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1.
Lancet ; 401(10393): 2060-2071, 2023 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-37290458

RESUMO

BACKGROUND: Assessments of disease burden are important to inform national, regional, and global strategies and to guide investment. We aimed to estimate the drinking water, sanitation, and hygiene (WASH)-attributable burden of disease for diarrhoea, acute respiratory infections, undernutrition, and soil-transmitted helminthiasis, using the WASH service levels used to monitor the UN Sustainable Development Goals (SDGs) as counterfactual minimum risk-exposure levels. METHODS: We assessed the WASH-attributable disease burden of the four health outcomes overall and disaggregated by region, age, and sex for the year 2019. We calculated WASH-attributable fractions of diarrhoea and acute respiratory infections by country using modelled WASH exposures and exposure-response relationships from two updated meta-analyses. We used the WHO and UNICEF Joint Monitoring Programme for Water Supply, Sanitation and Hygiene public database to estimate population exposure to different WASH service levels. WASH-attributable undernutrition was estimated by combining the population attributable fractions (PAF) of diarrhoea caused by unsafe WASH and the PAF of undernutrition caused by diarrhoea. Soil-transmitted helminthiasis was fully attributed to unsafe WASH. FINDINGS: We estimate that 1·4 (95% CI 1·3-1·5) million deaths and 74 (68-80) million disability-adjusted life-years (DALYs) could have been prevented by safe WASH in 2019 across the four designated outcomes, representing 2·5% of global deaths and 2·9% of global DALYs from all causes. The proportion of diarrhoea that is attributable to unsafe WASH is 0·69 (0·65-0·72), 0·14 (0·13-0·17) for acute respiratory infections, and 0·10 (0·09-0·10) for undernutrition, and we assume that the entire disease burden from soil-transmitted helminthiasis was attributable to unsafe WASH. INTERPRETATION: WASH-attributable burden of disease estimates based on the levels of service established under the SDG framework show that progress towards the internationally agreed goal of safely managed WASH services for all would yield major public-health returns. FUNDING: WHO and Foreign, Commonwealth & Development Office.


Assuntos
Água Potável , Helmintíase , Desnutrição , Infecções Respiratórias , Humanos , Saneamento , Higiene , Helmintíase/epidemiologia , Desnutrição/epidemiologia , Efeitos Psicossociais da Doença , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/etiologia , Diarreia/epidemiologia , Diarreia/etiologia , Avaliação de Resultados em Cuidados de Saúde , Saúde Global , Carga Global da Doença
2.
Curr Allergy Asthma Rep ; 24(7): 381-393, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38878250

RESUMO

PURPOSE OF REVIEW: To discuss the effectiveness of biologics, some of which comprise the newest class of asthma controller medications, and non-biologics in the treatment of asthma co-existing with obesity. RECENT FINDINGS: Our review of recent preliminary and published data from clinical trials revealed that obese asthmatics respond favorably to dupilumab, mepolizumab, omalizumab, and tezepelumab, which are biologics currently indicated as add-on maintenance therapy for severe asthma. Furthermore, clinical trials are ongoing to assess the efficacy of non-biologics in the treatment of obese asthma, including a glucagon-like peptide-1 receptor agonist, a Janus kinase inhibitor, and probiotics. Although many biologics presently indicated as add-on maintenance therapy for severe asthma exhibit efficacy in obese asthmatics, other phenotypes of asthma co-existing with obesity may be refractory to these medications. Thus, to improve quality of life and asthma control, it is imperative to identify therapeutic options for all existing phenotypes of obese asthma.


