The detection and quantification of cyanobacterial toxins in water using the brine shrimp (Artemia salina) assay

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Nitrosamine exposure exacerbates high fat diet-mediated type 2 diabetes mellitus, non-alcoholic steatohepatitis, and neurodegeneration with cognitive impairment

BACKGROUND: The current epidemics of type 2 diabetes mellitus (T2DM), non-alcoholic steatohepatitis (NASH), and Alzheimer's disease (AD) all represent insulin-resistance diseases. Previous studies linked insulin resistance diseases to high fat diets or exposure to streptozotocin, a nitrosamine-related compound that causes T2DM, NASH, and AD-type neurodegeneration. We hypothesize that low-level exposure to nitrosamines that are widely present in processed foods, amplifies the deleterious effects of high fat intake in promoting T2DM, NASH, and neurodegeneration. METHODS: Long Evans rat pups were treated with N-nitrosodiethylamine (NDEA) by i.p. Injection, and upon weaning, they were fed with high fat (60%; HFD) or low fat (5%; LFD) chow for 6 weeks. Rats were evaluated for cognitive impairment, insulin resistance, and neurodegeneration using behavioral, biochemical, molecular, and histological methods. RESULTS: NDEA and HFD +/- NDEA caused T2DM, NASH, deficits in spatial learning, and neurodegeneration with hepatic and brain insulin and/or IGF resistance, and reductions in tau and choline acetyltransferase levels in the temporal lobe. In addition, pro-ceramide genes, which promote insulin resistance, were increased in livers and brains of rats exposed to NDEA, HFD, or both. In nearly all assays, the adverse effects of HFD+NDEA were worse than either treatment alone. CONCLUSIONS: Environmental and food contaminant exposures to low, sub-mutagenic levels of nitrosamines, together with chronic HFD feeding, function synergistically to promote major insulin resistance diseases including T2DM, NASH, and AD-type neurodegeneration. Steps to minimize human exposure to nitrosamines and consumption of high-fat content foods are needed to quell these costly and devastating epidemics

Aspartyl-(asparaginyl) β-Hydroxylase, Hypoxia-Inducible Factor-1α and Notch Cross-Talk in Regulating Neuronal Motility

Aspartyl-(Asparaginyl)-β-Hydroxylase (AAH ) promotes cell motility by hydroxylating Notch. Insulin and insulin-like growth factor, type 1 (IGF-I) stimulate AAH through Erk MAP K and phosphoinositol-3-kinase-Akt (PI3K-Akt). However, hypoxia/oxidative stress may also regulate AAH . Hypoxia-inducible factor-1alpha (HIF-1α) regulates cell migration, signals through Notch, and is regulated by hypoxia/oxidative stress, insulin/IGF signaling and factor inhibiting HIF-1α (FIH) hydroxylation. To examine cross-talk between HIF-1α and AAH , we measured AAH , Notch-1, Jagged-1, FIH, HIF-1α, HIF-1β and the hairy and enhancer of split 1 (HE S-1) transcription factor expression and directional motility in primitive neuroectodermal tumor 2 (PNET2) human neuronal cells that were exposed to H2O2 or transfected with short interfering RNA duplexes (siRNA) targeting AAH , Notch-1 or HIF-1α. We found that: (1) AAH , HIF-1α and neuronal migration were stimulated by H2O2; (2) si-HIF-1α reduced AAH expression and cell motility; (3) si-AAH inhibited Notch and cell migration, but not HIF-1α and (4) si-Notch-1 increased FIH and inhibited HIF-1α. These findings suggest that AAH and HIF-1α crosstalk within a hydroxylation-regulated signaling pathway that may be transiently driven by oxidative stress and chronically regulated by insulin/IGF signaling

Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance

The finding of more severe steatohepatitis in alcohol fed Long Evans (LE) compared with Sprague Dawley (SD) and Fisher 344 (FS) rats prompted us to determine whether host factors related to alcohol metabolism, inflammation, and insulin/IGF signaling predict proneness to alcohol-mediated liver injury. Adult FS, SD, and LE rats were fed liquid diets containing 0% or 37% (calories) ethanol for 8 weeks. Among controls, LE rats had significantly higher ALT and reduced GAPDH relative to SD and FS rats. Among ethanol-fed rats, despite similar blood alcohol levels, LE rats had more pronounced steatohepatitis and fibrosis, higher levels of ALT, DNA damage, pro-inflammatory cytokines, ADH, ALDH, catalase, GFAP, desmin, and collagen expression, and reduced insulin receptor binding relative to FS rats. Ethanol-exposed SD rats had intermediate degrees of steatohepatitis, increased ALT, ADH and profibrogenesis gene expression, and suppressed insulin receptor binding and GAPDH expression, while pro-inflammatory cytokines were similarly increased as in LE rats. Ethanol feeding in FS rats only reduced IL-6, ALDH1–3, CYP2E1, and GAPDH expression in liver. In conclusion, susceptibility to chronic steatohepatitis may be driven by factors related to efficiency of ethanol metabolism and degree to which ethanol exposure causes hepatic insulin resistance and cytokine activation

Examining the Connections within the Startup Ecosystem: A Case Study of St. Louis

