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1.
Acta Ophthalmol ; 98(4): e513-e519, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31773899

RESUMO

PURPOSE: To investigate associations between older drivers' perceived vision-related night-driving difficulties and night-time driving performance measured on a closed-road circuit. METHODS: Participants included 26 older drivers (71.8 ± 6.3 years) who reported vision-related night-driving difficulties assessed with the vision and night driving questionnaire (VND-Q). High-contrast, photopic visual acuity (VA) and ratings of discomfort glare (de Boer scale) were also assessed. Night-time driving performance was measured on a closed-road circuit that involved recognition, hazard avoidance and lane-keeping tasks in the absence and presence of intermittent glare. Generalized linear mixed models investigated the relationship between VND-Q scores and overall driving performance scores, as well as with discomfort glare ratings and VA. RESULTS: Greater levels of vision-related night-driving difficulties (VND-Q scores) were significantly associated with poorer night-driving performance (p = 0.003); the association was even stronger for driving performance in the presence of intermittent glare (p = 0.001). Reduced VA was associated with poorer night-driving performance (p = 0.022) but the association was weaker than for the VND-Q scores. In contrast, ratings of discomfort glare were not significantly associated with driving performance (p = 0.14). CONCLUSION: The VND-Q was significantly associated with night-time driving performance and provides a useful instrument for assessing vision-related night-driving difficulties which can be incorporated into clinical vision assessments.


Assuntos
Condução de Veículo , Visão de Cores/fisiologia , Sensibilidades de Contraste/fisiologia , Autorrelato , Transtornos da Visão/epidemiologia , Acuidade Visual , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Transtornos da Visão/fisiopatologia , Testes Visuais
2.
Acta Physiol (Oxf) ; 224(1): e13060, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29489063

RESUMO

AIM: Recent work has demonstrated that activation of the epithelial sodium channel (ENaC) by aberrantly filtered serine proteases causes sodium retention in nephrotic syndrome. The aim of this study was to elucidate a potential role of plasma kallikrein (PKLK) as a candidate serine protease in this context. METHODS: We analysed PKLK in the urine of patients with chronic kidney disease (CKD, n = 171) and investigated its ability to activate human ENaC expressed in Xenopus laevis oocytes. Moreover, we studied sodium retention in PKLK-deficient mice (klkb1-/- ) with experimental nephrotic syndrome induced by doxorubicin injection. RESULTS: In patients with CKD, we found that PKLK is excreted in the urine up to a concentration of 2 µg mL-1 which was correlated with albuminuria (r = .71) and overhydration as assessed by bioimpedance spectroscopy (r = .44). PKLK increased ENaC-mediated whole-cell currents, which was associated with the appearance of a 67 kDa γ-ENaC cleavage product at the cell surface consistent with proteolytic activation. Mutating a putative prostasin cleavage site in γ-ENaC prevented channel stimulation by PKLK. In a mouse model for nephrotic syndrome, active PKLK was present in nephrotic urine of klkb1+/+ but not of klkb1-/- mice. However, klkb1-/- mice were not protected from ENaC activation and sodium retention compared to nephrotic klkb1+/+ mice. CONCLUSION: Plasma kallikrein is detected in the urine of proteinuric patients and mice and activates ENaC in vitro involving the putative prostasin cleavage site. However, PKLK is not essential for volume retention in nephrotic mice.


Assuntos
Canais Epiteliais de Sódio/metabolismo , Rim/enzimologia , Natriurese , Síndrome Nefrótica/enzimologia , Calicreína Plasmática/metabolismo , Equilíbrio Hidroeletrolítico , Adulto , Idoso , Animais , Composição Corporal , Estudos de Casos e Controles , Modelos Animais de Doenças , Doxorrubicina , Canais Epiteliais de Sódio/genética , Feminino , Humanos , Rim/fisiopatologia , Masculino , Potenciais da Membrana , Camundongos Knockout , Pessoa de Meia-Idade , Síndrome Nefrótica/genética , Síndrome Nefrótica/fisiopatologia , Síndrome Nefrótica/urina , Estado de Hidratação do Organismo , Calicreína Plasmática/genética , Calicreína Plasmática/urina , Estudos Prospectivos , Eliminação Renal , Insuficiência Renal Crônica/enzimologia , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/urina , Xenopus laevis
3.
Invest Ophthalmol Vis Sci ; 58(5): 2796-2803, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28564700