Assuntos
Antiasmáticos , Asma , Produtos Biológicos , Obesidade , Asma/tratamento farmacológico , Asma/complicações , Humanos , Obesidade/complicações , Obesidade/tratamento farmacológico , Antiasmáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Probióticos/uso terapêutico
3.
Retina ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39024646

RESUMO

PURPOSE: We describe three different approaches for lens management in cases of metallic IOFBs involving the posterior segment. METHODS: All consecutive posterior segment metallic IOFB cases from 2012 to 2023 at a single institution were included in this retrospective case series. Surgical outcomes and surgical videos are presented. RESULTS: A total of 25 metallic IOFB cases were included. In 9 cases, there was no significant lens involvement, therefore not requiring lens extraction at the time of IOFB removal. In 8 cases with traumatic cataract, lens extraction sparing the anterior lens capsule was performed with IOFB removal. In 8 cases, both lens extraction and lens capsule removal were required at the time of IOFB removal. CONCLUSION: We demonstrate our algorithm to capsular management in patients who present with IOFB with good visual outcomes in follow-up.

4.
Lancet ; 400(10345): 48-59, 2022 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-35780792

RESUMO

BACKGROUND: Estimates of the effectiveness of water, sanitation, and hygiene (WASH) interventions that provide high levels of service on childhood diarrhoea are scarce. We aimed to provide up-to-date estimates on the burden of disease attributable to WASH and on the effects of different types of WASH interventions on childhood diarrhoea in low-income and middle-income countries (LMICs). METHODS: In this systematic review and meta-analysis, we updated previous reviews following their search strategy by searching MEDLINE, Embase, Scopus, Cochrane Library, and BIOSIS Citation Index for studies of basic WASH interventions and of WASH interventions providing a high level of service, published between Jan 1, 2016, and May 25, 2021. We included randomised and non-randomised controlled trials conducted at household or community level that matched exposure categories of the so-called service ladder approach of the Sustainable Development Goal (SDG) for WASH. Two reviewers independently extracted study-level data and assessed risk of bias using a modified Newcastle-Ottawa Scale and certainty of evidence using a modified Grading of Recommendations, Assessment, Development, and Evaluation approach. We analysed extracted relative risks (RRs) and 95% CIs using random-effects meta-analyses and meta-regression models. This study is registered with PROSPERO, CRD42016043164. FINDINGS: 19 837 records were identified from the search, of which 124 studies were included, providing 83 water (62 616 children), 20 sanitation (40 799 children), and 41 hygiene (98 416 children) comparisons. Compared with untreated water from an unimproved source, risk of diarrhoea was reduced by up to 50% with water treated at point of use (POU): filtration (n=23 studies; RR 0·50 [95% CI 0·41-0·60]), solar treatment (n=13; 0·63 [0·50-0·80]), and chlorination (n=25; 0·66 [0·56-0·77]). Compared with an unimproved source, provision of an improved drinking water supply on premises with higher water quality reduced diarrhoea risk by 52% (n=2; 0·48 [0·26-0·87]). Overall, sanitation interventions reduced diarrhoea risk by 24% (0·76 [0·61-0·94]). Compared with unimproved sanitation, providing sewer connection reduced diarrhoea risk by 47% (n=5; 0·53 [0·30-0·93]). Promotion of handwashing with soap reduced diarrhoea risk by 30% (0·70 [0·64-0·76]). INTERPRETATION: WASH interventions reduced risk of diarrhoea in children in LMICs. Interventions supplying either water filtered at POU, higher water quality from an improved source on premises, or basic sanitation services with sewer connection were associated with increased reductions. Our results support higher service levels called for under SDG 6. Notably, no studies evaluated interventions that delivered access to safely managed WASH services, the level of service to which universal coverage by 2030 is committed under the SDG. FUNDING: WHO, Foreign, Commonwealth & Development Office, and National Institute of Environmental Health Sciences.


