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1.
Int J Mol Sci ; 25(10)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38791504

RESUMO

Optimal oxygen management during pediatric cardiopulmonary bypass (CPB) is unknown. We previously demonstrated an increase in cortical mitochondrial reactive oxygen species and decreased mitochondrial function after CPB using hyperoxic oxygen management. This study investigates whether controlled oxygenation (normoxia) during CPB reduces cortical mitochondrial dysfunction and oxidative injury. Ten neonatal swine underwent three hours of continuous CPB at 34 °C (flow > 100 mL/kg/min) via cervical cannulation targeting a partial pressure of arterial oxygen (PaO2) goal < 150 mmHg (normoxia, n = 5) or >300 mmHg (hyperoxia, n = 5). The animals underwent continuous hemodynamic monitoring and serial arterial blood sampling. Cortical microdialysate was serially sampled to quantify the glycerol concentration (represents neuronal injury) and lactate-to-pyruvate ratio (represents bioenergetic dysfunction). The cortical tissue was analyzed via high-resolution respirometry to quantify mitochondrial oxygen consumption and reactive oxygen species generation, and cortical oxidized protein carbonyl concentrations were quantified to assess for oxidative damage. Serum PaO2 was higher in hyperoxia animals throughout CPB (p < 0.001). There were no differences in cortical glycerol concentration between groups (p > 0.2). The cortical lactate-to-pyruvate ratio was modestly elevated in hyperoxia animals (p < 0.03) but the values were not clinically significant (<30). There were no differences in cortical mitochondrial respiration (p = 0.48), protein carbonyls (p = 0.74), or reactive oxygen species generation (p = 0.93) between groups. Controlled oxygenation during CPB does not significantly affect cortical mitochondrial function or oxidative injury in the acute setting. Further evaluation of the short and long-term effects of oxygen level titration during pediatric CPB on cortical tissue and other at-risk brain regions are needed, especially in the presence of cyanosis.


Assuntos
Animais Recém-Nascidos , Ponte Cardiopulmonar , Mitocôndrias , Oxigênio , Espécies Reativas de Oxigênio , Animais , Suínos , Ponte Cardiopulmonar/efeitos adversos , Ponte Cardiopulmonar/métodos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Oxigênio/metabolismo , Consumo de Oxigênio , Ácido Láctico/metabolismo , Ácido Láctico/sangue , Estresse Oxidativo , Córtex Cerebral/metabolismo , Ácido Pirúvico/metabolismo , Hiperóxia/metabolismo
2.
World J Pediatr Congenit Heart Surg ; : 21501351241232077, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38646826

RESUMO

Objectives: We previously demonstrated cerebral mitochondrial dysfunction in neonatal swine immediately following a period of full-flow cardiopulmonary bypass (CPB). The extent to which this dysfunction persists in the postoperative period and its correlation with other markers of cerebral bioenergetic failure and injury is unknown. We utilized a neonatal swine model to investigate the early evolution of mitochondrial function and cerebral bioenergetic failure after CPB. Methods: Twenty piglets (mean weight 4.4 ± 0.5 kg) underwent 3 h of CPB at 34 °C via cervical cannulation and were followed for 8, 12, 18, or 24 h (n = 5 per group). Markers of brain tissue damage (glycerol) and bioenergetic dysfunction (lactate to pyruvate ratio) were continuously measured in cerebral microdialysate samples. Control animals (n = 3, mean weight 4.1 ± 1.2 kg) did not undergo cannulation or CPB. Brain tissue was extracted immediately after euthanasia to obtain ex-vivo cortical mitochondrial respiration and frequency of cortical microglial nodules (indicative of cerebral microinfarctions) via neuropathology. Results: Both the lactate to pyruvate ratio (P < .0001) and glycerol levels (P = .01) increased in cerebral microdialysate within 8 h after CPB. At 24 h post-CPB, cortical mitochondrial respiration was significantly decreased compared with controls (P = .046). The presence of microglial nodules increased throughout the study period (24 h) (P = .01, R2 = 0.9). Conclusion: CPB results in impaired cerebral bioenergetics that persist for at least 24 h. During this period of bioenergetic impairment, there may be increased susceptibility to secondary injury related to alterations in metabolic delivery or demand, such as hypoglycemia, seizures, and decreased cerebral blood flow.

