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The link between smoking and a lower risk of Parkinson's disease (PD) is one of the strongest environmental or lifestyle associations in neuroepidemiology. Growing evidence supports the hypothesis that the association is based on a neuroprotective effect of smoking on PD, despite the plausible alternative that smoking serves as a marker for a proximal protective influence without itself conferring benefit. But how smoking could protect against neurodegeneration in PD is not well understood. Of several candidate molecules and mechanisms that have been nominated, nicotine has received the most attention. However, randomized controlled clinical trials of nicotine in PD have failed to demonstrate benefit on motor endpoints, including the NIC-PD study in which recently diagnosed participants were randomly assigned to placebo or nicotine treatment for 1 year. Given these results, the time is right to evaluate the neuroprotective potential of other molecules and biochemical cascades triggered by smoking. Here, we review the evidence supporting smoking's possible protective effect on PD, compounds in tobacco and smoke that might mediate such benefit, and non-causal classes of explanation, including reverse causation and the prospect of shared genetic determinants of smoking and PD resistance. The therapeutic potential of non-nicotine components of smoke is suggested by studies supporting multiple alternative mechanisms ranging from monoamine oxidase inhibitors to gut microbiome disruption to antioxidant response induction by chronic exposure to low levels of carbon monoxide. Rigorous investigation is warranted to evaluate this molecule and others for disease-preventing and disease-modifying activity in PD models and, if warranted, in clinical trials. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Nicotina , Doença de Parkinson , Fumar , Humanos , Nicotina/efeitos adversos , Doença de Parkinson/genética , Ensaios Clínicos Controlados Aleatórios como Assunto , Fumantes , Fumar/efeitos adversosRESUMO
Traffic-related pedestrian deaths in the United States reached a 40-year high in 2021. Each year, pedestrians also suffer nonfatal traffic-related injuries requiring medical treatment. Near real-time emergency department visit data from CDC's National Syndromic Surveillance Program during January 2021-December 2023 indicated that among approximately 301 million visits identified, 137,325 involved a pedestrian injury (overall visit proportion = 45.62 per 100,000 visits). The proportions of visits for pedestrian injury were 1.53-2.47 times as high among six racial and ethnic minority groups as that among non-Hispanic White persons. Compared with persons aged ≥65 years, proportions among those aged 15-24 and 25-34 years were 2.83 and 2.61 times as high, respectively. The visit proportion was 1.93 times as high among males as among females, and 1.21 times as high during September-November as during June-August. Timely pedestrian injury data can help collaborating federal, state, and local partners rapidly monitor trends, identify disparities, and implement strategies supporting the Safe System approach, a framework for preventing traffic injuries among all road users.
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Acidentes de Trânsito , Serviço Hospitalar de Emergência , Pedestres , Ferimentos e Lesões , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Acidentes de Trânsito/estatística & dados numéricos , Distribuição por Idade , Visitas ao Pronto Socorro , Serviço Hospitalar de Emergência/estatística & dados numéricos , Pedestres/estatística & dados numéricos , Estados Unidos/epidemiologia , Ferimentos e Lesões/epidemiologia , Etnicidade/estatística & dados numéricos , Grupos Raciais/estatística & dados numéricosRESUMO
BACKGROUND: Vision Zero is a strategy to eliminate traffic fatalities and to promote equitable mobility options for all road users. Using a nationally representative survey, we aimed to estimate the prevalence of Vision Zero action plans or strategies in the USA. METHODS: Municipal officials were surveyed in 2021. In this cross-sectional study, we calculated the prevalence of Vision Zero plans or strategies and compared municipalities with adjusted prevalence ratios (PR) to account for region and sociodemographic characteristics. RESULTS: Among 1955 municipalities participating in the survey (question-specific response rate: 44.3%), the prevalence of a Vision Zero action plan or strategy was 7.7%; 70.5% responded no and 21.8% don't know. Prevalence was 4.8% in small municipalities (1000-2499 residents), 20.3% in medium-large municipalities (50 000-124 999 residents; PR=4.1), and 37.8% in large municipalities (≥125 000 residents; PR=7.6). CONCLUSION: The prevalence of Vision Zero plans and strategies across the USA is low. Additional adoption of Vision Zero plans and strategies could help address traffic fatalities.