Assuntos
Água Potável , Saneamento , Criança , Diarreia/epidemiologia , Diarreia/prevenção & controle , Desinfecção das Mãos , Humanos , Sabões
5.
Proc Biol Sci ; 290(2000): 20230355, 2023 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-37312549

RESUMO

Many social insects display age polyethism: young workers stay inside the nest, and only older workers forage. This behavioural transition is accompanied by genetic and physiological changes, but the mechanistic origin of it remains unclear. To investigate if the mechanical demands on the musculoskeletal system effectively prevent young workers from foraging, we studied the biomechanical development of the bite apparatus in Atta vollenweideri leaf-cutter ants. Fully matured foragers generated peak in vivo bite forces of around 100 mN, more than one order of magnitude in excess of those measured for freshly eclosed callows of the same size. This change in bite force was accompanied by a sixfold increase in the volume of the mandible closer muscle, and by a substantial increase of the flexural rigidity of the head capsule, driven by a significant increase in both average thickness and indentation modulus of the head capsule cuticle. Consequently, callows lack the muscle force capacity required for leaf-cutting, and their head capsule is so compliant that large muscle forces would be likely to cause damaging deformations. On the basis of these results, we speculate that continued biomechanical development post eclosion may be a key factor underlying age polyethism, wherever foraging is associated with substantial mechanical demands.


Assuntos
Formigas , Gastrópodes , Animais , Fenômenos Biomecânicos , Músculos , Força de Mordida
6.
Cereb Cortex ; 32(15): 3331-3346, 2022 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34963140

RESUMO

Decades of research have shown that global brain states such as arousal can be indexed by measuring the properties of the eyes. The spiking responses of neurons throughout the brain have been associated with the pupil, small fixational saccades, and vigor in eye movements, but it has been difficult to isolate how internal states affect the eyes, and vice versa. While recording from populations of neurons in the visual and prefrontal cortex (PFC), we recently identified a latent dimension of neural activity called "slow drift," which appears to reflect a shift in a global brain state. Here, we asked if slow drift is correlated with the action of the eyes in distinct behavioral tasks. We recorded from visual cortex (V4) while monkeys performed a change detection task, and PFC, while they performed a memory-guided saccade task. In both tasks, slow drift was associated with the size of the pupil and the microsaccade rate, two external indicators of the internal state of the animal. These results show that metrics related to the action of the eyes are associated with a dominant and task-independent mode of neural activity that can be accessed in the population activity of neurons across the cortex.


Assuntos
Movimentos Sacádicos , Córtex Visual , Animais , Cognição , Neurônios/fisiologia , Pupila , Córtex Visual/fisiologia
7.
Am J Physiol Regul Integr Comp Physiol ; 323(6): R921-R934, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36283092

RESUMO

Interleukin (IL)-11, a multifunctional cytokine, contributes to numerous biological processes, including adipogenesis, hematopoiesis, and inflammation. Asthma, a respiratory disease, is notably characterized by reversible airway obstruction, persistent lung inflammation, and airway hyperresponsiveness (AHR). Nasal insufflation of IL-11 causes AHR in wild-type mice while lung inflammation induced by antigen sensitization and challenge, which mimics features of atopic asthma in humans, is attenuated in mice genetically deficient in IL-11 receptor subunit α-1 (IL-11Rα1-deficient mice), a transmembrane receptor that is required conjointly with glycoprotein 130 to transduce IL-11 signaling. Nevertheless, the contribution of IL-11Rα1 to characteristics of nonatopic asthma is unknown. Thus, based on the aforementioned observations, we hypothesized that genetic deficiency of IL-11Rα1 attenuates lung inflammation and increases airway responsiveness after acute inhalation exposure to ozone (O3), a criteria pollutant and nonatopic asthma stimulus. Accordingly, 4 and/or 24 h after cessation of exposure to filtered room air or O3, we assessed lung inflammation and airway responsiveness in wild-type and IL-11Rα1-deficient mice. With the exception of bronchoalveolar lavage macrophages and adiponectin, which were significantly increased and decreased, respectively, in O3-exposed IL-11Rα1-deficient as compared with O3-exposed wild-type mice, no other genotype-related differences in lung inflammation indices that we quantified were observed in O3-exposed mice. However, airway responsiveness to acetyl-ß-methylcholine chloride (methacholine) was significantly diminished in IL-11Rα1-deficient as compared with wild-type mice after O3 exposure. In conclusion, these results demonstrate that IL-11Rα1 minimally contributes to lung inflammation but is required for maximal airway responsiveness to methacholine in a mouse model of nonatopic asthma.


