Levodopa-Induced Dyskinesia Is Associated with Increased Thyrotropin Releasing Hormone in the Dorsal Striatum of Hemi-Parkinsonian Rats

Background Dyskinesias associated with involuntary movements and painful muscle contractions are a common and severe complication of standard levodopa (L-DOPA, L-3,4-dihydroxyphenylalanine) therapy for Parkinson's disease. Pathologic neuroplasticity leading to hyper-responsive dopamine receptor signaling in the sensorimotor striatum is thought to underlie this currently untreatable condition. Methodology/Principal Findings Quantitative real-time polymerase chain reaction (PCR) was employed to evaluate the molecular changes associated with L-DOPA-induced dyskinesias in Parkinson's disease. With this technique, we determined that thyrotropin releasing hormone (TRH) was greatly increased in the dopamine-depleted striatum of hemi-parkinsonian rats that developed abnormal movements in response to L-DOPA therapy, relative to the levels measured in the contralateral non-dopamine-depleted striatum, and in the striatum of non-dyskinetic control rats. ProTRH immunostaining suggested that TRH peptide levels were almost absent in the dopamine-depleted striatum of control rats that did not develop dyskinesias, but in the dyskinetic rats, proTRH immunostaining was dramatically up-regulated in the striatum, particularly in the sensorimotor striatum. This up-regulation of TRH peptide affected striatal medium spiny neurons of both the direct and indirect pathways, as well as neurons in striosomes. Conclusions/Significance TRH is not known to be a key striatal neuromodulator, but intrastriatal injection of TRH in experimental animals can induce abnormal movements, apparently through increasing dopamine release. Our finding of a dramatic and selective up-regulation of TRH expression in the sensorimotor striatum of dyskinetic rat models suggests a TRH-mediated regulatory mechanism that may underlie the pathologic neuroplasticity driving dopamine hyper-responsivity in Parkinson's disease.Morris K. Udall Center for Excellence in Parkinson’s Research at MGH/MITNational Institutes of Health (U.S.) (NIH NS38372)American Parkinson Disease Association, Inc.University of Alabama at BirminghamMassachusetts General HospitalNational Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (NIDDK/NIH grant R01 DK58148)National Institute of Neurological Disorders and Stroke (U.S.) (R01 NINDS/NIH grant NS045231)Stanley H. and Sheila G. Sydney FundMichael J. Fox Foundation for Parkinson's Researc

The World Amphipoda Database: history and progress

We provide an overview of the World Amphipoda Database (WAD), a global species database that is part of the World Register of Marine Species (WoRMS). Launched in 2013, the database contains entries for over 10,500 accepted species names. Edited currently by 31 amphipod taxonomists, following WoRMS priorities, the WAD has at least one editor per major group. All accepted species are checked by the editors, as is the authorship available for all of the names. The higher classification is documented for every species and a type species is recorded for every genus name. This constitutes five of the 13 priorities for completion, set by WoRMS. In 2015, five LifeWatch grants were allocated for WAD activities. These included a general training workshop in 2016, together with data input for the superfamily Lysianassoidea and for a number of non-marine groups. Philanthropy grants in 2019 and 2021 covered more important gaps across the whole group. Further work remains to complete the linking of unaccepted names, original descriptions, and environmental information. Once these tasks are completed, the database will be considered complete for 8 of the 13 priorities, and efforts will continue to input new taxa annually and focus on the remaining priorities, particularly the input of type localities. We give an overview of the current status of the order Amphipoda, providing counts of the number of genera and species within each family belonging to the six suborders currently recognized

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

The Fabricated Forest

This dissertation approaches historical ecology as reflexive process, tying together archaeology, iconographic analysis, ethnography, and ethnohistory to argue that modern tropical ecosystems are the result of long-term, intentional engagement with human needs and priorites. Civilizational success in these environments, once thought to be marginal zones, required active and sensitive management of arboreal resources. Through a case study at the Late Preclassic and Late Classic inhabited Maya site of San Bartolo, Guatemala, I demonstrate the correspondence between the modern forest and ancient use patterns. The fieldwork component integrated silvicultural and ecohistorical development of the Petén. In conjunction with this interdisciplinary track, laboratory protocols were employed to secure ancient tree species identification on charcoal recovered from Late Classic internal chultún middens and a central plaza offering from the Preclassic period at Grupo Zacatál. Finally, connections are drawn between the archaeological data and iconographic depictions of arboreal elements present in the iconographic depictions from the site’s Preclassic structure, Las Pinturas, sub-1. Situating these remains in local context, I suggest that the canonical images form these mural scenes have connections to canonical images that appear throughout Mesoamerica, the Preclssic artists of San Bartolo connected the mythical actions to local space by adding botanical elements from species in their environment. While a full reconstruction of species exploitation and ancient silvicultural tactics are not possible from the analyses conducted in this dissertation alone, the establishment of silvicultural and archaeobotanical methods in tropical zones represents a crucial step towards more sophisticated analyses of anthropogenic ecological resilience and collapse.Anthropolog