3.
Resuscitation ; 191: 109950, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37634859

RESUMO

AIM: Develop a novel, physiology-based measurement of duty cycle (Arterial Blood Pressure-Area Duty Cycle [ABP-ADC]) and evaluate the association of ABP-ADC with intra-arrest hemodynamics and patient outcomes. METHODS: This was a secondary retrospective study of prospectively collected data from the ICU-RESUS trial (NCT02837497). Invasive arterial waveform data were used to derive ABP-ADC. The primary exposure was ABP-ADC group (<30%; 30-35%; >35%). The primary outcome was systolic blood pressure (sBP). Secondary outcomes included intra-arrest physiologic goals, CPR quality targets, and patient outcomes. In an exploratory analysis, adjusted splines and receiver operating characteristic (ROC) curves were used to determine an optimal ABP-ADC associated with improved hemodynamics and outcomes using a multivariable model. RESULTS: Of 1129 CPR events, 273 had evaluable arterial waveform data. Mean age is 2.9 years + 4.9 months. Mean ABP-ADC was 32.5% + 5.0%. In univariable analysis, higher ABP-ADC was associated with lower sBP (p < 0.01) and failing to achieve sBP targets (p < 0.01). Other intra-arrest physiologic parameters, quality metrics, and patient outcomes were similar across ABP-ADC groups. Using spline/ROC analysis and clinical judgement, the optimal ABP-ADC cut point was set at 33%. On multivariable analysis, sBP was significantly higher (point estimate 13.18 mmHg, CI95 5.30-21.07, p < 0.01) among patients with ABP-ADC < 33%. Other intra-arrest physiologic and patient outcomes were similar. CONCLUSIONS: In this multicenter cohort, a lower ABP-ADC was associated with higher sBPs during CPR. Although ABP-ADC was not associated with outcomes, further studies are needed to define the interactions between CPR mechanics and intra arrest patient physiology.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca , Humanos , Pré-Escolar , Pressão Arterial , Estudos Retrospectivos , Parada Cardíaca/terapia , Hemodinâmica/fisiologia , Pressão Sanguínea/fisiologia
4.
Biomedicines ; 11(7)2023 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-37509447

RESUMO

Traumatic brain injury (TBI) results in the generation of tau. As hyperphosphorylated tau (p-tau) is one of the major consequences of TBI, targeting p-tau in TBI may lead to the development of new therapy. Twenty-five pigs underwent a controlled cortical impact. One hour after TBI, pigs were administered either vehicle (n = 13) or PNT001 (n = 12), a monoclonal antibody for the cis conformer of tau phosphorylated at threonine 231. Plasma biomarkers of neural injury were assessed for 14 days. Diffusion tensor imaging was performed at day 1 and 14 after injury, and these were compared to historical control animals (n = 4). The fractional anisotropy data showed significant white matter injury for groups at 1 day after injury in the corona radiata. At 14 days, the vehicle-treated pigs, but not the PNT001-treated animals, exhibited significant white matter injury compared to sham pigs in the ipsilateral corona radiata. The PNT001-treated pigs had significantly lower levels of plasma glial fibrillary acidic protein (GFAP) at day 2 and day 4. These findings demonstrate a subtle reduction in the areas of white matter injury and biomarkers of neurological injury after treatment with PNT001 following TBI. These findings support additional studies for PNT001 as well as the potential use of this agent in clinical trials in the near future.

5.
bioRxiv ; 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37503137

RESUMO

Background: Pediatric neurological injury and disease is a critical public health issue due to increasing rates of survival from primary injuries (e.g., cardiac arrest, traumatic brain injury) and a lack of monitoring technologies and therapeutics for the treatment of secondary neurological injury. Translational, preclinical research facilitates the development of solutions to address this growing issue but is hindered by a lack of available data frameworks and standards for the management, processing, and analysis of multimodal data sets. Methods: Here, we present a generalizable data framework that was implemented for large animal research at the Children's Hospital of Philadelphia to address this technological gap. The presented framework culminates in an interactive dashboard for exploratory analysis and filtered data set download. Results: Compared with existing clinical and preclinical data management solutions, the presented framework accommodates heterogeneous data types (single measure, repeated measures, time series, and imaging), integrates data sets across various experimental models, and facilitates dynamic visualization of integrated data sets. We present a use case of this framework for predictive model development for intra-arrest prediction of cardiopulmonary resuscitation outcome. Conclusions: The described preclinical data framework may serve as a template to aid in data management efforts in other translational research labs that generate heterogeneous data sets and require a dynamic platform that can easily evolve alongside their research.