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Acidentes de Trânsito , Condução de Veículo , Humanos , Estudos Transversais , Estados Unidos/epidemiologia , Acidentes de Trânsito/estatística & dados numéricos , Acidentes de Trânsito/prevenção & controle , Condução de Veículo/estatística & dados numéricos , Prevalência , Inquéritos e QuestionáriosRESUMO
Naked carp (Gymnocypris przewalskii) is the only fish species commercially harvested in Qinghai Lake, which is the largest inland saltwater lake in China. Multiple ecological stresses such as long-term overfishing, drying-up of riverine inflows, and decreases in spawning habitat caused the naked carp population to decrease from 320,000 tons before the 1950s to only 3000 tons by the early 2000s. We used matrix projection population modeling to quantitatively simulate the dynamics of the naked carp population from the 1950s to the 2020s. Five versions of the matrix model were developed from the field and laboratory information that represented different population states (high but declining, low abundance, very low abundance, initial recovery, pristine). Equilibrium analysis was applied to density-independent versions of the matrices and population growth rate, age composition, and elasticities were compared among versions. Stochastic, density-dependent version of the most recent decade (recovering) version was used to simulate the time-dependent responses to a range of levels of artificial reproduction (addition of age-1 from hatchery) and of the pristine version to simulate combinations of fishing rate and minimum age of harvest. Results showed the major role of overfishing in the population decline and that the population growth rate was most sensitive to the survival of juveniles and the spawning success of early-age adults. Dynamic simulations showed a rapid population response to artificial reproduction when population abundance was low and that if artificial reproduction continues at its current level, then population biomass would reach 75% of its pristine biomass after 50 years. Simulations with the pristine version identified sustainable fishing levels and the importance of protecting the first few ages of maturity. Overall, modeling results showed that artificial reproduction under conditions of no fishing is an effective approach to restoring the naked carp population. Further effectiveness should consider maximizing survival in the months just after release and maintaining genetic and phenotypic diversity. More information on density-dependent growth, survival, and reproduction, as well as on the genetic diversity and growth and migratory behavior (phenotypic variation) of released and native-spawned fish, would help inform management and conservation strategies and practices going forward.
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Carpas , Animais , Lagos , Conservação dos Recursos Naturais , Pesqueiros , China , Dinâmica PopulacionalRESUMO
Early Eocene primate postcranial bones from the Vastan lignite mine of Gujarat, India, have proven useful for understanding the haplorhine and strepsirrhine divergence. Previous analyses of material assigned to Asiadapidae supported interpretations that these primates were generalized arboreal quadrupeds, while the omomyid Vastanomys was likely to have been more proficient leaper than asiadapids. More recent examinations of long bone cross-sectional properties and calcaneal elongation have complicated the behavioral interpretations of these fossils. This study examines whole talar and calcaneal morphology of the Vastan material to refine the locomotor reconstructions of these fossils. A comparative sample of extant primate species representing various locomotor behaviors was obtained by accessing surface models from MorphoSource.org. Surface models of fossil specimens attributed to Asiadapis cambayensis, Marcgodinotius indicus, and Vastanomys major were generated from micro-computed tomography scans. A morphological analysis was carried out using weighted spherical harmonics, a Fourier-based method that represents surfaces using coefficients associated with a common set of spherical harmonic functions. The coefficients describing each surface were then used as shape variables in a principal components analysis. Significant differences between locomotor groups were assessed using nonparametric tests. Results from extant comparative samples show that locomotor behavior can be predicted from both talar and calcaneal morphology when phylogenetic relationships are known. Consistent with previous analyses, our results indicate that Asiadapis cambayensis and Marcgodinotius indicus were likely arboreal quadrupeds with some leaping capabilities. Vastanomys major is reconstructed as an arboreal quadruped with greater leaping proficiency than its asiadapid counterparts based on its talar morphology.
