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Background: The use of 3D imaging is becoming increasingly common, so too is the use of fiducial markers to identify/track regions of interest and assess material deformation. While many different materials have been used as fiducials, they are often used in isolation, with little comparison to one another. Objective: In the current study, we aim to directly compare different Computed Tomography (CT and µCT) fiducial materials, both metallic and nonmetallic. Methods: µCT imaging was performed on a soft-tissue structure, in this case heart valve tissue, with various markers attached. Additionally, we evaluated the same markers with DiceCT stained tissue in a fluid medium. Eight marker materials were tested in all. Results: All of the metallic markers generated significant artifacts and were found unsuitable for soft-tissue µCT imaging, whereas alumina markers were found to perform the best, with excellent contrast and consistency. Conclusions: These findings support the further use of alumina as fiducial markers for soft material and tissue studies that utilize CT and µCT imaging.
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Implementation of wildfire- and climate-adaptation strategies in seasonally dry forests of western North America is impeded by numerous constraints and uncertainties. After more than a century of resource and land use change, some question the need for proactive management, particularly given novel social, ecological, and climatic conditions. To address this question, we first provide a framework for assessing changes in landscape conditions and fire regimes. Using this framework, we then evaluate evidence of change in contemporary conditions relative to those maintained by active fire regimes, i.e., those uninterrupted by a century or more of human-induced fire exclusion. The cumulative results of more than a century of research document a persistent and substantial fire deficit and widespread alterations to ecological structures and functions. These changes are not necessarily apparent at all spatial scales or in all dimensions of fire regimes and forest and nonforest conditions. Nonetheless, loss of the once abundant influence of low- and moderate-severity fires suggests that even the least fire-prone ecosystems may be affected by alteration of the surrounding landscape and, consequently, ecosystem functions. Vegetation spatial patterns in fire-excluded forested landscapes no longer reflect the heterogeneity maintained by interacting fires of active fire regimes. Live and dead vegetation (surface and canopy fuels) is generally more abundant and continuous than before European colonization. As a result, current conditions are more vulnerable to the direct and indirect effects of seasonal and episodic increases in drought and fire, especially under a rapidly warming climate. Long-term fire exclusion and contemporaneous social-ecological influences continue to extensively modify seasonally dry forested landscapes. Management that realigns or adapts fire-excluded conditions to seasonal and episodic increases in drought and fire can moderate ecosystem transitions as forests and human communities adapt to changing climatic and disturbance regimes. As adaptation strategies are developed, evaluated, and implemented, objective scientific evaluation of ongoing research and monitoring can aid differentiation of warranted and unwarranted uncertainties.
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Incêndios , Incêndios Florestais , Ecossistema , Florestas , Humanos , América do NorteRESUMO
BACKGROUND: Heart valve computational models require high quality geometric input data, commonly obtained using micro-computed tomography. Whether in the open or closed configuration, most studies utilize dry valves, which poses significant challenges including gravitational and surface tension effects along with desiccation induced mechanical changes. OBJECTIVE: These challenges are overcome by scanning in a stress-free configuration in fluid. Utilizing fluid backgrounds however reduces overall contrast due to the similar density of fluid and tissue. METHODS: The work presented here demonstrates imaging of the mitral valve by utilizing an iodine-based staining solution to improve the contrast of valve tissue against a fluid background and investigates the role of stain time and concentration. RESULTS: It is determined that an Olea europaea oil bath with a relatively high concentration, short stain time approach produces high quality imagery suitable for creating accurate 3D renderings. CONCLUSIONS: Micro-CT scanning of heart valves in fluid is shown to be feasible using iodine staining techniques.
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OBJECTIVES: To estimate the total costs of treating head and neck cancers, specifically oropharyngeal, laryngeal and oral cavity cancer, in secondary care facilities in England during the period 2006/2007 to 2010/2011. DESIGN: Patient records were extracted from an English hospital database to estimate the number of patients treated for oropharyngeal, laryngeal and oral cavity cancer in England. Identified resource use was linked to published United Kingdom cost estimates to quantify the reimbursement of treatment through the Payment by Results system. SETTING: Retrospective hospital data analysis. PARTICIPANTS: From the hospital data, patient records of patients treated for oropharyngeal, laryngeal and oral cavity cancer were selected. MAIN OUTCOME MEASURES: Annual total costs of treatment, stratified by inpatient and outpatient setting and by male and female patients. RESULTS: From 2006/2007 to 2010/2011, total costs of treatment across the three head and neck cancer sites were estimated to be approximately £309 million, with 90% attributable to inpatient care (bundled costs). Oropharyngeal cancer accounted for 37% of total costs. Costs and patient numbers increased over time, largely due to a rise in oropharyngeal cancer, where total costs increased from £17.21 million to £30.32 million, with over 1400 (52%) more inpatients treated in 2010/11 compared to 2006/07. CONCLUSIONS: In 4 years, the number of patients with oropharyngeal cancer receiving some form of inpatient care increased by more than half, and associated costs increased by three quarters. This reinforces the case for prevention and early detection strategies to help contain this epidemiological and economic burden.