Assuntos
Asma , Ozônio , Pneumonia , Humanos , Camundongos , Animais , Cloreto de Metacolina/efeitos adversos , Ozônio/toxicidade , Interleucina-11/efeitos adversos , Asma/genética , Pneumonia/induzido quimicamente , Pneumonia/genética , Pneumonia/complicações , Receptores de Interleucina-11 , Líquido da Lavagem Broncoalveolar
8.
Br J Sports Med ; 56(22): 1307-1319, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36150753

RESUMO

OBJECTIVE: To evaluate the effectiveness of interventions to prevent and manage knee injuries in runners. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Web of Science and SPORTDiscus up to May 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials (RCTs) with a primary aim of evaluating the effectiveness of intervention(s) to prevent or manage running-related knee injury. RESULTS: Thirty RCTs (18 prevention, 12 management) analysed multiple interventions in novice and recreational running populations. Low-certainty evidence (one trial, 320 participants) indicated that running technique retraining (to land softer) reduced the risk of knee injury compared with control treadmill running (risk ratio (RR) 0.32, 95% CI 0.16 to 0.63). Very low-certainty to low-certainty evidence from 17 other prevention trials (participant range: 24 -3287) indicated that various footwear options, multicomponent exercise therapy, graduated running programmes and online and in person injury prevention education programmes did not influence knee injury risk (RR range: 0.55-1.06). In runners with patellofemoral pain, very low-certainty to low-certainty evidence indicated that running technique retraining strategies, medial-wedged foot orthoses, multicomponent exercise therapy and osteopathic manipulation can reduce knee pain in the short-term (standardised mean difference range: -4.96 to -0.90). CONCLUSION: There is low-certainty evidence that running technique retraining to land softer may reduce knee injury risk by two-thirds. Very low-certainty to low-certainty evidence suggests that running-related patellofemoral pain may be effectively managed through a variety of active (eg, running technique retraining, multicomponent exercise therapy) and passive interventions (eg, foot orthoses, osteopathic manipulation). PROSPERO REGISTRATION NUMBER: CRD42020150630.


Assuntos
Traumatismos do Joelho , Síndrome da Dor Patelofemoral , Corrida , Humanos , Terapia por Exercício , Traumatismos do Joelho/prevenção & controle , Articulação do Joelho , Síndrome da Dor Patelofemoral/terapia , Corrida/lesões , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
J Pediatr ; 220: 49-55.e2, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32061407

RESUMO

OBJECTIVES: To assess the geographic variation of sudden unexpected infant death (SUID) and test if variation in geographic factors, such as state, latitude, and longitude, play a role in SUID risk across the US. STUDY DESIGN: We analyzed the Centers for Disease Control and Prevention's Cohort Linked Birth/Infant Death dataset (2005-2010; 22 882 SUID cases, 25 305 837 live births, rate 0.90/1000). SUID was defined as infant deaths (ages 7-364 days) that included sudden infant death syndrome, ill-defined and unknown cause of mortality, and accidental suffocation and strangulation in bed. SUID geographic variation was analyzed using 2 statistical models, logistic regression and generalized additive model (GAM). RESULTS: Both models produced similar results. Without adjustment, there was marked geographic variation in SUID rates, but the variation decreased after adjusting for covariates including known risk factors for SUID. After adjustment, nine states demonstrated significantly higher or lower SUID mortality than the national average. Geographic contribution to SUID risk in terms of latitude and longitude were also attenuated after adjustment for covariates. CONCLUSION: Understanding why some states have lower SUID rates may enhance SUID prevention strategies.