This paper documents the resurgence of entrepreneurial activity in St. Louis by reporting on the collaboration and local learning within the startup community. This activity is happening both between entrepreneurs and between organizations that provide support, such as mentoring and funding, to entrepreneurs. As these connections deepen, the strength of the entrepreneurial ecosystem grows. Another finding from the research is that activity-based events, where entrepreneurs have the chance to use and practice the skills needed to grow their businesses, are most useful. St. Louis provides a multitude of these activities, such as Startup Weekend, 1 Million Cups, Code Until Dawn, StartLouis, and GlobalHack. Some of these are St. Louis specific, but others have nationwide or global operations, providing important implications for other cities

Exercise, cognition and Alzheimer’s disease: More is not necessarily better

Regional hypoperfusion, associated with a reduction in cerebral metabolism, is a hallmark of Alzheimer’s disease (AD) and contributes to cognitive decline. Cerebral perfusion and hence cognition can be enhanced by exercise. The present review describes first how the effects of exercise on cerebral perfusion in AD are mediated by nitric oxide (NO) and tissue-type plasminogen activator, the release of which is regulated by NO. A conclusion of clinical relevance is that exercise may not be beneficial for the cognitive functioning of all people with dementia if cardiovascular risk factors are present. The extent to which cardiovascular risk factors play a role in the selection of older people with dementia in clinical studies will be addressed in the second part of the review in which the effects of exercise on cognition are presented. Only eight relevant studies were found in the literature, emphasizing the paucity of studies in this field. Positive effects of exercise on cognition were reported in seven studies, including two that excluded and two that included patients with cardiovascular risk factors. These findings suggest that cardiovascular risk factors do not necessarily undo the beneficial effects of exercise on cognition in cognitively impaired people. Further research is called for, in view of the limitations of the clinical studies reviewed here.

High burden and frailty: association with poor cognitive performance in older caregivers living in rural areas

Introduction: Older caregivers living in rural areas may be exposed to three vulnerable conditions, i.e., those related to care, their own aging, and their residence context. Objective: To analyze the association of burden and frailty with cognition performance in older caregivers in rural communities. Method: In this cross-sectional survey, 85 older caregivers who cared for dependent elders were included in this study. Global cognition (Addenbrooke's Cognitive Examination – Revised; Mini Mental State Examination), burden (Zarit Burden Interview) and frailty (Fried's frailty phenotype) were assessed. All ethical principles were observed. Results: Older caregivers were mostly women (76.7%); mean age was 69 years. Cognitive impairment was present in 15.3%, severe burden in 8.2%, frailty in 9.4%, and pre-frailty in 52.9% of the older caregivers. More severely burdened or frail caregivers had worse cognitive performance than those who were not, respectively (ANOVA test). Caregivers presenting a high burden level and some frailty degree (pre-frail or frail) simultaneously were more likely to have a reduced global cognition performance. Conclusion: A significant number of older caregivers had low cognitive performance. Actions and resources to decrease burden and physical frailty may provide better cognition and well-being, leading to an improved quality of life and quality of the care provided by the caregivers

Patterns and predictors of place of cancer death for the oldest old

BACKGROUND: Cancer patients increasingly are among older age groups, but to date little work has examined the trends in cancer among older people, particularly in relation to end of life care and death. This study describes the older population who die of cancer and the factors which may affect their place of death. METHODS: A Cross-sectional analysis of national data was performed. The study included all people aged 75 and over dying of cancer in England and Wales between 1995 and 1999. The population was divided into exclusive 5 year age cohorts, up to 100 years and over. Descriptive analysis explored demographic characteristics, cancer type and place of death. RESULTS: Between 1995 and 1999, 315,462 people aged 75 and over were registered as dying from cancer. The number who died increased each year slightly over the 5 year period (1.2%). In the 75–79 age group, 55 % were men, in those aged 100 and over this fell to 16%. On reaching their hundreds, the most common cause of death for men was malignancies of the genital organs; and for women it was breast cancer. The most frequent place of death for women in their hundreds was the care home; for men it was hospitals. Those dying from lymphatic and haematopoietic malignancies were most likely to die in hospitals, those with head and neck malignancies in hospices and breast cancer patients in a care home. CONCLUSION: The finding of rising proportions of cancer deaths in institutions with increasing age suggests a need to ensure that appropriate high quality care is available to this growing section of the population

In Their Own Words: Assessment of Satisfaction with Residential Location among Migrants in Nairobi Slums

Using qualitative data collected from a sample of rural-urban migrants over the age of 15 in two Nairobi slums interviewed in 2008, this paper discusses the migrants’ extent of satisfaction with their residential location and decision to migrate. The study sheds light on why people continue to migrate to, and stay in, the rapidly growing slum settlements despite the high levels of poverty and poor health conditions in these areas. Tenure status is related to satisfaction for all ages. Environmental factors were frequently mentioned as a source of dissatisfaction. Life cycle and ‘age-cohort effects’ may also affect satisfaction for different age groups in terms of who is satisfied as well as the issues that are considered for satisfaction. High levels of dissatisfaction with slum life may be responsible for high out-migration in slum areas, although it does not mean that those who remain do so because they are satisfied. At the same time, challenges associated with slum life do not automatically signify dissatisfaction. Perceived success, as well as conditions in the area of origin can be used to explain and understand satisfaction/dissatisfaction with slum life. Satisfaction with migration and residential location may be related not only to the destination place, but also to events in the area of origin