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Efeitos Psicossociais da Doença , Gastos em Saúde/tendências , Neoplasias Orofaríngeas/economia , Terapia Combinada/economia , Bases de Dados Factuais , Inglaterra , Humanos , Neoplasias Orofaríngeas/terapia , Estudos RetrospectivosRESUMO
INTRODUCTION: Haemophilia is a bleeding disorder characterized by musculoskeletal bleeding. Trauma-induced bleeding into joints and muscles may be associated with participation in physical activities. Recognizing this, persons with haemophilia may limit physical activities to avoid bleeding. The characterization of physical activity profiles (type, intensity, frequency and duration) in children with differing severities of haemophilia has not been well documented. This is required to better understand the relationship between physical activity and bleeding in children with haemophilia. AIM: This study was a prospective, cross-sectional, observational study to compare the quantity, type and intensity of physical activity as measured by accelerometry in boys with different haemophilia severities. METHODS: Subjects wore an accelerometer daily for 1 week and completed validated self-report PedHAL and 3DPAR questionnaires. Accelerometer activity levels were classified as sedentary, light, moderate or vigorous. RESULTS: A total of 66 males were enrolled, 24 had mild/moderate and 42 had severe haemophilia. Subjects average age was 11.52 years (±3.99) and their average BMI was 20.74 kg m(2) (±5.68). Boys with severe haemophilia reported significantly more time per day spent in sedentary activities compared to those with mild/moderate haemophilia. Furthermore, the amount of time engaged in sedentary activities increased with age in those boys with severe haemophilia, whereas the opposite was true in those with mild/moderate haemophilia. CONCLUSION: We speculate that prophylaxis in children with severe haemophilia permitted them to engage in similar amounts of moderate to vigorous physical activity (MVPA) as children with mild/moderate haemophilia. Increasing sedentary time in the severe cohort with age may be attributed to increasing arthropathy among other psychosocial factors.
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Exercício Físico , Hemofilia A/epidemiologia , Atividade Motora , Acelerometria , Adolescente , Criança , Estudos Transversais , Progressão da Doença , Hemofilia A/fisiopatologia , Humanos , Masculino , Projetos Piloto , Estudos Prospectivos , Autorrelato , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To conduct enhanced surveillance for signals of teratogenesis following use of the neuraminidase inhibitors zanamivir and oseltamivir in the treatment or post-exposure prophylaxis of 2009 A/H1N1 influenza during pregnancy. DESIGN: Prospective cohort study, using national surveillance data collected by the UK Teratology Information Service (UKTIS) during the 2009 A/H1N1 pandemic. SETTING: United Kingdom. POPULATION: Pregnant women who were reported to UKTIS by healthcare professionals seeking advice about exposure to zanamivir and oseltamivir or to other non-teratogenic drugs. METHODS: Pregnancy outcomes were collected for prospectively reported pregnancies exposed to zanamivir (n = 180) or oseltamivir (n = 27), and compared with a reference group of 575 prospectively reported pregnancies exposed to non-teratogenic drugs over the same period. MAIN OUTCOME MEASURES: Rates of major congenital malformation, preterm delivery and low birth weight. RESULTS: No significant differences in overall rates of major malformation in live-born infants [adjusted odds ratios (aOR): zanamivir 0.37 (95% confidence interval 0.02-2.70); oseltamivir aOR 0.81 (0.05, 14.15)], preterm delivery [aOR: zanamivir 0.95 (0.45, 1.89); oseltamivir aOR 1.68 (0.38, 5.38)] or low birth weight [aOR: zanamivir 0.94 (0.25, 2.90); oseltamivir aOR 4.12 (0.59, 17.99)] were observed following exposure at any gestation. No major malformations were reported in 37 zanamivir or eight oseltamivir first trimester exposures. CONCLUSION: These surveillance data do not provide a signal that use of zanamivir or oseltamivir in pregnancy is associated with an increased risk of the adverse pregnancy outcomes studied but the data are too limited to state conclusively that there is no increase in risk.