Get a grip : Slippage-robust and glint-free gaze estimation for real-time pervasive head-mounted eye tracking

A key assumption conventionally made by flexible head-mounted eye-tracking systems is often invalid: The eye center does not remain stationary w.r.t. the eye camera due to slippage. For instance, eye-tracker slippage might happen due to head acceleration or explicit adjustments by the user. As a result, gaze estimation accuracy can be significantly reduced. In this work, we propose Grip, a novel gaze estimation method capable of instantaneously compensating for eye-tracker slippage without additional hardware requirements such as glints or stereo eye camera setups. Grip was evaluated using previously collected data from a large scale unconstrained pervasive eye-tracking study. Our results indicate significant slippage compensation potential, decreasing average participant median angular offset by more than 43% w.r.t. a non-slippage-robust gaze estimation method. A reference implementation of Grip was integrated into EyeRecToo, an open-source hardware-agnostic eye-tracking software, thus making it readily accessible for multiple eye trackers (Available at: www.ti.uni-tuebingen.de/perception)

Country roads: travel, visibility, and late classic settlement in the southern Maya Mountains

Mayanist archaeology has long been concerned with creating and evaluating explanatory models for the locations of ancient sites relative to one another and to the physical geography of the Maya world. This study combines epigraphic data and spatial analyses to explore motivations for settlement location and to interrogate territorial strategies in Late Classic (a.d. 600–830) kingdoms in the southern Maya Mountains, around the modern towns of Dolores and Poptún, Guatemala. Least-cost path analyses were used to model natural travel corridors and their relationship with site location was assessed. In conjunction, viewshed analyses were applied to evaluate the importance of visual connections to likely travel routes. The results are considered in the context of the socio-politics and economics of the region, and raise questions about the character of and interconnections between travel, exchange, settlement location, and mechanisms for reinforcing territorial claims in the Late Classic Southern Maya Mountains

Clinical Review of Juvenile Huntington's Disease.

Juvenile Huntington's disease (JHD) is rare. In the first decade of life speech difficulties, rigidity, and dystonia are common clinical motor symptoms, whereas onset in the second decade motor symptoms may sometimes resemble adult-onset Huntington's disease (AOHD). Cognitive decline is mostly detected by declining school performances. Behavioral symptoms in general do not differ from AOHD but may be confused with autism spectrum disorder or attention deficit hyperactivity disorder and lead to misdiagnosis and/or diagnostic delay. JHD specific features are epilepsy, ataxia, spasticity, pain, itching, and possibly liver steatosis. Disease progression of JHD is faster compared to AOHD and the disease duration is shorter, particularly in case of higher CAG repeat lengths. The diagnosis is based on clinical judgement in combination with a positive family history and/or DNA analysis after careful consideration. Repeat length in JHD is usually >  55 and caused by anticipation, usually via paternal transmission. There are no pharmacological and multidisciplinary guidelines for JHD treatment. Future perspectives for earlier diagnosis are better diagnostic markers such as qualitative MRI and neurofilament light in serum

A companion to the preclinical common data elements on neurobehavioral comorbidities of epilepsy: a report of the TASK3 behavior working group of the ILAE/AES Joint Translational Task Force.

The provided companion has been developed by the Behavioral Working Group of the Joint Translational Task Force of the International League Against Epilepsy (ILAE) and the American Epilepsy Society (AES) with the purpose of assisting the implementation of Preclinical Common Data Elements (CDE) for studying and for reporting neurobehavioral comorbidities in rodent models of epilepsy. Case Report Forms (CRFs) are provided, which should be completed on a per animal/per test basis, whereas the CDEs are a compiled list of the elements that should be reported. This companion is not designed as a list of recommendations, or guidelines for how the tests should be run-rather, it describes the different types of assessments, and highlights the importance of rigorous data collection and transparency in this regard. The tests are divided into 7 categories for examining behavioral dysfunction on the syndrome level: deficits in learning and memory; depression; anxiety; autism; attention deficit/hyperactivity disorder; psychosis; and aggression. Correspondence and integration of these categories into the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) is introduced. Developmental aspects are addressed through the introduction of developmental milestones. Discussion includes complexities, limitations, and biases associated with neurobehavioral testing, especially when performed in animals with epilepsy, as well as the importance of rigorous data collection and of transparent reporting. This represents, to our knowledge, the first such resource dedicated to preclinical CDEs for behavioral testing of rodents