6.
Biomed Opt Express ; 14(6): 2432-2448, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37342705

RESUMO

In this study, we used diffuse optics to address the need for non-invasive, continuous monitoring of cerebral physiology following traumatic brain injury (TBI). We combined frequency-domain and broadband diffuse optical spectroscopy with diffuse correlation spectroscopy to monitor cerebral oxygen metabolism, cerebral blood volume, and cerebral water content in an established adult swine-model of impact TBI. Cerebral physiology was monitored before and after TBI (up to 14 days post injury). Overall, our results suggest that non-invasive optical monitoring can assess cerebral physiologic impairments post-TBI, including an initial reduction in oxygen metabolism, development of cerebral hemorrhage/hematoma, and brain swelling.

7.
J Neurotrauma ; 40(1-2): 74-85, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35876453

RESUMO

Traumatic brain injury (TBI) causes significant white matter injury, which has been characterized by various rodent and human clinical studies. The exact time course of imaging changes in a pediatric brain after TBI and its relation to biomarkers of injury and cellular function, however, is unknown. To study the changes in major white matter structures using a valid model of TBI that is comparable to a human pediatric brain in terms of size and anatomical features, we utilized a four-week-old pediatric porcine model of injury with controlled cortical impact (CCI). Using diffusion tensor imaging differential tractography, we show progressive anisotropy changes at major white matter tracts such as the corona radiata and inferior fronto-occipital fasciculus between day 1 and day 30 after injury. Moreover, correlational tractography shows a large part of bilateral corona radiata having positive correlation with the markers of cellular respiration. In contrast, bilateral corona radiata has a negative correlation with the plasma biomarkers of injury such as neurofilament light or glial fibrillary acidic protein. These are expected correlational findings given that higher integrity of white matter would be expected to correlate with lower injury biomarkers. We then studied the magnetic resonance spectroscopy findings and report decrease in a N-acetylaspartate/creatinine (NAA/Cr) ratio at the pericontusional cortex, subcortical white matter, corona radiata, thalamus, genu, and splenium of corpus callosum at 30 days indicating injury. There was also an increase in choline/creatinine ratio in these regions indicating rapid membrane turnover. Given the need for a pediatric TBI model that is comparable to human pediatric TBI, these data support the use of a pediatric pig model with CCI in future investigations of therapeutic agents. This model will allow future TBI researchers to rapidly translate our pre-clinical study findings into clinical trials for pediatric TBI.


Assuntos
Lesões Encefálicas Traumáticas , Substância Branca , Animais , Criança , Humanos , Anisotropia , Biomarcadores/análise , Biomarcadores/sangue , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Creatinina/sangue , Imagem de Tensor de Difusão/métodos , Suínos , Substância Branca/diagnóstico por imagem
8.
J Environ Manage ; 224: 406-413, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30071452

RESUMO

Saline wastewater is a by-product of cheese manufacturing and whey processing that can have serious environmental and economic consequences. Salty streams originating from dairy processing operations include chromatography wastes, clean-in-place wastewater, acid whey, salty whey and waste generated from whey demineralization processes such as nanofiltration, electrodialysis and ion exchange. With the participation of the major dairy companies in Australia, an industry wide survey was conducted to acquire a comprehensive understanding of the management strategies for these salty waste streams. High salinity waste streams are commonly directed to evaporation ponds. However, environmental impacts from land degradation, odour and dust have prevented the construction of further evaporation ponds in some areas of Australia. The survey results also show that disposal to municipal trade waste is not always effective, as the current levels of some salinity-related parameters are significantly higher than the levels allowed by the local water/environmental authorities. For high salinity streams, salt removal can lead to more substantial savings in trade waste charges compared to wastewater volume reduction. Thus, salt removal and recovery from salty waste streams has become a major focus of the sustainability agenda of the Australian dairy industry.