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Antivirais/uso terapêutico , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/tratamento farmacológico , Influenza Humana/epidemiologia , Oseltamivir/uso terapêutico , Pandemias , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez , Zanamivir/uso terapêutico , Adolescente , Adulto , Antivirais/efeitos adversos , Monitoramento Epidemiológico , Feminino , Humanos , Pessoa de Meia-Idade , Oseltamivir/efeitos adversos , Gravidez , Estudos Prospectivos , Reino Unido , Adulto Jovem , Zanamivir/efeitos adversosRESUMO
OBJECTIVES: To investigate auditory dysfunction in patients with tinnitus and normal hearing thresholds using two sensitive audiological measures. DESIGN: The study was designed to investigate the characteristics of Audioscan and DPOAE tests in tinnitus patients with normal hearing thresholds. Audioscan and DPOAE notches were analysed and compared. All tests were performed in a sound-treated chamber or in a sound-treated room. STUDY SAMPLE: Forty-five tinnitus patients with normal hearing thresholds were examined following a written clinical protocol. RESULTS: The averaged hearing levels obtained from tinnitus participants were significantly worse at high frequencies than those derived from the normative data. There was a significantly higher prevalence of Audioscan and DPOAE notches, whose central frequencies matched tinnitus frequencies in the mid-frequency regions, but not in the low- and high-frequency regions. A significant correlation was found between the centre frequencies of the Audioscan notches and the DPOAE notches from 500 to 4000 Hz. CONCLUSION: Tinnitus in different frequency regions may be associated with different underlying mechanisms of tinnitus generation. Some negative results on the Audioscan and DPOAE notches matching tinnitus pitches may be due to a limited set of discrete frequencies used for the tinnitus pitch matching test.
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Audiometria de Tons Puros/métodos , Limiar Auditivo/fisiologia , Otoscopia/métodos , Discriminação da Altura Tonal/fisiologia , Zumbido/diagnóstico , Zumbido/fisiopatologia , Adulto , Audiometria de Tons Puros/normas , Doenças Cocleares/complicações , Doenças Cocleares/diagnóstico , Doenças Cocleares/fisiopatologia , Feminino , Audição/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Emissões Otoacústicas Espontâneas/fisiologia , Otoscopia/normas , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Zumbido/etiologia , Adulto JovemRESUMO
OBJECTIVE: This contribution addresses the risk associated with exposure to statins during pregnancy. DESIGN: Multicentre observational prospective controlled study. SETTING: European Network of Teratology Information Services. POPULATION: Pregnant women who contacted one of 11 participating centres, seeking advice about exposure to statins during pregnancy, or to agents known to be nonteratogenic. METHODS: Pregnancies exposed during first trimester to statins were followed up prospectively, and their outcomes were compared with a matched control group. MAIN OUTCOME MEASURES: Rates of major birth defects, live births, miscarriages, elective terminations, preterm deliveries and gestational age and birthweight at delivery. RESULTS: We collected observations from 249 exposed pregnancies and 249 controls. The difference in the rate of major birth defects between the statin-exposed and the control groups was small and statistically nonsignificant (4.1% versus 2.7% odds ratio [OR] 1.5; 95% confidence interval [95% CI] 0.5-4.5, P = 0.43). In an adjusted Cox model, the difference between miscarriage rates was also small and not significant (hazard ratio 1.36, 95% CI 0.63-2.93, P = 0.43). Premature birth was more frequent in exposed pregnancies (16.1% versus 8.5%; OR 2.1, 95% CI 1.1-3.8, P = 0.019). Nonetheless, median gestational age at birth (39 weeks, interquartile range [IQR] 37-40 versus 39 weeks, IQR 38-40, P = 0.27) and birth weight (3280 g, IQR 2835-3590 versus 3250 g, IQR 2880-3630, P = 0.95) did not differ between exposed and non-exposed pregnancies. CONCLUSIONS: This study did not detect a teratogenic effect of statins. Its statistical power remains insufficient to challenge current recommendations of treatment discontinuation during pregnancy.
