Effects of anesthesia on functional activation of cerebral blood flow and metabolism

Functional brain mapping based on changes in local cerebral blood flow (lCBF) or glucose utilization (lCMRglc) induced by functional activation is generally carried out in animals under anesthesia, usually α-chloralose because of its lesser effects on cardiovascular, respiratory, and reflex functions. Results of studies on the role of nitric oxide (NO) in the mechanism of functional activation of lCBF have differed in unanesthetized and anesthetized animals. NO synthase inhibition markedly attenuates or eliminates the lCBF responses in anesthetized animals but not in unanesthetized animals. The present study examines in conscious rats and rats anesthetized with α-chloralose the effects of vibrissal stimulation on lCMRglc and lCBF in the whisker-to-barrel cortex pathway and on the effects of NO synthase inhibition with NG-nitro-l-arginine methyl ester (l-NAME) on the magnitude of the responses. Anesthesia markedly reduced the lCBF and lCMRglc responses in the ventral posteromedial thalamic nucleus and barrel cortex but not in the spinal and principal trigeminal nuclei. l-NAME did not alter the lCBF responses in any of the structures of the pathway in the unanesthetized rats and also not in the trigeminal nuclei of the anesthetized rats. In the thalamus and sensory cortex of the anesthetized rats, where the lCBF responses to stimulation had already been drastically diminished by the anesthesia, l-NAME treatment resulted in loss of statistically significant activation of lCBF by vibrissal stimulation. These results indicate that NO does not mediate functional activation of lCBF under physiological conditions.

Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain.

The hypothesis that age-associated impairment of cognitive and motor functions is due to oxidative molecular damage was tested in the mouse. In a blind study, senescent mice (aged 22 months) were subjected to a battery of behavioral tests for motor and cognitive functions and subsequently assayed for oxidative molecular damage as assessed by protein carbonyl concentration in different regions of the brain. The degree of age-related impairment in each mouse was determined by comparison to a reference group of young mice (aged 4 months) tested concurrently on the behavioral battery. The age-related loss of ability to perform a spatial swim maze task was found to be positively correlated with oxidative molecular damage in the cerebral cortex, whereas age-related loss of motor coordination was correlated with oxidative molecular damage within the cerebellum. These results support the view that oxidative stress is a causal factor in brain senescence. Furthermore, the findings suggest that age-related declines of cognitive and motor performance progress independently, and involve oxidative molecular damage within different regions of the brain.

Efeitos dos agrotóxicos Kraft®36EC e Score®250EC (e seus princípios ativos) em ecossistemas aquáticos: análises comparativas e ecossistêmicas

Com o advento da agricultura ampliou-se a produção alimentar e os bens de consumo, no entanto, os riscos ambientais também foram maximizados em função da adoção de técnicas produtivas baseadas no uso intensivo de insumos agrícolas. Esta problemática é mundial, embora mais evidenciada nos países em desenvolvimento e que tem, na produção agrícola, a base de sua economia. O Brasil enquadra-se nesta situação e desde 2009 é considerado o maior consumidor de agrotóxicos do mundo, criando um cenário de risco ambiental e de saúde humana. Os efeitos ambientais, base deste estudo, estão relacionados não somente à perda de espécies não-alvo, uma vez que os agrotóxicos não são seletivos, mas também as alterações em nível ecossistêmico, a qual se relaciona com as perdas das funções e dos serviços gerados pelos sistemas naturais. Adiciona-se a esta complexidade, a forma de ação de cada agrotóxico, a distribuição dos mesmos nos diferentes compartimentos (ar, solo e água), o período de permanência de cada um, as relações sinérgicas decorrentes das interações entre diferentes produtos, a formação de subprodutos no processo de degradação, entre outros fatores, como as diferenças existentes entre o ingrediente ativo e a formulação comercial, na qual existem os chamados ingredientes inertes em sua composição, os quais podem ser muito mais tóxicos para espécies e ecossistemas. Considerando esta abordagem, a presente pesquisa foi desenvolvida com base na realidade de um local de referência, o município de Bom Repouso (MG/BR), no qual a intensificação da produção de morango e batata tem trazido uma série de riscos sociais e ambientais. Semelhante a outras regiões produtivas do país, o uso de agrotóxicos é recorrente, amplo e irrestrito, com destaque para as formulações comerciais Kraft®36EC e Score®250EC, as quais, juntamente com seus respectivos ingredientes ativos (abamectina e difenoconazol), foram avaliadas por meio de testes de toxicidade com espécies de diferentes níveis tróficos representativas de um ecossistema aquático, gerando informações que foram avaliadas em nível de espécie e de ecossistema, simulando o cenário de aplicação dos produtos no local de referência. Os resultados obtidos permitiram concluir sobre as diferenças de sensibilidade das espécies e quais seriam as mais indicadas para se avaliar os efeitos tóxicos de ambos os agrotóxicos; os efeitos diferenciados entre a formulação comercial e os ingredientes ativos; bem como as respostas em termos de espécies e de ecossistemas, demonstrando a necessidade de que ambas as análises sejam consideradas na avaliação de risco ecológico.

