 44% (9 referees and 6 assistants) exhibited a performance decline in the second CVAT. A significant increase in VRT was found after the high intensity exercise. As increase in VRT is thought to reflect executive dysfunctions and lapses of attention, we concluded that physical fitness alone may not be enough to help officials cope with the physical and contextual stresses associated with the FIFA-Test. These data suggest that over 35% of soccer referees and their assistants who were considered physically able to referee matches may not be mentally prepared for the attentional demands of refereeing soccer matches.

Low-field magnetic stimulation (LFMS) is a gated high-frequency non-invasive brain stimulation method (500 Hz gated at 2 Hz) with a proposed antidepressant effect. However, it has remained unknown how such stimulation paradigms modulate neuronal network activity and how the induced changes depend on network state. Here we examined the immediate and outlasting effects of the gated high-frequency electric field associated with LFMS on the cortical activity as a function of neuromodulatory tone that defines network state. We used a sham-controlled study design to investigate effects of stimulation (20 min of 0.5 s trains of 500 Hz charge-balanced pulse stimulation patterned at 0.5 Hz) on neural activity in mouse medial prefrontal cortex in vitro. Bath application of cholinergic and noradrenergic agents enabled us to examine the stimulation effects as a function of neuromodulatory tone. The stimulation attenuated the increase in firing rate of layer V cortical neurons during the post-stimulation period in the presence of cholinergic activation. The same stimulation had no significant immediate or outlasting effect in the absence of exogenous neuromodulators or in the presence of noradrenergic activation. These results provide electrophysiological insights into the neuromodulatory-dependent effects of gated high-frequency stimulation. More broadly, our results are the first to provide a mechanistic demonstration of how behavioral states and arousal levels may modify the effects of non-invasive brain stimulation., (© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Objective: Continuous Performance Tests (CPTs) are known to measure inattention and impulsivity in students with ADHD. Many CPTs utilize a visual format. It is accepted that auditory tasks reflect attentional demand more closely in the classroom. Thus, the association between deficits found by auditory and visual CPTs needs to be studied. We hypothesized that impulsivity would be dependent on sensory modality and inattention would be a unitary cross-modal construct., Method: Forty-four students with ADHD performed two CPTs (visual and auditory). We analyzed correlations between the variables examined by the two tasks., Results: There were strong correlations between variables measuring inattention. Correlations between auditory and visual measures of impulsivity were weak., Conclusion: Inattention is partially independent of modality. In contrast, response inhibition is modality-specific. Although ADHD is defined regardless of modality, hyperactive students may exhibit deficits in the auditory modality but not in the visual modality or vice versa.

Professional football is a globalized game in which players are the most valuable assets for clubs. In this study, we explore the evolution of the football players' transfer network among 21 European first leagues between the seasons 1996/1997 and 2015/2016. From a topological point of view, we show that this network achieved an upper limit expansion around season 2007/2008, thereafter becoming more connected and dense. Using a machine learning approach based on Self-Organizing Maps and Principal Component Analysis we confirm that European competitions, such as the UEFA Champions League or UEFA Europa League, are indeed a "money game" where the clubs with the highest transfer spending achieve better sportive performance. Some clubs' transfer market activities also affect domestic performance. We conclude from our findings that the relationship between transfer spending and domestic or international sportive performance might lead to substantial inequality between clubs and leagues, while potentially creating a virtuous (vicious) circle in which these variables reinforce (weaken) each other., Competing Interests: The authors have declared that no competing interests exist.

Background: Obstructive sleep apnea (OSA) is characterized by apnea-hypopnea during sleep. Overnight polysomnography (PSG) is usually used to detect the frequency of apneic and hypopneic events. Attention and executive deficits are commonly reported in OSA patients. Previous investigations suggested that cognitive impairments were dependent on attention deficits. However, attention is not a unitary domain and consists of different subdomains such as alertness, sustained attention, focused attention, and executive attention (impulsivity/hyperactivity). Little is known about the attention subdomains affected in OSA. Attention is commonly assessed using continuous performance tests, such as the continuous visual attention test (CVAT). Distinct variables can be derived from the CVAT. Each CVAT variable is associated with a specific attention subdomain. Objective: This study aimed to examine the variables of the CVAT that are affected by OSA and to identify the most reliable CVAT variable that distinguishes OSA from controls via discriminant analysis. Method: Patients scheduled to perform a PSG were invited to participate in this study. Immediately before the PSG, they performed the CVAT. Based on the PSG results, 27 treatment-naïve OSA patients were sampled. The same number of healthy controls were selected to match the two groups by age and gender. Five CVAT variables were examined: commission errors, omission errors, reaction time (RT), variability of reaction time (VRT), and coefficient of variability (VRT/RT). Results: ANCOVAs indicated that RT and VRT were affected by OSA. No difference in accuracy (omission and commission errors) was observed between healthy controls and OSA patients. When the VRT measurements were corrected for their respective RT values (VRT/RT), the mean difference on this coefficient did not reach significance. The discriminant analysis indicated that the two groups could be best differentiated by the RT variable. Conclusions: Attention problems, commonly observed in OSA patients, may reflect a primary problem on the alertness subdomain. The CVAT was able to detect the primary (alertness-RT parameter) and the secondary deficits (sustained attention-VRT parameter) associated with OSA. As there is no learning effect in the condition of retests, the CVAT can be used to assess the cognitive recovery in OSA patients during treatment.