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Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Exposição Materna/efeitos adversos , Resultado da Gravidez/epidemiologia , Teratogênicos , Anormalidades Induzidas por Medicamentos/epidemiologia , Aborto Induzido/estatística & dados numéricos , Aborto Espontâneo/epidemiologia , Adulto , Coeficiente de Natalidade , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Idade Materna , Gravidez , Primeiro Trimestre da Gravidez , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Sleep, physical activity (PA) and sedentary behavior (SED) have bidirectional associations with mental health in children. The relationships among sleep, PA, SED, with depressive and fatigue symptoms have not been investigated in Pediatric Onset Multiple Sclerosis (POMS) but are needed to inform sleep and PA behavior change interventions. OBJECTIVES: (1) To describe sleep quality including: sleep efficiency, latency, total sleep time, number of awakenings, time in bed, and wake after sleep onset using actigraphy in children and adolescents ages 11 to 18 diagnosed with POMS, and to compare these sleep metrics to those of an age- and sex-matched non-MS group (2) To examine the relationship between time spent in sedentary, light (LIPA), moderate and vigorous PA (MVPA), sleep quality, with depression, fatigue, and quality of life in children and adolescents with POMS and an age and sex matched non-MS group. METHODS: A cross-sectional study recruited children and adolescents with POMS ages 11 to 18 years followed at a tertiary pediatric hospital (Toronto, Canada) and an age and sex matched non-MS group from the general population. Participants were consented prior to initiation of study procedures. Participants wore an Actiwatch monitor and GT3X accelerometer and completed standardized questionnaires validated to capture data on sleep disturbances, depression, fatigue, and quality of life. Objective sleep data were collected using an Actiwatch including sleep efficiency, total sleep time, number of awakenings, wake after sleep onset (WASO), and sleep latency. A GT3X accelerometer was used to collect PA data including time spent in SED, light (LPA), and moderate to vigorous (MVPA) PA. Correlational analyses and tests of difference were used to compare the groups. RESULTS: 25 POMS (21F; 16.6 years ±1.1 yrs., median Expanded Disability Status Scale (EDSS) =1.5, IQR=1) and 25 Non-MS (22 F; 16±1.3 yrs.) took part. POMS had higher BMI (T= -5.1, P<0.001) compared to Non-MS. No differences in sleep efficiency (MS mean = 87%, vs. 88%) sleep time (MS Mean = 7.3 hrs. vs. 7.4 hrs.,), WASO (MS mean=37 mins. vs. 36 mins), latency (MS mean=15 mins vs. 11 mins), SED (MS mean =763 mins. vs. 730 mins) or PA (MS, mean LPA = 68 mins. vs 60 mins; MS mean MVPA = 12.7 mins. vs. 12.4 mins). Within POMS, higher sleep efficiency was associated with more SED (SR= 0.4, p = 0.05), while higher sleep efficiency was associated with less SED in Non-MS (SR = -0.7, p< 0.0). In children with POMS, less sleep time, shorter sleep onset latency and more WASO was associated with more SED (SR range = -0.45 to -0.58, P< 0.01). Higher sleep efficiency was associated with less fatigue. Less WASO was associated with lower depression, lower fatigue (SR = 0.67, p<0.01) and better quality of life (SR= -0.6, p<0.01). Greater LPA was associated with lower sleep onset latency (-0.45, p<0.05). CONCLUSIONS: Children with POMS did not differ in Actiwatch monitored sleep quality metrics. However, within the POMS group sleep quality was associated with better fatigue, depression and QOL. Further, total sleep time, WASO and latency associated with time spent SED and LPA, which independently associate with mental health outcome. Longitudinal work should determine the temporal associations between WASO, sleep latency, sleep time, PA, and mental health outcomes and whether reallocation of specific sleep or PA behaviors (time to sleep, total sleep time, sedentary to MVPA) result in improved depression fatigue, or quality of life in children and adolescents with POMS.