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Calcâneo , Fósseis , Animais , Calcâneo/anatomia & histologia , Filogenia , Primatas/anatomia & histologia , Microtomografia por Raio-XRESUMO
The early Eocene of the southern Bighorn Basin, Wyoming, is notable for its nearly continuous record of mammalian fossils. Microsyopinae (?Primates) is one of several lineages that shows evidence of evolutionary change associated with an interval referred to as Biohorizon A. Arctodontomys wilsoni is replaced by a larger species, Arctodontomys nuptus, during the biohorizon interval in what is likely an immigration/emigration or immigration/local extinction event. The latter is then superseded by Microsyops angustidens after the end of the Biohorizon A interval. Although this pattern has been understood for some time, denser sampling has led to the identification of a specimen intermediate in morphology between A. nuptus and M. angustidens, located stratigraphically as the latter is appearing. Because specimens of A. nuptus have been recovered approximately 60 m above the appearance of M. angustidens, it is clear that A. nuptus did not suffer pseudoextinction. Instead, evidence suggests that M. angustidens branched off from a population of A. nuptus, but the latter species persisted. This represents possible evidence of cladogenesis, which has rarely been directly documented in the fossil record. The improved understanding of both evolutionary transitions with better sampling highlights the problem of interpreting gaps in the fossil record as punctuations.
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Fósseis , Especiação Genética , Animais , Evolução Biológica , Primatas , WyomingRESUMO
Objectives: Alzheimer's disease (AD) is a growing global health crisis exacerbated by increasing life span and an aging demographic. Convergent lines of evidence, including genome-wide association studies, strongly implicate neuroinflammation in the pathogenesis of AD. Several dietary agents, including phenolic-rich foods, show promise for the prevention and/or management of AD, which in large part, has been attributed to their anti-inflammatory effects. We previously reported that a food-grade phenolic-enriched maple syrup extract (MSX) inhibited neuroinflammation in vitro but whether these effects are translatable in vivo remain unknown. Herein, we assessed MSX's ability to attenuate early neuroinflammation in a transgenic mouse model of AD.Methods: The effects of MSX on AD-related neuroinflammation was evaluated by orally administering MSX (100 and 200 mg/kg/day for 30 days) to the 3xTg-AD mouse model of AD. The expression of inflammatory markers in mouse brains were analyzed with LC-MS/MS with SWATH acquisition.Results: 3xTg-AD mice dosed orally with MSX have decreased expression of several inflammatory proteins, including, most notably, the AD risk-associated protein 'triggering receptor expressed on myeloid cells-2' (TREM2), and stimulator of interferon genes TMEM173, and suppressor of cytokine signaling-6 (SOCS6). However, this decrease in inflammation did not coincide with a decrease in pathogenic amyloid generation or lipid peroxidation.Discussion: These data demonstrate that oral administration of this maple syrup derived natural product reduces key neuroinflammatory indices of AD in the 3xTg-AD model of AD. Therefore, further studies to investigate MSX's potential as a dietary intervention strategy for AD prevention and/or management are warranted.