Assuntos
Morte Súbita do Lactente/epidemiologia , Centers for Disease Control and Prevention, U.S. , Conjuntos de Dados como Assunto , Geografia Médica , Humanos , Lactente , Recém-Nascido , Modelos Estatísticos , Estados Unidos/epidemiologia
10.
BMC Med ; 17(1): 173, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462230

RESUMO

BACKGROUND: Three large new trials of unprecedented scale and cost, which included novel factorial designs, have found no effect of basic water, sanitation and hygiene (WASH) interventions on childhood stunting, and only mixed effects on childhood diarrhea. Arriving at the inception of the United Nations' Sustainable Development Goals, and the bold new target of safely managed water, sanitation and hygiene for all by 2030, these results warrant the attention of researchers, policy-makers and practitioners. MAIN BODY: Here we report the conclusions of an expert meeting convened by the World Health Organization and the Bill and Melinda Gates Foundation to discuss these findings, and present five key consensus messages as a basis for wider discussion and debate in the WASH and nutrition sectors. We judge these trials to have high internal validity, constituting good evidence that these specific interventions had no effect on childhood linear growth, and mixed effects on childhood diarrhea. These results suggest that, in settings such as these, more comprehensive or ambitious WASH interventions may be needed to achieve a major impact on child health. CONCLUSION: These results are important because such basic interventions are often deployed in low-income rural settings with the expectation of improving child health, although this is rarely the sole justification. Our view is that these three new trials do not show that WASH in general cannot influence child linear growth, but they do demonstrate that these specific interventions had no influence in settings where stunting remains an important public health challenge. We support a call for transformative WASH, in so much as it encapsulates the guiding principle that - in any context - a comprehensive package of WASH interventions is needed that is tailored to address the local exposure landscape and enteric disease burden.


Assuntos
Diarreia/etiologia , Transtornos do Crescimento/etiologia , Higiene , Saneamento , Água/efeitos adversos , Criança , Saúde da Criança , Humanos , Pobreza , Saúde Pública/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , População Rural
11.
Arch Toxicol ; 93(8): 2347-2360, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31270586

RESUMO

Indomethacin is a non-steroidal anti-inflammatory drug that causes gastric ulceration and increased 'leakiness' in rat models, and is used routinely as a toxicology assay to screen novel compounds for repair and restitution properties. We set out to establish conditions for indomethacin-induced gut damage in wax-moth (Galleria mellonella) larvae with a view to reducing the need for rodents in such experimentation. We administered indomethacin (0.5-7.5 µg/larva; 2-30 mg/kg) to G. mellonella via intrahaemocoelic injection and gavage (force-feeding) and monitored survival and development, blood cell (haemocyte) numbers, and changes in gut permeability. Increased levels of gut leakiness were observed within the first 4- to 24 h by tracking fluorescent microspheres in the faeces and haemolymph (blood equivalent). Additionally, we recorded varying levels of tissue damage in histological sections of the insect midgut, including epithelial sloughing and cell necrosis. Degeneration of the midgut was accompanied by significant increases in detoxification-associated activities (superoxide dismutase and glutathione-S-transferase). Herein, we present the first evidence that G. mellonella larvae force-fed indomethacin display broad symptoms of gastric damage similar to their rodent counterparts.


Assuntos
Trato Gastrointestinal/efeitos dos fármacos , Indometacina/toxicidade , Mariposas/efeitos dos fármacos , Animais , Trato Gastrointestinal/patologia , Trato Gastrointestinal/fisiologia , Hemócitos/efeitos dos fármacos , Larva/efeitos dos fármacos , Modelos Animais , Permeabilidade , Superóxido Dismutase/metabolismo
14.
Exp Physiol ; 103(12): 1692-1703, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30260066