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Esclerose Múltipla , Qualidade de Vida , Humanos , Criança , Adolescente , Estudos Transversais , Esclerose Múltipla/epidemiologia , Exercício Físico , Sono , Fadiga/epidemiologia , Fadiga/etiologia , Acelerometria/métodosRESUMO
OBJECTIVE: To evaluate if pelvic or hip width predisposed women to developing greater trochanteric pain syndrome (GTPS). DESIGN: Prospective case control study. PARTICIPANTS: Four groups were included in the study: those gluteal tendon reconstructions (n=31, GTR), those with conservatively managed GTPS (n=29), those with hip osteoarthritis (n=20, OA) and 22 asymptomatic participants (ASC). METHODS: Anterior-posterior pelvic x-rays were evaluated for femoral neck shaft angle; acetabular index, and width at the lateral acetabulum, and the superior and lateral aspects of the greater trochanter. Body mass index, and waist, hip and greater trochanter girth were measured. Data were analysed using a one-way analysis of variance (ANOVA; posthoc Scheffe analysis), then multivariate analysis. RESULTS: The GTR group had a lower femoral neck shaft angle than the other groups (p=0.007). The OR (95% CI) of having a neck shaft angle of less than 134°, relative to the ASC group: GTR=3.33 (1.26 to 8.85); GTPS=1.4 (0.52 to 3.75); OA=0.85 (0.28 to 2.61). The OR of GTR relative to GTPS was 2.4 (1.01 to 5.6). No group difference was found for acetabular or greater trochanter width. Greater trochanter girth produced the only anthropometric group difference (mean (95% CI) in cm) GTR=103.8 (100.3 to 107.3), GTPS=105.9 (100.2 to 111.6), OA=100.3 (97.7 to 103.9), ASC=99.1 (94.7 to 103.5), (ANOVA: p=0.036). Multivariate analysis confirmed adiposity is associated with GTPS. CONCLUSION: A lower neck shaft angle is a risk factor for, and adiposity is associated with, GTPS in women.
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Adiposidade/fisiologia , Artralgia/etiologia , Colo do Fêmur/patologia , Osteoartrite do Quadril/patologia , Tendinopatia/patologia , Adulto , Idoso , Análise de Variância , Antropometria , Artralgia/patologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Ossos Pélvicos/patologia , Exame Físico , Estudos Prospectivos , Fatores de Risco , Síndrome , Adulto JovemRESUMO
BACKGROUND: Higher levels of moderate to vigorous physical activity (MVPA) associate with disease activity in pediatric multiple sclerosis (MS). Further, measures of retinal integrity associate with lower brain atrophy, yet the relationship of retinal integrity with MVPA has not been investigated. OBJECTIVE: To determine the relationship between MVPA and retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness in patients with MS, myelin oligodendrocyte glycoprotein-associated disorders (MOGAD), neuromyelitis optica spectrum disorder (NMOSD), and monophasic acquired demyelinating syndromes (monoADS). METHODS: 150 consecutive children ≤18 y.o with neuroinflammatory disorders were included. Outcomes included the Godin Leisure Time Activity Questionnaire (GLTEQ) modeled as both a continuous and categorical variable (any vs no MVPA/Strenuous activity), and RNFL and GCIPL using linear mixed models (JASP 0.14.1). RESULTS: An association was identified between MVPA with RNFL thickness (F (1,133) = 8.40, p = .004) and GCIPL thickness (F(1, 131) = 7.68, p = .006). In the MS cohort, any strenuous physical activity was associated with greater RNFL (F(1,35) = 7.30, p = .011) and GCIPL thickness (F(1,35) = 8.73, p =.006). CONCLUSIONS: Any MVPA participation is associated with higher RNFL and GCIPL thickness across neuroinflammatory disorders.
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Esclerose Múltipla , Células Ganglionares da Retina , Adolescente , Benchmarking , Criança , Exercício Físico , Humanos , Doenças Neuroinflamatórias , Tomografia de Coerência ÓpticaRESUMO
BACKGROUND: Youth with multiple sclerosis (MS) have high levels of disease activity, depression and fatigue, and lower moderate to vigorous physical activity (PA). PA participation is associated with lower disease activity, depression and fatigue as well as higher self-efficacy, goal setting and decreased barriers. These latter constructs may be targeted by an intervention program for behavior change, and such intervention must account for disease rarity, geographical proximity and time constraints which limit the feasibility, accessibility, and sustainability of implementing a PA intervention in youth with MS. We have developed a theory-informed mobile-app based PA promotion program to address these barriers, Active Teens with Multiple