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Acer , Doença de Alzheimer , Anti-Inflamatórios/administração & dosagem , Doenças Neuroinflamatórias/tratamento farmacológico , Fenóis/administração & dosagem , Extratos Vegetais/administração & dosagem , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/análise , Animais , Química Encefálica , Modelos Animais de Doenças , Feminino , Espectrometria de Massas , Glicoproteínas de Membrana/análise , Camundongos , Camundongos Transgênicos , Doenças Neuroinflamatórias/metabolismo , Fitoterapia , Receptores Imunológicos/análiseRESUMO
The Chesapeake Bay is the largest, most productive, and most biologically diverse estuary in the continental United States providing crucial habitat and natural resources for culturally and economically important species. Pressures from human population growth and associated development and agricultural intensification have led to excessive nutrient and sediment inputs entering the Bay, negatively affecting the health of the Bay ecosystem and the economic services it provides. The Chesapeake Bay Program (CBP) is a unique program formally created in 1983 as a multi-stakeholder partnership to guide and foster restoration of the Chesapeake Bay and its watershed. Since its inception, the CBP Partnership has been developing, updating, and applying a complex linked modeling system of watershed, airshed, and estuary models as a planning tool to inform strategic management decisions and Bay restoration efforts. This paper provides a description of the 2017 CBP Modeling System and the higher trophic level models developed by the NOAA Chesapeake Bay Office, along with specific recommendations that emerged from a 2018 workshop designed to inform future model development. Recommendations highlight the need for simulation of watershed inputs, conditions, processes, and practices at higher resolution to provide improved information to guide local nutrient and sediment management plans. More explicit and extensive modeling of connectivity between watershed landforms and estuary sub-areas, estuarine hydrodynamics, watershed and estuarine water quality, the estuarine-watershed socioecological system, and living resources will be important to broaden and improve characterization of responses to targeted nutrient and sediment load reductions. Finally, the value and importance of maintaining effective collaborations among jurisdictional managers, scientists, modelers, support staff, and stakeholder communities is emphasized. An open collaborative and transparent process has been a key element of successes to date and is vitally important as the CBP Partnership moves forward with modeling system improvements that help stakeholders evolve new knowledge, improve management strategies, and better communicate outcomes.
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SIGNIFICANCE: One-year follow-up is recommended for patients with macular diseases to assess functional changes associated with disease progression and to modify low-vision (LV) treatment plans, if indicated. PURPOSE: The purpose of this study was to observe 255 patients with macular diseases who received LV rehabilitation (rehabilitation with a therapist) or basic LV services (LV devices dispensed without therapy) during Veterans Affairs Low-vision Intervention Trial II after the trial ended at 4 months until 1-year follow-up. METHODS: The primary outcome measure was visual ability measured with the 48-item Veterans Affairs Low-vision Visual Functioning Questionnaire. Mean visual ability scores for the treatment groups were compared from baseline to 4 months, 4 months to 1 year, and baseline to 1 year. Changes from baseline to 1 year were compared between the two groups. Predictors of changes in visual ability from 4 months to 1 year were assessed using linear regression. RESULTS: Both groups experienced significant improvement in all measures of visual ability from baseline to 1 year but lost visual reading ability during the observation period (LV rehabilitation group, -0.64 [1.2] logit; 95% confidence interval [CI], -0.84 to -0.44 logit; basic LV group, -0.63 [1.4] logit; 95% CI, -0.88 to -0.38 logit), and overall visual ability was lost in the LV rehabilitation group (-0.20 [0.8] logit; 95% CI, -0.34 to -0.06 logit). Loss of visual reading ability in both groups from 4 months to 1 year was predicted by reading ability scores at 4 months, loss of near visual acuity from 4 months to 1 year, and lower EuroQol-5D utility index scores; loss of overall visual ability in the LV rehabilitation group during the same time period was predicted by lower overall ability scores at 4 months. CONCLUSIONS: Visual ability significantly improved in all groups from baseline to 1 year. However, the loss of visual reading ability experienced by both groups from 4 months to 1 year reduced the benefit of the services provided.