Loss of Outer Retinal Neurons and Circuitry Alterations in the DBA/2J Mouse

Purpose. The DBA/2J mouse line develops essential iris atrophy, pigment dispersion, and glaucomatous age-related changes, including an increase of IOP, optic nerve atrophy, and retinal ganglion cell (RGC) death. The aim of this study was to evaluate possible morphological changes in the outer retina of the DBA/2J mouse concomitant with disease progression and aging, based on the reduction of both the a- and b-waves and photopic flicker ERGs in this mouse line. Methods. Vertically sectioned DBA/2J mice retinas were evaluated at 3, 8, and 16 months of age using photoreceptor, horizontal, and bipolar cell markers. Sixteen-month-old C57BL/6 mice retinas were used as controls. Results. The DBA/2J mice had outer retinal degeneration at all ages, with the most severe degeneration in the oldest retinas. At 3 months of age, the number of photoreceptor cells and the thickness of the OPL were reduced. In addition, there was a loss of horizontal and ON-bipolar cell processes. At 8 months of age, RGC degeneration occurred in patches, and in the outer retina overlying these patches, cone morphology was impaired with a reduction in size as well as loss of outer segments and growth of horizontal and bipolar cell processes into the outer nuclear layer. At 16 months of age, connectivity between photoreceptors and horizontal and bipolar cell processes overlying these patches was lost. Conclusions. Retinal degeneration in DBA/2J mice includes photoreceptor death, loss of bipolar and horizontal cell processes, and loss of synaptic contacts in an aging-dependent manner.

Behaviours, Processes and Probabilistic Environmental Functions in H-Open Systems

The Patten’s Theory of the Environment, supposes an impotent contribution to the Theoretical Ecology. The hypothesis of the duality of environments, the creaon and genon functions and the three developed propositions are so much of great importance in the field of the Applied Mathematical as Ecology. The authors have undertaken an amplification and revision of this theory, developing the following steps: 1) A theory of processes. 2) A definition of structural and behavioural functions. 3) A probabilistic definition of the environmental functions. In this paper the authors develop the theory of behavioural functions, begin the theory of environmental functions and give a complementary focus to the theory of processes that has been developed in precedent papers.

Social Support Networks and Self-Efficacy of Peruvian Women Diagnosed with Cancer: A Biocultural Analysis of Health Behavior Constructs

Thesis (Ph.D.)--University of Washington, 2016-06

Gene-environment interactions between adult lead exposure and Apolipoprotein E4 on adult hippocampal neurogenesis and cognitive behavior in mice

Thesis (Ph.D.)--University of Washington, 2016-06

HIV Status and Risk Factors for Hypertension in South African Adults

Thesis (Master's)--University of Washington, 2016-06

Antidepressant Use and Risk of Dementia and Cognitive Decline

Thesis (Ph.D.)--University of Washington, 2016-06

Double-strand break repair gene polymorphisms and risk of breast or ovarian cancer