Sclerosis (ATOMIC) and herein report the feasibility of delivering this intervention in youth with MS. OBJECTIVE: To determine the feasibility of delivering the ATOMIC program to youth with MS. METHODS: Fifteen youth with MS (13F, 16.6⯱â¯1.2 years) followed at the Hospital for Sick Children were enrolled in the ATOMIC intervention. Participants underwent a standard clinical evaluation; an exercise test to determine cardiorespiratory fitness; 7-day PA monitoring with an accelerometer; and completed standardized depression, fatigue questionnaires at baseline and post-intervention. Social cognitive scales related to self-efficacy, self-management, goal setting, perceived barriers, outcome expectancy, and social support were completed at baseline, six and 12-weeks. The 12-week mobile app PA intervention was informed by Social Cognitive Theory (SCT) and included: individualized PA coaching, PA self-monitoring (Fitbit), goal setting, social support and MS specific educational modules. Feasibility was defined as (1) meeting the recruitment target of 15 participants within a one-year period; (2) completion of ≥80% of study related questionnaires and testing; (3) a drop-out rate of less than 20%, and (4) adherence to the ATOMIC intervention program components of ≥80% (Fitbit wear, PA coaching calls, modules). RESULTS: From March 2018 to April 2019, 53% of youth approached agreed to participate (15/28). 13/15 participants completed the intervention. 36 of the possible 39 coaching calls (92%: 3 possible phone calls per participant); 89% wear adherence to FitbitCharge2 data (meanâ¯=â¯75⯱â¯16.6 days of 84 days); and 5/12 (42%) of modules were completed. An average 8.4% (SD= 40%, rangeâ¯=â¯-74.0 to 176%) increase in Fitbit steps above the first week of the intervention were observed. PA level from accelerometry at 12-weeks, aerobic fitness, depression and fatigue were unchanged. SCT scales indicated an increase in social support from friends (0.67-points, Tâ¯=â¯2.7, pholm=0.04), and a decrease in outcome expectancy (-2.7, Tâ¯=â¯3.0, pholm=0.03). There were no differences in self-efficacy, self-management or perceived barriers post intervention. CONCLUSIONS: Our results indicate that the ATOMIC program is feasible for delivery in youth with MS. Future work is needed to understand how to best implement each element of SCT through added features in the mobile-app, and to evaluate how the individual components of SCT mediate change in PA behaviours of youth with MS.
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Aplicativos Móveis , Esclerose Múltipla , Adolescente , Criança , Exercício Físico , Fadiga/complicações , Estudos de Viabilidade , Humanos , Esclerose Múltipla/complicaçõesRESUMO
BACKGROUND: Adiponectin (Adipoq), a protein secreted by adipocytes in inverse proportion to the adipose mass present, modulates energy homeostasis and increases insulin sensitivity. Tissue Adipoq signaling decreases in settings of maternal diabetes, polycystic ovary syndrome (PCOS) and endometriosis, conditions which are associated with reproductive difficulty. Our objective was to define the expression and hormonal regulation of Adipoq and its receptors in the mouse preimplantation embryo and uterus. METHODS AND RESULTS: By real-time quantitative PCR, mRNA transcripts for Adipoq, AdipoR1, AdipoR2, Ppara, Ppard, FATP1 (SLC27A1) and acyl CoA oxidase (Acox1) were identified in mouse 2-cell and 8-cell embryos, while blastocyst stage embryos and trophoblast stem (TS) cells expressed mRNA for all genes except Adipoq. Protein expression of Adipoq, AdipoR1, AdipoR2, the insulin sensitive transporters GLUT8 (Slc2A8), GLUT12 (Slc2A12) and p-PRKAA1 was identified by immunofluorescence staining in all stages of preimplantation embryos including the blastocyst. In situ hybridization demonstrated the presence of Adipoq, AdipoR1 and AdipoR2 mRNA in the mouse decidual cells of the implantation site and in artificially decidualized cells, and the expression of these proteins was confirmed by western blotting. Flow cytometry confirmed cell surface expression of AdipoR1 and AdipoR2 in TS cells and decidual cells. CONCLUSIONS: These results suggest for the first time that Adipoq signaling may play an important role in preimplantation embryo development and uterine receptivity by autocrine and paracrine methods in the mouse. Implantation failures and pregnancy loss, specifically those experienced in women with maternal metabolic conditions such as diabetes, obesity and PCOS, may be the result of aberrant Adipoq and AdipoR1 and AdipoR2 expression and suboptimal decidualization in the uterus.