RESUMO

NEW FINDINGS: What is the central question of this study? When do alterations in pulmonary mechanics occur following chronic low-dose administration of bleomycin? What is the main finding and its importance? Remarkably, we report changes in lung mechanics as early as day 7 that corresponded to parameters determined from single-frequency forced oscillation manoeuvres and pressure-volume loops. These changes preceded substantial histological changes or changes in gene expression levels. These findings are significant to refine drug discovery in idiopathic pulmonary fibrosis, where preclinical studies using lung function parameters would enhance the translational potential of drug candidates where lung function readouts are routinely performed in the clinic. ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is the most widespread form of interstitial lung disease and, currently, there are only limited treatment options available. In preclinical animal models of lung fibrosis, the effectiveness of experimental therapeutics is often deemed successful via reductions in collagen deposition and expression of profibrotic genes in the lung. However, in clinical studies, improvements in lung function are primarily used to gauge the success of therapeutics directed towards IPF. Therefore, we examined whether changes in respiratory system mechanics in the early stages of an experimental model of lung fibrosis can be used to refine drug discovery approaches for IPF. C57BL/6J mice were administered bleomycin (BLM) or a vehicle control i.p. twice a week for 4 weeks. At 7, 14, 21, 28 and 33 days into the BLM treatment regimen, indices of respiratory system mechanics and pressure-volume relationships were measured. Concomitant with these measurements, histological and gene analyses relevant to lung fibrosis were performed. Alterations in respiratory system mechanics and pressure-volume relationships were observed as early as 7 days after the start of BLM administration. Changes in respiratory system mechanics preceded the appearance of histological and molecular indices of lung fibrosis. Administration of BLM leads to early changes in respiratory system mechanics that coincide with the appearance of representative histological and molecular indices of lung fibrosis. Consequently, these data suggest that dampening the early changes in respiratory system mechanics might be used to assess the effectiveness of experimental therapeutics in preclinical animal models of lung fibrosis.


Assuntos
Bleomicina/administração & dosagem , Pulmão/efeitos dos fármacos , Mecânica Respiratória/efeitos dos fármacos , Animais , Líquido da Lavagem Broncoalveolar/citologia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/tratamento farmacológico
15.
Trop Med Int Health ; 23(5): 508-525, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29537671

RESUMO

OBJECTIVES: Safe drinking water, sanitation and hygiene are protective against diarrhoeal disease; a leading cause of child mortality. The main objective was an updated assessment of the impact of unsafe water, sanitation and hygiene (WaSH) on childhood diarrhoeal disease. METHODS: We undertook a systematic review of articles published between 1970 and February 2016. Study results were combined and analysed using meta-analysis and meta-regression. RESULTS: A total of 135 studies met the inclusion criteria. Several water, sanitation and hygiene interventions were associated with lower risk of diarrhoeal morbidity. Point-of-use filter interventions with safe storage reduced diarrhoea risk by 61% (RR = 0.39; 95% CI: 0.32, 0.48); piped water to premises of higher quality and continuous availability by 75% and 36% (RR = 0.25 (0.09, 0.67) and 0.64 (0.42, 0.98)), respectively compared to a baseline of unimproved drinking water; sanitation interventions by 25% (RR = 0.75 (0.63, 0.88)) with evidence for greater reductions when high sanitation coverage is reached; and interventions promoting handwashing with soap by 30% (RR = 0.70 (0.64, 0.77)) vs. no intervention. Results of the analysis of sanitation and hygiene interventions are sensitive to certain differences in study methods and conditions. Correcting for non-blinding would reduce the associations with diarrhoea to some extent. CONCLUSIONS: Although evidence is limited, results suggest that household connections of water supply and higher levels of community coverage for sanitation appear particularly impactful which is in line with targets of the Sustainable Development Goals.