Assuntos
Indústria de Laticínios , Gerenciamento de Resíduos , Austrália , Queijo , Eliminação de Resíduos Líquidos , Águas Residuárias
9.
Occup Med (Lond) ; 68(1): 32-37, 2018 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-29361061

RESUMO

Background: Military personnel may be exposed to hazardous substances or environments, making health surveillance critical. However, surveillance is frequently handicapped by long lag times between exposure(s) and outcomes, which often manifest post-military release and are often not recorded. Aims: To describe the burden of mortality in still serving and released Canadian Armed Forces (CAF) personnel. Methods: The Canadian Forces Cancer and Mortality Study II (CF CAMS II) is an interdepartmental record linkage study using CAF pay data and Statistics Canada cancer and mortality data. The cohort included all Regular Force and class C Reservist men and women who first enrolled in the CAF between 1976 and 2012, inclusive. The anonymized linked data included death data, including cause and location of death. All-cause mortality (ACM) and International Classification of Disease (ICD)-10 chapter-level mortality (CLM) were quantified using standardized mortality ratios (SMRs), with the Canadian general population (CGP) as the reference population. Results: Approximately 6870 deaths occurred during over 5 million person-years of observations. For ACM, the CAF risk of death was significantly lower than the CGP for both sexes (females: n = 540, SMR = 0.76 [95% CI 0.69-0.82]; males: n = 6330, SMR = 0.79 [95% CI 0.77-0.81]). In the CLM analysis, SMRs were significantly lower than, or not statistically different from, 1.0 for all ICD chapters. Conclusions: Military service may have a protective effect that may be partly explained by the healthy soldier effect and the stringent selection process at enrolment.


Assuntos
Militares/estatística & dados numéricos , Mortalidade/tendências , Adulto , Idoso , Canadá/epidemiologia , Canadá/etnologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/etnologia
10.
Water Res ; 101: 300-308, 2016 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-27267478

RESUMO

An understanding of crystallisation within saline effluents is important for the design of both brine crystallisers and brine disposal ponds. In this work, crystallisation of a saline effluent concentrate from the Australian dairy industry has been examined at 22 wt% and 30 wt% total solids and at temperatures between 10 and 70 °C. The precipitation occurs more rapidly at higher temperatures. This trend is dictated by precipitation of calcium phosphate salts, albeit the major constituents of the mixture are NaCl and lactose. The crystallisation induction time can be shortened by introducing cavitation induced by ultrasound. In particular, the use of two short acoustic pulses between 3.7 J/g and 16 J/g at 20 kHz spaced ten minutes apart has maximum impact upon both induction time and crystal size. It is believed that the first ultrasound pulse either generates new nuclei or enhances the mass transfer of solute toward the surface of sub-micron growing crystals. Conversely, the second pulse disrupts the growing crystals and forms secondary nuclei. The ultrasound cannot shift the solution equilibrium and so is not able to improve the low crystal yield. To increase this total yield, further evaporation is necessary. The work provides direction to personnel in the dairy industry of the feasibility of brine crystallisation with respect to energy demand and solid recovery.


Assuntos
Cristalização , Cloreto de Sódio , Minerais , Soluções , Temperatura
11.
Rev Sci Instrum ; 87(5): 056108, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27250483

RESUMO

A novel home-built system for imaging cold atom samples is presented using a readily available astronomy camera which has the requisite sensitivity but no timing-control. We integrate the camera with LabVIEW achieving fast, low-jitter imaging with a convenient user-defined interface. We show that our system takes precisely timed millisecond exposures and offers significant improvements in terms of system jitter and readout time over previously reported home-built systems. Our system rivals current commercial "black box" systems in performance and user-friendliness.