RESUMO

Purpose: To examine the associations between nighttime driving performance of older drivers and photopic, mesopic, and glare-based tests of visual function. Methods: Participants included 26 older drivers (71.8 ± 6.3 years), with minimal or no eye disease, but who reported vision-related nighttime driving difficulties. Nighttime driving performance was assessed on a closed-road circuit, which included intermittent glare. An overall driving performance score was calculated based on detection of signs, pedestrians, wooden animals and road markings, lane-keeping, and avoidance of low contrast hazards. Visual function tests included photopic and mesopic visual acuity (VA) and contrast sensitivity (CS). Tests of glare (Berkeley Glare and Aston Halometer) and mesopic motion sensitivity were also assessed. Regression analyses were used to explore the associations between these vision measures and nighttime driving performance. Results: The overall driving performance score was significantly reduced by intermittent glare (P = 0.002); notably, pedestrian detection decreased by 38% in the presence of intermittent glare (P < 0.001). Overall driving scores were most strongly associated with motion sensitivity (P = 0.001) and mesopic high contrast VA (P = 0.002), rather than photopic or glare-based tests. Motion sensitivity accounted for more than twice the variation in driving performance compared to photopic high contrast VA (29% vs. 14%). Conclusions: Glare reduced several aspects of nighttime driving performance. Mesopic tests of visual function, including motion sensitivity and mesopic high contrast VA, were more strongly associated with nighttime driving performance than photopic high-contrast VA. These results highlight the potential importance of nonstandard vision tests for assessing older drivers' visual capacity to drive at night.


Assuntos
Condução de Veículo , Ofuscação , Visão Mesópica/fisiologia , Desempenho Psicomotor/fisiologia , Idoso , Idoso de 80 Anos ou mais , Condução de Veículo/normas , Visão de Cores/fisiologia , Sensibilidades de Contraste/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos da Visão/fisiopatologia , Testes Visuais , Acuidade Visual/fisiologia
4.
Ophthalmic Physiol Opt ; 36(4): 465-76, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27350185

RESUMO

PURPOSE: Night-time driving difficulties are a common concern of older drivers and those with eye disease. This study aimed to develop and validate a questionnaire for assessing vision-related night driving difficulties in older drivers. METHODS: Items from existing vision-related quality of life questionnaires and driving studies were used to develop a questionnaire that was completed by 283 participants who reported visual difficulties for night driving (65% female, 50 to >80 years). The questionnaire included items relating to demographic and night driving characteristics (seven items), general vision ratings (eight items), vision-related night driving difficulties (11 items), and a single open question about specific night driving difficulties. The vision-related night driving difficulty items were analysed separately using Rasch analysis to form the vision and night driving questionnaire (VND-Q). Rasch analysis assessed validity and psychometric properties of the scale. Generalised linear regression models examined associations between VND-Q scores and age, gender, amount of night driving, self-rated vision, and eye conditions. Test-retest repeatability was assessed using intra-class correlation analysis and Bland-Altman methods of agreement for a subset of 30 participants. RESULTS: Rasch analysis indicated that a nine-item VND-Q scale was unidimensional, valid and reliable, and showed excellent discriminant ability (person separation index 3.04; person reliability 0.90). Targeting was better for those with greater self-reported night driving difficulties. Participants with self-reported bilateral eye conditions and worse self-reported general vision ratings had significantly more night driving difficulties with the VND-Q scale than individuals without eye conditions (p = 0.03) and with better general vision ratings (p < 0.001). Females reported more difficulties than males (p < 0.001) and drove shorter distances at night per week which was also associated with greater difficulties (p < 0.001). A repeatability coefficient (Rc ) of 2.07 demonstrated excellent test-retest repeatability. CONCLUSIONS: The nine-item VND-Q is a unidimensional and reliable questionnaire allowing quantification of the level of visual difficulties that older drivers report at night. The development of this questionnaire is an important step in providing a reliable and validated instrument for use to guide appropriate investigations, referrals, or interventions in clinical and research settings.