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Doenças Retinianas/reabilitação , Veteranos/estatística & dados numéricos , Baixa Visão/reabilitação , Pessoas com Deficiência Visual/reabilitação , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Centros de Reabilitação , Doenças Retinianas/fisiopatologia , Perfil de Impacto da Doença , Inquéritos e Questionários , Resultado do Tratamento , Estados Unidos , United States Department of Veterans Affairs , Baixa Visão/fisiopatologia , Acuidade Visual/fisiologiaRESUMO
Several new fossil specimens from the Cambay Shale Formation at Tadkeshwar Lignite Mine in Gujarat document the presence of two previously unknown early Eocene primate species from India. A new species of Asiadapis is named based on a jaw fragment preserving premolars similar in morphology to those of A. cambayensis but substantially larger. Also described is an exceptionally preserved edentulous dentary (designated cf. Asiadapis, unnamed sp. nov.) that is slightly larger and much more robust than previously known Cambay Shale primates. Its anatomy most closely resembles that of Eocene adapoids, and the dental formula is the same as in A. cambayensis. A femur and calcaneus are tentatively allocated to the same taxon. Although the dentition is unknown, exquisite preservation of the dentary of cf. Asiadapis sp. nov. enables an assessment of masticatory musculature, function, and gape adaptations, as well as comparison with an equally well-preserved dentary of the asiadapid Marcgodinotius indicus, also from Tadkeshwar. The new M. indicus specimen shows significant gape adaptations but was probably capable of only weak bite force, whereas cf. Asiadapis sp. nov. probably used relatively smaller gapes but could generate relatively greater bite forces.
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Fósseis/anatomia & histologia , Primatas/classificação , Animais , Biodiversidade , Índia , Primatas/anatomia & histologiaRESUMO
Quantifying the impacts of disturbances such as oil spills on marine species can be challenging. Natural environmental variability, human responses to the disturbance (e.g., fisheries closures), the complex life histories of the species being monitored, and limited pre-spill data can make detection of effects of oil spills difficult. Using long-term monitoring data from the state of Louisiana (USA), we applied novel spatiotemporal approaches to identify anomalies in species occurrence and catch rates. We included covariates (salinity, temperature, turbidity) to help isolate unusual events. While some species showed evidence of unlikely temporal anomalies in occurrence or catch rates, we found that the majority of the observed anomalies were also before the Deepwater Horizon event. Several species-gear combinations suggested upticks in the spatial variability immediately following the spill, but most species indicated no trend. Across species-gear combinations, there was no clear evidence for synchronous or asynchronous responses in occurrence or catch rates across sites following the spill. Our results are in general agreement to other analyses of monitoring data that detected small impacts, but in contrast to recent results from ecological modeling that showed much larger effects of the oil spill on fish and shellfish.
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Pesqueiros/estatística & dados numéricos , Peixes/fisiologia , Poluição por Petróleo/análise , Poluentes Químicos da Água/análise , Animais , Monitoramento Ambiental , Golfo do México , Humanos , Louisiana , Alimentos Marinhos/análise , Análise Espaço-Temporal , Poluição Química da Água/estatística & dados numéricosRESUMO
The oldest primates of modern aspect (euprimates) appear abruptly on the Holarctic continents during a brief episode of global warming known as the Paleocene-Eocene Thermal Maximum, at the beginning of the Eocene (â¼56 Ma). When they first appear in the fossil record, they are already divided into two distinct clades, Adapoidea (basal members of Strepsirrhini, which includes extant lemurs, lorises, and bushbabies) and Omomyidae (basal Haplorhini, which comprises living tarsiers, monkeys, and apes). Both groups have recently been discovered in the early Eocene Cambay Shale Formation of Vastan lignite mine, Gujarat, India, where they are known mainly from teeth and jaws. The Vastan fossils are dated at â¼54.5 Myr based on associated dinoflagellates and isotope stratigraphy. Here, we describe new, exquisitely preserved limb bones of these Indian primates that reveal more primitive postcranial characteristics than have been previously documented for either clade, and differences between them are so minor that in many cases we cannot be certain to which group they belong. Nevertheless, the small distinctions observed in some elements foreshadow postcranial traits that distinguish the groups by the middle Eocene, suggesting that the Vastan primates-though slightly younger than the oldest known euprimates-may represent the most primitive known remnants of the divergence between the two great primate clades.