12.
Psychol Med ; 45(15): 3239-48, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26169730

RESUMO

BACKGROUND: The objective of this study was to examine associations between trajectories of childhood neighbourhood social cohesion and adolescent mental health and behaviour. METHOD: This study used data from the National Longitudinal Survey of Children and Youth, a nationally representative sample of Canadian children. The sample included 5577 children aged 0-3 years in 1994-1995, prospectively followed until age 12-15 years. Parental perceived neighbourhood cohesion was assessed every 2 years. Latent growth class modelling was used to identify trajectories of neighbourhood cohesion. Mental health and behavioural outcomes were self-reported at age 12-15 years. Logistic regression was used to examine associations between neighbourhood cohesion trajectories and outcomes, adjusting for potential confounders. RESULTS: Five distinct trajectories were identified: 'stable low' (4.2%); 'moderate increasing' (9.1%); 'stable moderate' (68.5%); 'high falling' (8.9%); and 'stable high' (9.3%). Relative to those living in stable moderately cohesive neighbourhoods, those in stable low cohesive neighbourhoods were more likely to experience symptoms of anxiety/depression [odds ratio (OR) = 1.73, 95% confidence interval (CI) 1.04-2.90] and engage in indirect aggression (OR = 1.62, 95% CI 1.07-2.45). Those with improvements in neighbourhood cohesion had significantly lower odds of hyperactivity (OR = 0.67, 95% CI 0.46-0.98) and indirect aggression (OR = 0.69, 95% CI 0.49-0.96). In contrast, those with a decline in neighbourhood cohesion had increased odds of hyperactivity (OR = 1.67, 95% CI 1.21-2.29). Those in highly cohesive neighbourhoods in early childhood were more likely to engage in prosocial behaviour ('high falling': OR = 1.93, 95% CI 1.38-2.69; 'stable high': OR = 1.89, 95% CI 1.35-2.63). CONCLUSIONS: These results suggest that neighbourhood cohesion in childhood may have time-sensitive effects on several domains of adolescent mental health and behaviour.


Assuntos
Comportamento do Adolescente/psicologia , Ansiedade/psicologia , Depressão/psicologia , Comportamento Problema/psicologia , Características de Residência , Adolescente , Comportamento do Adolescente/classificação , Canadá , Criança , Pré-Escolar , Feminino , Inquéritos Epidemiológicos , Humanos , Lactente , Estudos Longitudinais , Masculino
13.
Psychol Med ; 44(13): 2845-54, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25066933

RESUMO

BACKGROUND: The aetiology of depression is multifactorial, with biological, cognitive and environmental factors across the life course influencing risk of a depressive episode. There is inconsistent evidence linking early life development and later depression. The aim of this study was to investigate relationships between low birthweight (LBW), infant neurodevelopment, and acute and chronic stress as components in pathways to depression in adulthood. METHOD: The sample included 4627 members of the National Survey of Health and Development (NSHD; the 1946 British birth cohort). Weight at birth, age of developmental milestones, economic deprivation in early childhood, acute stressors in childhood and adulthood, and socio-economic status (SES) in adulthood were assessed for their direct and indirect effects on adolescent (ages 13 and 15 years) and adult (ages 36, 43 and 53 years) measures of depressive symptoms in a structural equation modelling (SEM) framework. A structural equation model developed to incorporate all variables exhibited excellent model fit according to several indices. RESULTS: The path of prediction from birthweight to age of developmental milestones to adolescent depression/anxiety to adult depression/anxiety was significant (p < 0.001). Notably, direct paths from birthweight (p = 0.25) and age of developmental milestones (p = 0.23) to adult depression were not significant. Childhood deprivation and stressors had important direct and indirect effects on depression. Stressors in adulthood were strongly associated with adult depression. CONCLUSIONS: Depression in adulthood is influenced by an accumulation of stressors across the life course, including many that originate in the first years of life. Effects of early-life development on mental health appear by adolescence.


Assuntos
Depressão/fisiopatologia , Desenvolvimento Humano/fisiologia , Recém-Nascido de Baixo Peso/fisiologia , Estresse Psicológico/fisiopatologia , Adolescente , Adulto , Pré-Escolar , Depressão/epidemiologia , Depressão/etiologia , Feminino , Humanos , Recém-Nascido , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estresse Psicológico/complicações , Estresse Psicológico/epidemiologia , Reino Unido/epidemiologia
14.
Int J Proteomics ; 2014: 572901, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24987528

RESUMO

Over 230 serovars of Leptospira interrogans have been identified; however few have been completely characterised. The aim of this study was to characterise the proteome of serovar Canicola and to compare this against the serovars of Copenhageni and Pomona. 2D-LC/MS analysis identified 1653 Leptospira proteins in serovar Canicola; 60 of these proteins were common to Copenhageni and Pomona, 16 of which are known to be immunogenic. This study provides the first reported proteome for serovar Canicola and suggests that proteomic comparison of different serovars could be used as a tool for identification of novel target molecules for vaccine development.