Deficiencies in DNA repair have been hypothesized to increase cancer risk and excess cancer incidence is a feature of inherited diseases caused by defects in DNA damage recognition and repair. We investigated, using a case-control design, whether the double-strand break repair gene polymorphisms RAD51 5' untranslated region -135 G > C, XRCC2 R188H G > A, and XRCC3 T241M C > T were associated with risk of breast or ovarian cancer in Australian women. Sample sets included 1,456 breast cancer cases and 793 age-matched controls ages under 60 years of age, 549 incident ovarian cancer cases, and 335 controls of similar age distribution. For the total sample and the subsample of Caucasian women, there were no significant differences in genotype distribution between breast cancer cases and controls or between ovarian cancer cases and combined control groups. The crude odds ratios (OR) and 95% confidence intervals (95% CI) associated with the RAD51 GC/CC genotype frequency was OR, 1.10; 95% CI, 0.80-1.41 for breast cancer and OR, 1.22; 95% CI, 0.92-1.62 for ovarian cancer. Similarly, there were no increased risks associated with the XRCC2 GA/AA genotype (OR, 0.98; 95% CI, 0.76-1.26 for breast cancer and OR, 0.93; 95% CI, 0.69-1.25 for ovarian cancer) or the XRCC3 CT/TT genotype (OR, 0.92; 95% Cl, 0.77-1.10 for breast cancer and OR, 0.87; 95% CI, 0.71-1.08 for ovarian cancer). Results were little changed after adjustment for age and other measured risk factors. Although there was little statistical power to detect modest increases in risk for the homozygote variant genotypes, particularly for the rare RAD51 and XRCC2 variants, the data suggest that none of these variants play a major role in the etiology of breast or ovarian cancer.

Polymorphisms in glutathione S-transferases and non-melanoma skin cancer risk in Australian renal transplant recipients

Caucasian renal transplant recipients from Queensland, Australia have the highest non-melanoma skin cancer (NMSC) risk worldwide. Although ultraviolet light (UVR) exposure is critical, genetic factors also appear important. We and others have shown that polymorphism in the glutathione S-transferases (GST) is associated with NMSC in UK recipients. However, the effect of high UVR exposure and differences in immunosuppressive regimen on these associations is unknown. In this study, we examined allelism in GSTM1, GSTM3, GSTT1 and GSTP1 in 361 Queensland renal transplant recipients. Data on squamous (SCC) and basal cell carcinoma (BCC), UVR/tobacco exposure and genotype were obtained. Associations with both NMSC risk and numbers were examined using logistic and negative binomial regression, respectively. In the total group, GSTM1 AB [P = 0.049, rate ratio (RR) = 0.23] and GSTM3 AA (P = 0.015, RR = 0.50) were associated with fewer SCC. Recipients were then stratified by prednisolone dose (less than or equal to7 versus >7 mg/day). In the low-dose group, GSTT1 null (P = 0.006, RR = 0.20) and GSTP1 Val/Val (P = 0.021, RR = 0.20) were associated with SCC numbers. In contrast, in the high-dose group, GSTM1 AB (P = 0.009, RR = 0.05), GSTM3 AB (P = 0.042, RR = 2.29) and BB (P = 0.014, RR = 5.31) and GSTP1 Val/Val (P = 0.036, RR = 2.98) were associated with SCC numbers. GSTM1 AB (P = 0.016) and GSTP1 Val/Val (P = 0.046) were also associated with fewer BCC in this group. GSTP1 associations were strongest in recipients with lower UVR/tobacco exposure. The data confirm our UK findings, suggesting that protection against UVR-induced oxidative stress is important in NMSC development in recipients, but that this effect depends on the immunosuppressant regimen.

Genetic diversity and regional identity in the Australian remnant Nothofagus moorei

Nothofagus moorei (F. Muell.) Krasser has a disjunct and narrow distribution in south-eastern Australian cool temperate rainforest. To assess the conservation-genetic priorities for this species, the genetic diversity of 20 populations sampled from the largest remnant patches at northern and southern distributional extremes, the McPherson and Barrington ranges (a total of 146 individuals), was investigated by using inter simple sequence repeats (ISSR). Regeneration in northern regions of N. moorei has been documented to be predominantly by vegetative means, but our results indicate little evidence of clonality outside the multi-stemmed rings of trees. In addition, genetic diversity was considerably higher in the northern (McPherson, h = 0.1613) than in the southern range (Barrington, h = 0.1159), and genetic differentiation was significantly positively correlated with geographic distance in the former region, but not the latter. Total intraspecific variation was moderate, as measured by Shannon's diversity index, I = 0.2719, and Nei's gene diversity, h = 0.1672, and is considered at the high end of spectrum for estimates of narrow endemic species. An analysis of molecular variation indicated that the majority of genetic variation is partitioned among individuals within population (60%; P < 0.001), rather than among populations within regions (10%; P < 0.001). However, a large and significant component of the measured diversity was partitioned between northern and southern regions (29%; P < 0.001). Several hypotheses are outlined to explain these differences and management implications are discussed. However, given the narrow range, poor dispersal mechanism and restriction to cool temperate rainforest, the continued existence of N. moorei is most threatened by environmental instability and habitat loss resulting from global climate change. In this context the northern regions of the species are most at risk and extinction of such populations would lead to a significant loss of genetic variation for the species as a whole.