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Fósseis , Haplorrinos/anatomia & histologia , Strepsirhini/anatomia & histologia , Animais , Osso e Ossos/anatomia & histologia , Extremidades/anatomia & histologia , Especiação Genética , Haplorrinos/classificação , Índia , Strepsirhini/classificaçãoRESUMO
Individuals are commonly exposed to fluctuating levels of stressors, while most laboratory experiments focus on constant exposures. We develop and test a mathematical model for predicting the effects of low dissolved oxygen (hypoxia) on growth, reproduction, and survival using laboratory experiments on fish and shrimp. The exposure-effects model simulates the hourly reductions in growth and survival, and the reduction in reproduction (fecundity) at times of spawning, of an individual as it is exposed to constant or hourly fluctuating dissolved oxygen (DO) concentrations. The model was applied to seven experiments involving fish and shrimp that included constant and fluctuating DO exposures, with constant exposures used for parameter estimation and the model then used to simulate the growth, reproduction, and survival in the fluctuating treatments. Cumulative effects on growth, reproduction, and survival were predicted well by the model, but the model did not replay the observed episodic low survival days. Further investigation should involve the role of acclimation, possible inclusion of repair effects in reproduction and survival, and the sensitivity of model predictions to the shape of the immediate effects function. Additional testing of the model with other taxa, different patterns of fluctuating exposures, and different stressors is needed to determine the model's generality and robustness.
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Simulação por Computador , Decápodes/crescimento & desenvolvimento , Peixes/crescimento & desenvolvimento , Modelos Biológicos , Oxigênio/farmacologia , Reprodução/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Calibragem , Decápodes/efeitos dos fármacos , Fertilidade/efeitos dos fármacos , Solubilidade , Análise de SobrevidaRESUMO
The earliest euprimates to arrive in North America were larger-bodied notharctids and smaller-bodied omomyids. Through the Eocene, notharctids generally continued to increase in body size, whereas omomyids generally radiated within small- and increasingly mid-sized niches in the middle Eocene. This study examines the influence of changing body size and diet on the evolution of the lower fourth premolar in Eocene euprimates. The P4 displays considerable morphological variability in these taxa. Despite the fact that most studies of primate dental morphology have focused on the molars, P4 can also provide important paleoecological insights. We analyzed the P4 from 177 euprimate specimens, representing 35 species (11 notharctids and 24 omomyids), in three time bins of approximately equal duration: early Wasatchian, late Wasatchian, and Bridgerian. Two-dimensional surface landmarks were collected from lingual photographs, capturing important variation in cusp position and tooth shape. Disparity metrics were calculated and compared for the three time bins. In the early Eocene, notharctids have a more molarized P4 than omomyids. During the Bridgerian, expanding body size range of omomyids was accompanied by a significant increase in P4 disparity and convergent evolution of the semimolariform condition in the largest omomyines. P4 morphology relates to diet in early euprimates, although patterns vary between families.
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Evolução Biológica , Fósseis , Primatas/anatomia & histologia , Dente/anatomia & histologia , Animais , Antropologia Física , Tamanho Corporal , Dieta , Odontometria , Análise de Componente Principal , WyomingRESUMO
Over the past decade, human genome-wide association and expression studies have strongly implicated dysregulation of the innate immune system in the pathogenesis of Alzheimer's disease (AD). Single cell mRNA sequencing studies have identified innate immune cell subtypes that are minimally present in normal healthy brain, but whose numbers greatly increase in association with AD pathology. These AD pathology-associated immune cells are putatively the locus for the immune-related AD risk. While the prevailing view is that these immune cells arise from transformation of resident brain microglia, studies across several decades and using multiple techniques and strategies suggest instead that the pathology-associated immune cells are bone-marrow derived hematopoietic cells that are recruited into brain. We critically review this translational literature, emphasizing the strengths and limitations of techniques used to address recruitment and the experimental designs employed. We conclude that the aggregate evidence points toward recruitment into brain of innate immune cells of the myeloid dendritic cell lineage. Recruitment of dendritic cells and their role in AD pathogenesis has broad implications for our understanding of the etiology and pathobiology of AD that impact the strategies to develop new, immune system-targeted therapeutics for this devastating disease.