15.
Clin Vaccine Immunol ; 21(4): 546-51, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24521782

RESUMO

The Leptospira interrogans vaccines currently available are serovar specific and require regular booster immunizations to maintain protection of the host. In addition, a hamster challenge batch potency test is necessary to evaluate these vaccines prior to market release, requiring the use of a large number of animals, which is ethically and financially undesirable. Our previous work showed that the N terminus of the outer membrane protein LipL32 was altered in Leptospira interrogans serovar Canicola vaccines that fail the hamster challenge test, suggesting that it may be involved in the protective immune response. The aim of this study was to determine if vaccination with LipL32 protein alone could provide a protective response against challenge with L. interrogans serovar Canicola to hamsters. Recombinant LipL32, purified from an Escherichia coli expression system, was assessed for protective immunity in five groups of hamsters (n = 5) following a challenge with the virulent L. interrogans serovar Canicola strain Kito as a challenge strain. However, no significant survival against the L. interrogans serovar Canicola challenge was observed compared to that of unvaccinated negative controls. Subsequent histological analysis revealed reduced amounts of L. interrogans in the kidneys from the hamsters vaccinated with recombinant LipL32 protein prior to challenge; however, no significant survival against the L. interrogans serovar Canicola challenge was observed compared to that of unvaccinated negative controls. This finding corresponded to a noticeably reduced severity of renal lesions. This study provides evidence that LipL32 is involved in the protective response against L. interrogans serovar Canicola in hamsters and is the first reported link to LipL32-induced protection against kidney invasion.


Assuntos
Carga Bacteriana , Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas/imunologia , Rim/microbiologia , Leptospira interrogans serovar canicola/imunologia , Leptospirose/prevenção & controle , Lipoproteínas/imunologia , Vacinação/métodos , Animais , Proteínas da Membrana Bacteriana Externa/administração & dosagem , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/isolamento & purificação , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/genética , Cricetinae , Modelos Animais de Doenças , Escherichia coli/genética , Feminino , Expressão Gênica , Histocitoquímica , Leptospira interrogans serovar canicola/isolamento & purificação , Leptospirose/imunologia , Leptospirose/microbiologia , Leptospirose/patologia , Lipoproteínas/administração & dosagem , Lipoproteínas/genética , Lipoproteínas/isolamento & purificação , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Análise de Sobrevida , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
16.
J Affect Disord ; 152-154: 139-45, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24206929

RESUMO

BACKGROUND: Childhood cognitive ability may have protective effects against internalizing symptoms in adolescence, although this may depend on the time of symptom assessment and child gender. Also, the effects of childhood stressors on adolescent internalizing symptoms may be moderated by childhood cognitive ability. METHODS: The sample included 4405 individuals from the Canadian National Longitudinal Study of Children and Youth (NLSCY). Between ages 4-5 and 10-11, children completed a test of verbal ability and scholastic aptitude and a series of mathematics computation tests. Internalizing symptoms were assessed via self-reports at ages 12-13 and 14-15. RESULTS: Greater cognitive ability was generally associated with decreased odds of internalizing symptoms at age 12-13. However, greater cognitive ability generally increased, or had no effect on, the odds of internalizing symptoms at age 14-15. Some of the effects of childhood cognitive ability varied with child gender. Also, childhood cognitive ability attenuated the effects of family dysfunction and chronic illness throughout childhood on subsequent internalizing symptoms. LIMITATIONS: These data are largely subject to some degree of reporting bias, the tests of cognitive ability are limited and may not represent overall cognitive ability, and there may be intermediary variables that account for the relationship between childhood cognitive ability and adolescent internalizing symptoms. CONCLUSION: Results suggest that programs attempting to increase early cognitive skills may be particularly beneficial for girls. Also, an increased focus on cognitive skills may attenuate the negative effects of some stressors on subsequent anxious and depressive symptoms, regardless of child gender.