Assuntos
Condução de Veículo/psicologia , Visão Noturna/fisiologia , Psicometria/métodos , Qualidade de Vida , Inquéritos e Questionários , Acuidade Visual , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
5.
PLoS One ; 10(6): e0127162, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26039066

RESUMO

Three large lamniform shark vertebrae are described from the Lower Cretaceous of Texas. We interpret these fossils as belonging to a single individual with a calculated total body length of 6.3 m. This large individual compares favorably to another shark specimen from the roughly contemporaneous Kiowa Shale of Kansas. Neither specimen was recovered with associated teeth, making confident identification of the species impossible. However, both formations share a similar shark fauna, with Leptostyrax macrorhiza being the largest of the common lamniform sharks. Regardless of its actual identification, this new specimen provides further evidence that large-bodied lamniform sharks had evolved prior to the Late Cretaceous.


Assuntos
Tamanho Corporal , Fósseis , Tubarões/anatomia & histologia , Tubarões/classificação , Animais , Texas
6.
Ophthalmic Physiol Opt ; 34(4): 470-8, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24889086

RESUMO

PURPOSE: Older adults have increased visual impairment, including refractive blur from presbyopic multifocal spectacle corrections, and are less able to extract visual information from the environment to plan and execute appropriate stepping actions; these factors may collectively contribute to their higher risk of falls. The aim of this study was to examine the effect of refractive blur and target visibility on the stepping accuracy and visuomotor stepping strategies of older adults during a precision stepping task. METHODS: Ten healthy, visually normal older adults (mean age 69.4 ± 5.2 years) walked up and down a 20 m indoor corridor stepping onto selected high and low contrast targets while viewing under three visual conditions: best-corrected vision, +2.00 DS and +3.00 DS blur; the order of blur conditions was randomised between participants. Stepping accuracy and gaze behaviours were recorded using an eyetracker and a secondary hand-held camera. RESULTS: Older adults made significantly more stepping errors with increasing levels of blur, particularly exhibiting under-stepping (stepping more posteriorly) onto the targets (p < 0.05), while visuomotor stepping strategies did not significantly alter. Stepping errors were also significantly greater for the low compared to the high contrast targets and differences in visuomotor stepping strategies were found, including increased duration of gaze and increased interval between gaze onset and initiation of the leg swing when stepping onto the low contrast targets. CONCLUSIONS: These findings highlight that stepping accuracy is reduced for low visibility targets, and for high levels of refractive blur at levels typically present in multifocal spectacle corrections, despite significant changes in some of the visuomotor stepping strategies. These findings highlight the importance of maximising the contrast of objects in the environment, and may help explain why older adults wearing multifocal spectacle corrections exhibit an increased risk of falling.


Assuntos
Atenção/fisiologia , Destreza Motora/fisiologia , Caminhada/fisiologia , Fatores Etários , Idoso , Sensibilidades de Contraste/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acuidade Visual/fisiologia
7.
Optom Vis Sci ; 91(6): e140-4, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24811845

RESUMO

PURPOSE: This report presents a case of apparent congenital inferior rectus palsy notable for sensory adaptations that appeared to vary with direction of gaze. It is shown that readily available clinical tests and an understanding of the physiology of ocular motility can be used to help distinguish from differential diagnoses such as contralateral inferior oblique palsy or the more commonly seen Brown syndrome. CASE REPORT: A 20-year-old male optometry student reported strabismus that had been noted at birth and was diagnosed as Brown syndrome in childhood. The Parks three-step test showed primary gaze hypertropia that increased in left gaze but the "third step" (Bielschowsky head tilt test) was not successful in establishing the apparently correct diagnosis, which was later confirmed by a Hess screen. A proposed "fourth" step by Bajandas proved to be more accurate in this case of inferior rectus palsy. Sensory tests revealed adaptation patterns that varied with gaze direction and showed a cyclotorsional element. The patient reported being relatively unconcerned about his condition as he seemed to be able to voluntarily use a form of shallow suppression to reduce awareness of diplopic images. CONCLUSIONS: Although it is common to consider suppression and retinal correspondence status as hardwired and relatively constant for an individual patient, this case demonstrates that these sensory adaptations are likely to be far more complex and transitory. An understanding of both motor and sensory repercussions of ocular motility dysfunction assists differentiation between benign and sinister causes of nonconcomitant strabismus.