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Adiponectina/metabolismo , Blastocisto/metabolismo , Decídua/metabolismo , Receptores de Adiponectina/metabolismo , Adiponectina/genética , Adiponectina/fisiologia , Animais , Western Blotting , Implantação do Embrião , Desenvolvimento Embrionário , Feminino , Citometria de Fluxo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Hibridização In Situ , Camundongos , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Receptores de Adiponectina/genética , Receptores de Adiponectina/fisiologia , Transdução de SinaisRESUMO
Immune complexes containing human gamma (g)1 or murine g2a antibodies generate secondary effector mechanisms via Fc receptor binding or complement activation, whereas those containing human g4 or murine g1 antibodies generally do not. Therefore, isotype selection of therapeutic antibodies may have important clinical consequences. In a rabbit model of human tumor necrosis factor (rhuTNF)-induced pyrexia, a murine/human chimeric g4 anti-human TNF-alpha monoclonal antibody (mAb) (cCB0011) showed a dose-dependent inhibition of pyrexia, whereas a g1 isotype variant of the same mAb gave a marked pyrexia that was seen at all doses indicative of an immune complex-mediated response. To investigate whether isotype difference could influence mAb efficacy in pathological disease states, hamster/murine chimeric g1 and g2a anti-murine TNF-alpha mAbs (TN3g1, TN3g2a) were studied in experimental shock in mice and rats. In lipopolysaccharide-induced shock in mice, treatment with TN3g1 mAb at 30 and 3 mg/kg resulted in 90% survival by 72 h (p < or = 0.004), and prolonged survival to 45 h (p < or = 0.05), respectively, compared with 100% mortality by 27 h in controls. In contrast, a g2a isotype variant of the same mAb (30 mg/kg) resulted in only 10% survival by 72 h (p < or = 0.05). In a neutropenic sepsis model in rats there was greater survival in animals receiving the g1 isotype of TN3 compared with g2a isotype variant (70 vs. 27%; p < or = 0.005) with 100% mortality in the controls. These differences were not due to the pharmacokinetic profiles of the mAbs. In models of experimental shock antibody isotype can affect outcome with inactive isotypes (human g4 and murine g1) being more efficacious than active isotypes (human g1 and murine g2a).
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Anticorpos Monoclonais/uso terapêutico , Febre/terapia , Isotipos de Imunoglobulinas/toxicidade , Choque Séptico/terapia , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/toxicidade , Animais , Anticorpos Monoclonais/metabolismo , Febre/induzido quimicamente , Humanos , Isotipos de Imunoglobulinas/uso terapêutico , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Coelhos , Proteínas Recombinantes de Fusão/farmacocinética , Proteínas Recombinantes de Fusão/uso terapêutico , Proteínas Recombinantes/toxicidade , Choque Séptico/induzido quimicamente , Choque Séptico/imunologiaRESUMO
It has been previously suggested that oxytocin (Oxt) may act as a natural antipsychotic. To test this hypothesis, we investigated whether disruption of the oxytocin gene (Oxt-/-) made mice more susceptible to the psychosis-related effects of amphetamine (Amp), apomorphine (Apo) and phencyclidine (PCP). We examined drug-induced changes in the prepulse inhibition (PPI) of the startle reflex, a measure of sensorimotor gating deficits characteristic of several psychiatric and neurological disorders, including schizophrenia. We found that treatment with Amp, Apo and PCP all had effects on PPI. However, in Oxt-/- mice, but not Oxt+/+ mice, PCP treatment resulted in large PPI deficits. As PCP is a noncompetitive N-methyl-D-aspartic acid receptor antagonist, these findings suggest that the absence of Oxt alters the glutamatergic component of the PPI.
Assuntos
Inibição Neural/genética , Ocitocina/deficiência , Reflexo de Sobressalto/genética , Filtro Sensorial/genética , Estimulação Acústica/métodos , Anfetamina/farmacologia , Análise de Variância , Animais , Apomorfina/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Inibição Neural/efeitos dos fármacos , Fenciclidina/farmacologia , Psicoacústica , Reflexo de Sobressalto/efeitos dos fármacos , Filtro Sensorial/efeitos dos fármacos , Fatores SexuaisRESUMO
OBJECTIVES: To investigate the relationship between those issues concerning quality of life in patients with neurofibromatosis type 2 (NF2) as identified by the closed set NF2 questionnaire and the eight norm-based measures and the physical component summary (PCS) and mental component summary (MCS) scores of the Short Form-36 (SF-36) Questionnaire. DESIGN: Postal questionnaire study. SETTING: Questionnaires sent to subjects' home addresses. PARTICIPANTS: Eighty-seven adult subjects under the care of the Manchester Multidisciplinary NF2 Clinic were invited to participate. MAIN OUTCOME MEASURES: Sixty-two (71%) completed sets of closed set NF2 questionnaires and SF-36 questionnaires were returned. RESULTS: Subjects with NF2 scored less than the norm of 50 on both the physical component summary and mental component summary scores and the eight individual norm-based measures of the Short Form-36 questionnaire. Correlations (using Kendall's tau) were examined between patients' perceptions of their severity of difficulty with the following activities and the eight norm-based measures and the physical component summary and mental component summary scores of the Short Form-36 questionnaire: Communicating with spouse/significant other (N = 61). The correlation coefficients were significant at the 0.01 level for the mental component summary score, together with three of the norm-based scores [vitality (VT), social functioning and role emotional]. Social communication (N = 62). All 10 correlations were significant at the 0.01 or 0.001 level. Balance (N = 59). All 10 correlations were highly significant at the P < 0.001 level. Hearing difficulties (N = 61). All correlations were significant at either the 0.01 level or less apart from the mental component summary score and three of the norm-based scores (role physical, VT and mental health). Mood change (N = 61). All correlations were significant at the 0.01 level or less, apart from one norm-based score (role physical). CONCLUSIONS: The Short Form-36 questionnaire has allowed us to relate patients' perceptions of their difficulties, as identified by the closed set NF2 questionnaire, to the physical and mental domains measured by this validated and widely used scale, and has provided further insight into areas of functioning affected by NF2.