Assuntos
Diarreia/prevenção & controle , Água Potável/normas , Desinfecção das Mãos/normas , Higiene/normas , Abastecimento de Água/normas , Criança , Países em Desenvolvimento , Feminino , Humanos , Masculino , Fatores de Risco , Fatores Socioeconômicos
16.
J Vis ; 17(5): 1, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28460376

RESUMO

A characteristic set of eye movements and fixations are made during reading, so the position of words on the retinae is constantly being updated. Effective decoding of print requires this temporal stream of visual information to be segmented or parsed into its constituent units (e.g., letters or words). Poor readers' difficulties with word recognition could arise at the point of segmenting time-varying visual information, but the mechanisms underlying this process are little understood. Here, we used random-dot displays to explore the effects of reading ability on temporal segmentation. Thirty-eight adult readers viewed test stimuli that were temporally segmented by constraining either local motions or analogous form cues to oscillate back and fourth at each of a range of rates. Participants had to discriminate these segmented patterns from comparison stimuli containing the same motion and form cues but these were temporally intermingled. Results showed that the motion and form tasks could not be performed reliably when segment duration was shorter than a temporal resolution (acuity) limit. The acuity limits for both tasks were significantly and negatively correlated with reading scores. Importantly, the minimum segment duration needed to detect the temporally segmented stimuli was longer in relatively poor readers than relatively good readers. This demonstrates that adult poor readers have difficulty segmenting temporally changing visual input particularly at short segment durations. These results are consistent with evidence suggesting that precise encoding of rapid time-varying information is impaired in developmental dyslexia.


Assuntos
Dislexia/fisiopatologia , Movimentos Oculares/fisiologia , Fixação Ocular/fisiologia , Processos Mentais/fisiologia , Leitura , Feminino , Humanos , Masculino , Fatores de Tempo , Adulto Jovem
17.
FASEB J ; 29(1): 50-60, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25318478

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a lethal, fibroproliferative disease. Pulmonary hypertension (PH) can develop secondary to IPF and increase mortality. Alternatively, activated macrophages (AAMs) contribute to the pathogenesis of both IPF and PH. Here we hypothesized that adenosine signaling through the ADORA2B on AAMs impacts the progression of these disorders and that conditional deletion of ADORA2B on myeloid cells would have a beneficial effect in a model of these diseases. Conditional knockout mice lacking ADORA2B on myeloid cells (Adora2B(f/f)-LysM(Cre)) were exposed to the fibrotic agent bleomycin (BLM; 0.035 U/g body weight, i.p.). At 14, 17, 21, 25, or 33 d after exposure, SpO2, bronchoalveolar lavage fluid (BALF), and histologic analyses were performed. On day 33, lung function and cardiovascular analyses were determined. Markers for AAM and mediators of fibrosis and PH were assessed. Adora2B(f/f)-LysM(Cre) mice presented with attenuated fibrosis, improved lung function, and no evidence of PH compared with control mice exposed to BLM. These findings were accompanied by reduced expression of CD206 and arginase-1, markers for AAMs. A 10-fold reduction in IL-6 and a 5-fold decrease in hyaluronan, both linked to lung fibrosis and PH, were also observed. These data suggest that activation of the ADORA2B on macrophages plays an active role in the pathogenesis of lung fibrosis and PH.


Assuntos
Hipertensão Pulmonar/etiologia , Fibrose Pulmonar Idiopática/etiologia , Receptor A2B de Adenosina/deficiência , Animais , Bleomicina/toxicidade , Modelos Animais de Doenças , Humanos , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/fisiopatologia , Ativação de Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Mieloides/fisiologia , Receptor A2B de Adenosina/genética , Receptor A2B de Adenosina/fisiologia
18.
Brain Cogn ; 108: 20-31, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27429095