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INTRODUCTION: Obesity and physical inactivity are considered possible U.S. national security threats because of their impact on military recruitment. The objectives of this study were to estimate the prevalence of (1) BMI eligibility for military entrance, (2) adequate physical activity participation among the BMI-eligible population, and (3) combined BMI eligibility and adequate physical activity. METHODS: This cross-sectional study of nonpregnant, military-aged civilians (aged 17-42 years) used objectively measured weight and height data and self-reported aerobic physical activity data from the 2015-2020 National Health and Nutrition Examination Survey. BMI eligibility was defined as 19.0-27.5 kg/m2, per Department of Defense regulation. Adequate physical activity for entering initial military training was defined as ≥300 minutes/week of equivalent moderate-intensity aerobic physical activity from all domains, approximating U.S. Army guidance. Participants meeting both definitions were further classified as eligible and active. Analyses were conducted in 2021-2022. RESULTS: Of military-aged participants (unweighted n=5,964), 47.3% were eligible by BMI. Among BMI-eligible participants, 72.5% reported adequate physical activity. Taken together, 34.3% were both eligible and active. The prevalence of eligible and active status was higher among males, persons who were younger and non-Hispanic White, college graduates, and those with higher family income than among their counterparts. CONCLUSIONS: Among the military-aged U.S. population, slightly under half were eligible to enter the military on the basis of their BMI, and only 1 in 3 met BMI eligibility and were adequately physically active. Equitable promotion of healthy weight achievement and physical activity participation may improve military preparedness.
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Militares , Masculino , Humanos , Estados Unidos , Índice de Massa Corporal , Estudos Transversais , Inquéritos Nutricionais , Exercício FísicoRESUMO
Tau is a multiply phosphorylated protein that is essential for the development and maintenance of the nervous system. Errors in Tau action are associated with Alzheimer disease and related dementias. A huge literature has led to the widely held notion that aberrant Tau hyperphosphorylation is central to these disorders. Unfortunately, our mechanistic understanding of the functional effects of combinatorial Tau phosphorylation remains minimal. Here, we generated four singly pseudophosphorylated Tau proteins (at Thr(231), Ser(262), Ser(396), and Ser(404)) and four doubly pseudophosphorylated Tau proteins using the same sites. Each Tau preparation was assayed for its abilities to promote microtubule assembly and to regulate microtubule dynamic instability in vitro. All four singly pseudophosphorylated Tau proteins exhibited loss-of-function effects. In marked contrast to the expectation that doubly pseudophosphorylated Tau would be less functional than either of its corresponding singly pseudophosphorylated forms, all of the doubly pseudophosphorylated Tau proteins possessed enhanced microtubule assembly activity and were more potent at regulating dynamic instability than their compromised singly pseudophosphorylated counterparts. Thus, the effects of multiple pseudophosphorylations were not simply the sum of the effects of the constituent single pseudophosphorylations; rather, they were generally opposite to the effects of singly pseudophosphorylated Tau. Further, despite being pseudophosphorylated at different sites, the four singly pseduophosphorylated Tau proteins often functioned similarly, as did the four doubly pseudophosphorylated proteins. These data lead us to reassess the conventional view of combinatorial phosphorylation in normal and pathological Tau action. They may also be relevant to the issue of combinatorial phosphorylation as a general regulatory mechanism.