Conditional risk, return and contagion in the banking sector in Asia

This paper investigates risk and return in the banking sector in three Asian markets of Taiwan, China and Hong Kong. The study focuses on the risk-return relation in a conditional factor GARCH-M framework that controls for time-series effects. The factor approach is adopted to incorporate intra-industry contagion and an analysis of spillovers between large banks and small banks. Finally, the study provides evidence on these relations before and after the Asian financial crisis of 1997. The results are generally consistent across the markets and with expectations.

Disorders of breathing and continence have a stronger association with back pain than obesity and physical activity

Although obesity and physical activity have been argued to predict back pain, these factors are also related to incontinence and breathing difficulties. Breathing and continence mechanisms may interfere with the physiology of spinal control, and may provide a link to back pain. The aim of this study was to establish the association between back pain and disorders of continence and respiration in women. We conducted a cross-sectional analysis of self-report, postal survey data from the Australian Longitudinal Study on Women's Health. We used multinomial logistic regression to model four levels of back pain in relation to both the traditional risk factors of body mass index and activity level, and the potential risk factors of incontinence, breathing difficulties, and allergy. A total of 38 050 women were included from three age-cohorts. When incontinence and breathing difficulties were considered, obesity and physical activity were not consistently associated with back pain. In contrast, odds ratios (OR) for often having back pain were higher for women often having incontinence compared to women without incontinence (OR were 2.5, 2.3 and 2.3 for young, mid-age! and older women, respectively). Similarly, mid-aged and older women had higher odds of having back pain often when they experienced breathing difficulties often compared to women with no breathing problems (OR of 2.0 and 1.9, respectively). Unlike obesity and physical activity, disorders of continence and respiration were strongly related to frequent back pain. This relationship may be explained by physiological limitations of co-ordination of postural, respiratory and continence functions of trunk muscles.

Science-policy in environmental and health risk assessment: if we cannot do without, can we do better?

How can empirical evidence of adverse effects from exposure to noxious agents, which is often incomplete and uncertain, be used most appropriately to protect human health? We examine several important questions on the best uses of empirical evidence in regulatory risk management decision-making raised by the US Environmental Protection Agency (EPA)'s science-policy concerning uncertainty and variability in human health risk assessment. In our view, the US EPA (and other agencies that have adopted similar views of risk management) can often improve decision-making by decreasing reliance on default values and assumptions, particularly when causation is uncertain. This can be achieved by more fully exploiting decision-theoretic methods and criteria that explicitly account for uncertain, possibly conflicting scientific beliefs and that can be fully studied by advocates and adversaries of a policy choice, in administrative decision-making involving risk assessment. The substitution of decision-theoretic frameworks for default assumption-driven policies also allows stakeholder attitudes toward risk to be incorporated into policy debates, so that the public and risk managers can more explicitly identify the roles of risk-aversion or other attitudes toward risk and uncertainty in policy recommendations. Decision theory provides a sound scientific way explicitly to account for new knowledge and its effects on eventual policy choices. Although these improvements can complicate regulatory analyses, simplifying default assumptions can create substantial costs to society and can prematurely cut off consideration of new scientific insights (e.g., possible beneficial health effects from exposure to sufficiently low 'hormetic' doses of some agents). In many cases, the administrative burden of applying decision-analytic methods is likely to be more than offset by improved effectiveness of regulations in achieving desired goals. Because many foreign jurisdictions adopt US EPA reasoning and methods of risk analysis, it may be especially valuable to incorporate decision-theoretic principles that transcend local differences among jurisdictions.