Assuntos
Adaptação Ocular/fisiologia , Transtornos da Motilidade Ocular/diagnóstico , Músculos Oculomotores/inervação , Doenças do Nervo Oculomotor/diagnóstico , Diagnóstico Diferencial , Técnicas de Diagnóstico Oftalmológico , Humanos , Masculino , Transtornos da Motilidade Ocular/fisiopatologia , Doenças do Nervo Oculomotor/fisiopatologia , Adulto Jovem
8.
Biofouling ; 30(1): 51-68, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24199998

RESUMO

Copper-based epoxy and ablative antifouling painted panels were exposed in natural seawater to evaluate environmental loading parameters. In situ loading factors including initial exposure, passive leaching, and surface refreshment were measured utilizing two protocols developed by the US Navy: the dome method and the in-water hull cleaning sampling method. Cleaning techniques investigated included a soft-pile carpet and a medium duty 3M(™) pad for fouling removal. Results show that the passive leach rates of copper peaked three days after both initial deployment and cleaning events (CEs), followed by a rapid decrease over about 15 days and a slow approach to asymptotic levels on approximately day 30. Additionally, copper was more bioavailable during a CE in comparison to the passive leaching that immediately followed. A paint life cycle model quantifying annual copper loading estimates for each paint and cleaning method based on a three-year cycle of painting, episodic cleaning, and passive leaching is presented.


Assuntos
Incrustação Biológica/prevenção & controle , Cobre/química , Pintura/toxicidade , Navios , Disponibilidade Biológica , Cobre/toxicidade , Propriedades de Superfície , Qualidade da Água
9.
Kidney Int ; 70(12): 2124-30, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17063178

RESUMO

Chronic microinflammation increases cardiovascular morbidity in chronic hemodialysis (HD) patients. Previously published studies are controversial with respect to acute effects of HD treatment on up- or downregulation of cytokine protein levels. Twenty-nine chronic HD patients were hemodialysed for 4 h with a 4008 dialyser using high-flux membranes. Patients were separated into a low (up to 1 mg/dl) and a high (1.1 to 5.5 mg/dl) C-reactive protein (CRP) group. Blood was drawn before HD and 240 min after initiation of HD. Acute changes of transcript levels encoding pro- and anti-inflammatory mediators were analyzed in RNA stabilized immediately from blood leukocytes using microarray analysis (n=1) and quantitative real-time polymerase chain reaction (PCR) (Light Cycler) (n=29). In both patient groups, HD treatment significantly increased the transcript levels of several pro-inflammatory cytokines, such as tumor necrosis factor alpha and interleukin-8 (IL-8), and chemokine receptors such as C-X-C chemokine receptor type 4, C-C chemokine receptor type 7, and the fractakine receptor CX3C chemokine receptor 1. In the low CRP group, the increase of transcript levels for anti-inflammatory IL-1-receptor antagonist and of the receptor for the anti-inflammatory cytokines IL-10 and interferon gamma was significantly more pronounced than in the high CRP group. Subgroup analysis revealed no difference between diabetic vs non-diabetic patients. These observations point towards a marked influence of a routine hemodialysis treatment on transcription in leukocytes of pro- and anti-inflammatory cytokines and receptors relevant for microinflammation. Diminished upregulation of receptors for anti-inflammatory factors in HD patients with high CRP levels could contribute to enhanced microinflammation in those patients.


Assuntos
Proteína C-Reativa/metabolismo , Citocinas/genética , Inflamação/prevenção & controle , Falência Renal Crônica/imunologia , Falência Renal Crônica/terapia , Diálise Renal/métodos , Idoso , Proteína C-Reativa/imunologia , Feminino , Humanos , Inflamação/imunologia , Leucócitos/fisiologia , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Receptores de Quimiocinas/genética , Receptores de Complemento/genética , Receptores de Citocinas/genética , Diálise Renal/instrumentação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Gênica/imunologia
10.
Oncology ; 51(4): 320-2, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8208513

RESUMO

Mutated ras genes are found in a variety of human tumors. For biological activity the gene product p21 ras needs to be bound to the cell membrane by a farnesyl residue. Treatment of tumor cells with lovastatin reduces the availability of farnesyl pyrophosphate for the modification of the ras proteins. The membrane localization of p21 ras has been reduced by 30-36% after the tumor cells have grown in the presence of 10 microM lovastatin for 7 days. The extent of the inhibition depends on the growth kinetics of the cell lines.


Assuntos
Genes ras/genética , Leucemia Mieloide/metabolismo , Lovastatina/farmacologia , Neuroblastoma/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Doença Aguda , Humanos , Leucemia Mieloide/genética , Mutação , Proteínas Proto-Oncogênicas p21(ras)/efeitos dos fármacos , Células Tumorais Cultivadas
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