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Regulação da Expressão Gênica , Microtúbulos/metabolismo , Proteínas tau/química , Doença de Alzheimer/metabolismo , Citoesqueleto/metabolismo , DNA Complementar/metabolismo , Relação Dose-Resposta a Droga , Humanos , Modelos Biológicos , Paclitaxel/farmacologia , Fosforilação , Ligação Proteica , Isoformas de Proteínas , Estrutura Terciária de ProteínaRESUMO
Adaptive prediction is an important tool for efficient compression of non-stationary signals. A common approach to achieve adaptivity is to switch between a set of prediction modes, designed to capture variations in signal statistics. The design poses several challenges including: i) catastrophic instability due to statistical mismatch driven by propagation through the prediction loop, and ii) severe non-convexity of the cost surface that is often riddled with poor local minima. Motivated by these challenges, this paper presents a near-optimal method for designing prediction modes for adaptive compression. The proposed method builds on a stable, open-loop platform, but with a subterfuge that ensures that the design is asymptotically optimized for closed-loop operation. The non-convexity is handled by deterministic annealing, a powerful optimization tool to avoid poor local minima. To demonstrate the impact of the proposed approach on practical applications, we consider adaptive, transform-domain predictor design for enhancing standard video coding. Experimental results validate the benefits of the proposed design in terms of significant performance gains for both predictive compression systems in general and video coding in particular.
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Spherical video coding is critical to the success of many virtual reality and related applications. This paper focuses on an important class of spherical videos whose dynamics involve camera motion. A common approach to spherical video coding is to project from the sphere onto a plane (or planes), where a standard video coder is applied. The projection induces warping resulting in complex non-linear motion in the projected domain that severely comprises the performance of motion models in standard coders. To overcome this shortcoming, we propose a new motion model that captures the motion field on the sphere, and capitalizes on insights into the perceived motion on the sphere due to camera translation. Specifically, surrounding static points are perceived as moving along their respective geodesics, which all intersect at the points where the camera velocity vector intersects the sphere. We analyze the rate of translation along geodesics and its dependence on the elevation of a pixel on the sphere with respect to the camera velocity vector. The analysis leads to a motion vector modulation scheme that perfectly captures the perceived motion of each pixel. Complementary to the new motion model, we propose a search grid tailored to capture expected geodesic motion on the sphere for effective motion estimation. The proposed method yields significant bit-rate savings over employing standard HEVC after projection, which validates its efficacy.
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The blind troglobite cavefish Sinocyclocheilus rhinocerous lives in oligotrophic, phreatic subterranean waters and possesses a unique cranial morphology including a pronounced supra-occipital horn. We used a combined approach of laboratory observations and Computational Fluid Dynamics modeling to characterize the swimming behavior and other hydrodynamic aspects, i.e., drag coefficients and lateral line sensing distance of S. rhinocerous. Motion capture and tracking based on an Artificial Neural Network, complemented by a Particle Image Velocimetry system to map out water velocity fields, were utilized to analyze the motion of a live specimen in a laboratory aquarium. Computational Fluid Dynamics simulations on flow fields and pressure fields, based on digital models of S. rhinocerous, were also performed. These simulations were compared to analogous simulations employing models of the sympatric, large-eyed troglophile cavefish S. angustiporus. Features of the cavefish swimming behavior deduced from the both live-specimen experiments and simulations included average swimming velocities and three dimensional trajectories, estimates for drag coefficients and potential lateral line sensing distances, and mapping of the flow field around the fish. As expected, typical S. rhinocerous swimming speeds were relatively slow. The lateral line sensing distance was approximately 0.25 body lengths, which may explain the observation that specimen introduced to a new environment tend to swim parallel and near to the walls. Three-dimensional simulations demonstrate that just upstream from the region under the supra-occipital horn the equipotential of the water pressure and velocity fields are nearly vertical. Results support the hypothesis that the conspicuous cranial horn of S. rhinocerous may lead to greater stimulus of the lateral line compared to fish that do not possess such morphology.