Assuntos
Ansiedade/psicologia , Aptidão , Cognição , Depressão/psicologia , Adolescente , Fatores Etários , Ansiedade/epidemiologia , Ansiedade/etiologia , Testes de Aptidão , Canadá/epidemiologia , Criança , Pré-Escolar , Depressão/epidemiologia , Depressão/etiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Testes Psicológicos , Análise de Regressão , Fatores de Risco , Fatores Sexuais , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia
17.
Health Educ Res ; 28(3): 375-91, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23660461

RESUMO

The most effective woman-initiated method to prevent HIV/sexually transmitted infections is the female condom (FC). Yet, FCs are often difficult to find and denigrated or ignored by community health and service providers. Evidence increasingly supports the need to develop and test theoretically driven, multilevel interventions using a community-empowerment framework to promote FCs in a sustained way. We conducted a study in a midsized northeastern US city (2009-2013) designed to create, mobilize and build capacity of a community group to develop and implement multilevel interventions to increase availability, accessibility and support for FCs in their city. The Community Action and Advocacy Board (CAAB) designed and piloted interventions concurrently targeting community, organizational and individual levels. Ethnographic observation of the CAAB training and intervention planning and pilot implementation sessions documented the process, preliminary successes, challenges and limitations of this model. The CAAB demonstrated ability to conceptualize, plan and initiate multilevel community change. However, challenges in group decision-making and limitations in members' availability or personal capacity constrained CAAB processes and intervention implementation. Lessons from this experience could inform similar efforts to mobilize, engage and build capacity of community coalitions to increase access to and support for FCs and other novel effective prevention options for at-risk women.


Assuntos
Participação da Comunidade , Preservativos Femininos , Defesa do Paciente , Participação da Comunidade/métodos , Preservativos Femininos/estatística & dados numéricos , Preservativos Femininos/provisão & distribuição , Feminino , Humanos , Meio-Oeste dos Estados Unidos , Estudos de Casos Organizacionais
18.
Clin Vaccine Immunol ; 19(4): 587-93, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22323560

RESUMO

The current batch potency test for Leptospira interrogans serovar Canicola vaccines requires the use of a large number of hamsters and has severe effects (i.e., hepatic and renal failure resulting in death); while this vaccine is effective, a safer, cheaper, more ethical replacement is desired. The aim of this study was to analyze vaccine proteomes and identify target molecules common to all L. interrogans serovar Canicola vaccines which could be used to design an in vitro potency test. Initial analysis of L. interrogans serovar Canicola vaccines (A to E) from different manufacturers, using the Limulus amebocyte lysate assay and silver-stained sodium dodecyl sulfate polyacrylamide gels, indicated that lipopolysaccharide was not present in all vaccines, preventing it from being a suitable target molecule. The protein contents of vaccines A to E were therefore determined by two-dimensional liquid chromatography mass spectrometry ([2D-LC/MS] 221 ± 31, 9 ± 8, 34 ± 4, 21 ± 5, and 34 ± 17 proteins [mean ± 1 standard deviation] found, respectively). The outer membrane protein LipL32 was established to be common to all and to be present at a significantly higher (P ≤ 0.05) relative spectral abundance in a batch of vaccine which passed the in vivo potency test than in one which had failed. Further analysis using multiple reaction monitoring revealed that the concentration of the N terminus of LipL32 was significantly lower (P ≤ 0.01) in failed batches (n = 2) of vaccine than in passed batches (n = 2); the concentration of the C terminus between the two batches was approximately the same. An in vitro Leptospira vaccine potency test, based on N-terminal amino acid quantification of LipL32, was subsequently developed.


Assuntos
Anticorpos Antibacterianos/sangue , Proteínas da Membrana Bacteriana Externa/análise , Vacinas Bacterianas/química , Vacinas Bacterianas/imunologia , Leptospira interrogans serovar canicola/química , Leptospira interrogans serovar canicola/imunologia , Lipoproteínas/análise , Tecnologia Farmacêutica/métodos , Animais , Proteínas de Bactérias/análise , Biomarcadores/análise , Cromatografia Líquida , Cricetinae , Eletroforese em Gel Bidimensional , Feminino , Espectrometria de Massas , Proteoma/análise
19.
Public Health ; 125(5): 283-92, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21513961