RESUMO

Individuals with dyslexia are purported to have a selective dorsal stream impairment that manifests as a deficit in perceiving visual global motion relative to global form. However, the underlying nature of the visual deficit in readers with dyslexia remains unclear. It may be indicative of a difficulty with motion detection, temporal processing, or any task that necessitates integration of local visual information across multiple dimensions (i.e. both across space and over time). To disentangle these possibilities we administered four diagnostic global motion and global form tasks to a large sample of adult readers (N=106) to characterise their perceptual abilities. Two sets of analyses were conducted. First, to investigate if general reading ability is associated with performance on the visual tasks across the entire sample, a composite reading score was calculated and entered into a series of continuous regression analyses. Next, to investigate if the performance of readers with dyslexia differs from that of good readers on the visual tasks we identified a group of forty-three individuals for whom phonological decoding was specifically impaired, consistent with the dyslexic profile, and compared their performance with that of good readers who did not exhibit a phonemic deficit. Both analyses yielded a similar pattern of results. Consistent with previous research, coherence thresholds of poor readers were elevated on a random-dot global motion task and a spatially one-dimensional (1-D) global motion task, but no difference was found on a static global form task. However, our results extend those of previous studies by demonstrating that poor readers exhibited impaired performance on a temporally-defined global form task, a finding that is difficult to reconcile with the dorsal stream vulnerability hypothesis. This suggests that the visual deficit in developmental dyslexia does not reflect an impairment detecting motion per se. It is better characterised as a difficulty processing temporal information, which is exacerbated when local visual cues have to be integrated across multiple (>2) dimensions.


Assuntos
Dislexia/fisiopatologia , Percepção de Movimento/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
19.
J Strength Cond Res ; 30(8): 2129-37, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26808858

RESUMO

Johnston, RJ, Watsford, ML, Austin, D, Pine, MJ, and Spurrs, RW. Movement profiles, match events, and performance in Australian football. J Strength Cond Res 30(8): 2129-2137, 2016-This study examined the relationship between movement demands, match events, and match performance in professional Australian football. Data were collected from 19 players using global positioning system units during 2 Australian Football League seasons. A range of movement demands and instantaneous power measures were collected. The players were divided into high-caliber (HC, ≥17/20) and low-caliber (LC, ≤8/20) groups based on the rating score by their coaches. A Mann-Whitney U-test, independent samples t-test, and effect sizes were used to determine whether any differences existed between the 2 groups. The HC group had a significantly higher match duration (7.2%), higher total distance (9.6%), and covered more distance and spent more time high-speed running per minute (12.7 and 11.9%). Although not significant, the effect sizes revealed that the HC group tended to have a higher mean metabolic power output (2.6%) and spent more time at the high power zone (7.9%). For the match event data, the HC group had significantly more involvements with the football. The results demonstrated the higher physical demands placed on the HC group. The findings suggest that analyzing instantaneous power measures can provide valuable information about the physical demands placed on team sport athletes to coaches and conditioning staff.


Assuntos
Desempenho Atlético/fisiologia , Futebol Americano/fisiologia , Movimento/fisiologia , Adulto , Austrália , Metabolismo Energético/fisiologia , Sistemas de Informação Geográfica , Humanos , Masculino , Estudos Retrospectivos , Corrida/fisiologia , Adulto Jovem
20.
Am J Physiol Lung Cell Mol Physiol ; 309(10): L1174-85, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26386120

RESUMO

Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines-including IL-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], TNF receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1α and IL-1ß)-promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1α, IL-1ß, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin; yet given the aforementioned observations, we hypothesized that murine resistin promotes O3-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indexes of O3-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O3. In wild-type mice, O3 increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O3 increased lung tissue or BALF IL-1α, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient compared with wild-type mice, no genotype-related differences in the other indexes existed following O3 exposure. O3 caused AHR to acetyl-ß-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were nonexistent subsequent to O3 exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O3 exposure but does not promote O3-induced lung pathology.


Assuntos
Poluentes Atmosféricos/toxicidade , Ozônio/toxicidade , Pneumonia/metabolismo , Resistina/genética , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Broncoconstritores/farmacologia , Feminino , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Cloreto de Metacolina/farmacologia , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia/induzido quimicamente , Resistina/sangue
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