Background: Depression diagnosis requires five or more symptoms (Diagnostic and Statistical Manual of Mental Disorders-DSM-5). One of them must be either Depressed mood or Anhedonia, named main criteria. Although the secondary symptoms can be divided into somatic and non-somatic clusters, the DSM-5 identify depression in all or none fashion. In contrast, depression severity is a continuous variable. Therefore, it is commonly assessed with scales such as the Hamilton Depression Rating Scale (HAMD). Previously, we reported that patients with moderate depression (MD) exhibit greater impairments in cardiac-autonomic modulation than severely depressed (SD) patients. However, clinicians usually do not use scales. Objective: To verify whether the DSM-5 symptoms would be able to discriminate SD from MD and MD from non-depressed (ND) subjects. Material and Methods: Depression was diagnosed based on the Structured Clinical Interview for DSM-5® Disorders. The HAMD evaluated depression severity. In depressed subjects, MD and SD were defined considering the HAMD scores. ND was defined considering both the absence of DSM-5 criteria for depression and the HAMD score. Among 782 outpatients, 46 SD were found. MD and ND subjects were randomly sampled to match the demographic variables of the SD group. Results: Discriminant analysis showed that Depressed Mood was the most reliable symptom to discriminate ND from MD. Anhedonia discriminated SD from MD. Among the secondary DSM-5 criteria, the somatic cluster discriminated ND from MD and the non-somatic cluster SD from MD patients. Discussion: The presence of the somatic cluster in MD may indicate decreased vagal tone and/or increased sympathetic tone, leading to higher cardiovascular risk. As SD is associated with the non-somatic cluster, these patients are at risk of committing suicide. The DSM-5 symptoms exhibited by the patient may help the choice of adequate pharmacological treatment. This would avoid the use of antidepressants that unnecessarily increase cardiac risk in MD. When the symptom cluster suggests SD, the treatment must focus on the prevention of suicide. Conclusions: Depression severity may be inferred based on the DSM-5 criteria. The presence of the Anhedonia main criterium accompanied by non-somatic criteria indicate SD. The Depressive Mood criterium followed by somatic criteria suggest MD.

Hypogonadism in males is associated with increased body fat and altered postprandial metabolism, but mechanisms remain poorly understood. Using a cross-over study design, we investigated the effects of short-term sex hormone suppression with or without testosterone add-back on postprandial metabolism and the fate of dietary fat. Eleven healthy males (age: 29 ± 4.5 year; BMI: 26.3 ± 2.1 kg/m 2 ) completed two 7-day study phases during which hormone levels were altered pharmacologically to produce a low sex hormone condition (gonadotropin releasing hormone antagonist, aromatase inhibitor, and placebo gel) or a testosterone add-back condition (testosterone gel). Following 7 days of therapy, subjects were administered an inpatient test meal containing 50 μCi of [1- 14 C] oleic acid. Plasma samples were collected hourly for 5 h to assess postprandial responses. Energy metabolism (indirect calorimetry) and dietary fat oxidation ( 14 CO 2 in breath) were assessed at 1, 3, 5, 13.5, and 24 h following the test meal. Abdominal and femoral adipose biopsies were taken 24 h after the test meal to determine uptake of the labeled lipid. Postprandial glucose, insulin, free-fatty acid, and triglyceride responses were not different between conditions (P > 0.05). Whole-body energy metabolism was also not different between conditions at any time point (P > 0.05). Dietary fat oxidation trended lower (P = 0.12) and the relative uptake of 14 C labeled lipid into femoral adipose tissue was greater (P = 0.03) in the low hormone condition. Short-term hormone suppression did not affect energy expenditure or postprandial metabolism, but contributed to greater relative storage of dietary fat in the femoral depot. ClinicalTrials.gov Identifier: NCT03289559., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)