RESUMO

OBJECTIVES: To describe female condom (FC) use, male condom (MC) use and overall levels of protected sex before, during and after FC education and promotion (using the original prototype FC) combined with MC promotion among female sex workers in three rural or small urban settings in southern China. STUDY DESIGN: The 1-year FC intervention was conducted by local health workers through outreach to establishments where sex work is conducted. Three serial cross-sectional surveys were conducted in each study town before, during and after the intervention along with process documentation throughout the intervention period. METHODS: Cross-sectional data from pre-intervention (baseline) and 6-month and 12-month post-intervention surveys from three study sites are used in a descriptive comparison of the context of the sex industry, outreach in two phases of intervention, and FC adoption after the intensive intervention phase in each site. RESULTS: Approximately 75-80% of eligible women working in sex establishments, varying from 74 to 155 participants for each survey, were recruited from three study sites. After introduction and promotion of the FC along with the MC during the community public health intervention, between one-fifth and one-half of the study participants had tried the FC in the three study sites by the time of the 6-month and 12-month cross-sectional surveys. Among them, 10-30% had used the FC more than once. FC awareness increased following the intervention with much less variation across the three study sites. At baseline, 31-54% of participants across the three sites reported 100% protected sex in the last 30 days with all types of partners. At one of the sites with relatively low MC use before the intervention, the proportion of women reporting 100% protected sex in the last 30 days increased by 15%, and the proportion reporting nil protected sex in the last 30 days decreased by 13% between baseline and 12-month post-intervention surveys. More complex profiles of FC and MC use and protected sex were shown at the other two study sites, where a higher level of protection had been reached before the project started. CONCLUSIONS: Different levels of FC adoption were identified after the 1-year FC promotion intervention through outreach to sex establishments. The input, output and outcomes of the intervention may be associated with women's demographic and risk characteristics, the local capacities of intervention staff, and other contextual factors. Further analysis of these factors will help establish the role of the FC in increasing protected sex, and provide insight into how to achieve greater FC use.


Assuntos
Preservativos Femininos/estatística & dados numéricos , Infecções por HIV/prevenção & controle , Trabalho Sexual , Infecções Sexualmente Transmissíveis/prevenção & controle , Adolescente , Adulto , Preservativos/estatística & dados numéricos , Estudos Transversais , Coleta de Dados , Feminino , Promoção da Saúde , Humanos , Pessoa de Meia-Idade , População Rural , População Urbana , Adulto Jovem
20.
Osteoarthritis Cartilage ; 15(10): 1134-40, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17543548

RESUMO

OBJECTIVE: To assess characteristics of active motor units (MUs) during volitional vastus medialis (VM) activation in adults with symptomatic knee osteoarthritis (OA) across the spectrum of radiographic severity and age-comparable healthy control volunteers. METHODS: We evaluated 39 participants (age 65+/-3 years) in whom weight-bearing knee X-rays were assigned a Kellgren & Lawrence (KL) grade (18 with KL grade=0; four each with KL grades=1, 2 and 4; nine with grade 3). Electromyography (EMG) signals were simultaneously acquired using surface [surface EMG (S-EMG)] and intramuscular needle electrodes, and analyzed by decomposition-enhanced spike-triggered averaging to obtain estimates of size [surface-represented MU action potentials (S-MUAP) area], number [MU recruitment index (MURI)] and firing rates [MU firing rates (mFR)] of active MUs at 10%, 20%, 30% and 50% effort relative to maximum voluntary force [maximal voluntary isometric contraction (MVIC)] during isometric knee extension. RESULTS: Knee extensor MVIC was lower in OA participants, especially at higher KL grades (P=0.05). Taking the observed force differences into account, OA was also associated with activation of larger MUs (S-MUAP area/MVICx%effort; P<0.0001). In contrast, the estimated number of active units (MURI/MVICx%effort) changed differently as effort increased from 10% to 50% and was higher with advanced OA (KL=3, 4) than controls (P=0.0002). CONCLUSION: VM activation changes at the level of the MU with symptomatic knee OA, and this change is influenced by radiographic severity. Poor muscle quality may explain the pattern observed with higher KL grades, but alternative factors (e.g., nerve or joint injury, physical inactivity or muscle composition changes) should be examined in early OA.


Assuntos
Articulação do Joelho/fisiopatologia , Neurônios Motores/fisiologia , Osteoartrite do Joelho/fisiopatologia , Músculo Quadríceps/fisiologia , Fatores Etários , Idoso , Estudos de Casos e Controles , Eletromiografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Limitação da Mobilidade , Análise de Regressão
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