Assuntos
Saúde Mental , Neurofibromatose 2/psicologia , Percepção/fisiologia , Qualidade de Vida/psicologia , Inquéritos e Questionários/normas , Adulto , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
Cotton remains from four archeological sites in central coastal Peru, representing a time sequence from about 2500 to 1000 B.C., were compared with similar materials obtained from living wild and cultivated forms of Gossypium barbadense L. The comparison revealed that the archeological cotton samples were primitive forms of Gossypium barbadense, differing little from present-day wild forms of the same species. Although not the earliest cottons recorded for the New World, they appear to represent the earliest stages of cotton domestication yet recorded.
RESUMO
Near-infrared images of Venus, obtained from a global network of ground-based observatories during January and February 1990, document the morphology and motions of the night-side near-infrared markings before, during, and after the Galileo Venus encounter. A dark cloud extended halfway around the planet at low latitudes (>+/-40 degrees ) and persisted throughout the observing program. It had a rotation period of 5.5 +/- 0.15 days. The remainder of this latitude band was characterized by small-scale (400 to 1000 kilometers) dark and bright markings with rotation periods of 7.4 +/- 1 days. The different rotation periods for the large dark cloud and the smaller markings suggests that they are produced at different altitudes. Mid-latitudes (+/-40 degrees to 60 degrees ) were usually occupied by bright east-west bands. The highest observable latitudes (+/-60 degrees to 70 degrees ) were always dark and featureless, indicating greater cloud opacity. Maps of the water vapor distribution show no evidence for large horizontal gradients in the lower atmosphere of Venus.
RESUMO
Prescribed fire was investigated as a method for controlling ixodid and argasid ticks in chaparral habitats in northern California. Two experimental and two adjacent control plots within a wildlife preserve were monitored for 1 yr postburn. Ticks were collected by flagging vegetation, by CO2-baited pitfall trap, and by live-trapping rodents. Twice as many rodents were caught at control sites compared with burn sites and no dusky-footed woodrats, Neotoma fuscipes Baird, were found in the treatment sites postburn. This species is known to be a reservoir of the agents of Lyme disease, Borrelia burgdorferi sensu stricto Johnson, Schmid, Hyde, Steigerwalt & Brenner, and human granulocytic anaplasmosis, Anaplasma phagocytophilum Dumler, Barbet, Bekker, Dasch, Palmer, Ray, Rikihisa, Rurangirwa. Six ixodid tick species were removed from rodents (Ixodes pacificus Cooley & Kohls, Ixodes jellisoni Cooley & Kohls, Ixodes spinipalpis Hadwen & Nuttall, Ixodes woodi Bishopp, Dermacentor occidentalis Marx, and Dermacentor parumapertus Neumann), two of which transmit bacterial zoonotic agents to people in the far-western United States. There was no decrease in number of ticks per animal trapped at either burn site compared with controls; in fact, the mean number of immature I. pacificus per rodent was significantly higher at one burn site than its control site. Soil refugia may protect ticks from fire-induced mortality; the argasid tick Ornithodoros coriaceus Koch, which lives in soil, was unaffected by the prescribed fire as were I. pacificus and D. occidentalis buried in packets 2.5 cm below ground. We conclude that although prescribed fires in chaparral habitats may diminish local rodent abundance, it does not decrease tick loads on rodents. Furthermore, burning chaparral does not result in a decreased abundance of adult ixodid ticks on vegetation and apparently does not affect argasid or ixodid ticks that are sheltered within soil refugia.