Prehypertensive blood pressures and regional cerebral blood flow independently relate to cognitive performance in midlife

Background High blood pressure is thought to contribute to dementia in late life, but our understanding of the relationship between individual differences in blood pressure ( BP ) and cognitive functioning is incomplete. In this study, cognitive performance in nonhypertensive midlife adults was examined as a function of resting BP and regional cerebral blood flow ( rCBF ) responses during cognitive testing. We hypothesized that BP would be negatively related to cognitive performance and that cognitive performance would also be related to rCBF responses within areas related to BP control. We explored whether deficits related to systolic BP might be explained by rCBF responses to mental challenge. Methods and Results Healthy midlife participants (n=227) received neuropsychological testing and performed cognitive tasks in a magnetic resonance imaging scanner. A pseudocontinuous arterial spin labeling sequence assessed rCBF in brain areas related to BP in prior studies. Systolic BP was negatively related to 4 of 5 neuropsychological factors (standardized β&gt;0.13): memory, working memory, executive function, and mental efficiency. The rCBF in 2 brain regions of interest was similarly related to memory, executive function, and working memory (standardized β&gt;0.17); however, rCBF responses did not explain the relationship between resting systolic BP and cognitive performance. Conclusions Relationships at midlife between prehypertensive levels of systolic BP and both cognitive and brain function were modest but suggested the possible value of midlife intervention. </jats:sec

Psychology and BAPCPA: Enhanced Disclosure and Emotion

This article describes a program of research that applies social analytic jurisprudence to test some of the assumptions in consumer bankruptcy law and policy.4 Our work first seeks to describe selected provisions from the newly enacted bankruptcy amendments that pertain to enhanced disclosure requirements, and then to locate some of the behavioral assumptions implicit in these provisions. 5 Next, we assess the accuracy of these assumptions based on an experiment that we conducted looking at a simulated online shopping trip that we constructed specifically to test the effects of enhanced disclosur

One transition, many transitions? A corpus-based study of societal sustainability transition discourses in four civil society’s proposals

When the civil society makes ‘transition’ its label, it cannot be assumed that different civil society actors share compatible varieties of localist or radical transformationists discourses. This study has comparatively analyzed the discourses in four civil society sustainability transition proposals using a corpus-based methodology. We found that the proposals are similar as they identify the economy as an object and an entry point for transition, frame the economy as embedded in the socio–ecological system, ascribe agency to grassroots movements for transitions from the bottom–up. We also found crucial differences among the discourses regarding the role of the State, the degree of reform or radical innovation, the degree of imaginative character of the sustainability vision, the degree of opposition to capitalism. We suggest that insights on how the civil society employs notions of transition with respect to the themes of politics, emotions and place can help advance theorizations and practices of societal sustainability transitions led by the civil society

Evaluation of the accuracy of serum MMP-9 as a test for colorectal cancer in a primary care population

Background Bowel cancer is common and is a major cause of death. Meta-analysis of randomised controlled trials estimates that screening for colorectal cancer using faecal occult blood (FOB) test reduces mortality from colorectal cancer by 16%. However, FOB testing has a low positive predictive value, with associated unnecessary cost, risk and anxiety from subsequent investigation, and is unacceptable to a proportion of the target population. Increased levels of an enzyme called matrix metalloproteinase 9 (MMP-9) have been found to be associated with colorectal cancer, and this can be measured from a blood sample. Serum MMP-9 is potentially an accurate, low risk and cost-effective population screening tool. This study aims to evaluate the accuracy of serum MMP-9 as a test for colorectal cancer in a primary care population. Methods/Design People aged 50 to 69 years, who registered in participating general practices in the West Midlands Region, will be asked to complete a questionnaire that asks about symptoms. Respondents who describe any colorectal symptoms (except only abdominal bloating and/or anal symptoms) and are prepared to provide a blood sample for MMP9 estimation and undergo a colonoscopy (current gold standard investigation) will be recruited at GP based clinics by a research nurse. Those unfit for colonoscopy will be excluded. Colonoscopies will be undertaken in dedicated research clinics. The accuracy of MMP-9 will be assessed by comparing the MMP-9 level with the colonoscopy findings, and the combination of factors (e.g. symptoms and MMP-9 level) that best predict a diagnosis of malignancy (invasive disease or polyps) will be determined. Discussion Colorectal cancer is a major cause of morbidity and mortality. Most colorectal cancers arise from adenomas and there is a period for early detection by screening, but available tests have risks, are unacceptable to many, have high false positive rates or are expensive. This study will establish the potential of serum MMP-9 as a screening test for colorectal cancer. If it is confirmed as accurate and acceptable, this serum marker has the potential to assist with reducing the morbidity and mortality from colorectal cancer

Combination therapy for severe portopulmonary hypertension in a child allows for liver transplantation

Severe PPHTN is a contraindication to liver transplantation and predicts an abysmal 5‐year outcome. It is defined as a resting mPAP >45 mm Hg with a mean pulmonary artery wedge pressure of 3 wood units in the setting of portal hypertension. There have been limited reports of successful treatment of PPHTN leading to successful liver transplantation in adults, and one reported use of monotherapy as a bridge to successful liver transplant in pediatrics. To our knowledge, we describe the first use of combination therapy as a successful bridge to liver transplantation in a pediatric patient with severe PPHTN. This report adds to the paucity of data in pediatrics on the use of pulmonary vasodilator therapy in patients with severe PPHTN as a bridge to successful liver transplantation. Early diagnosis in order to mitigate or avoid the development of irreversible pulmonary vasculopathy that would preclude candidacy for liver transplantation is crucial, but our report demonstrates that combination therapy can be administered safely, quickly, and may allow for successful liver transplantation in patients with severe PPHTN

Reactive oxygen species induce virus-independent MAVS-oligomerization in systemic lupus erythematosus

The increased expression of genes induced by type I interferon (IFN) is characteristic of viral infections and systemic lupus erythematosus (SLE). We showed that mitochondrial antiviral signaling (MAVS) protein, which normally forms a complex with retinoic acid gene I (RIG-I)–like helicases during viral infection, was activated by oxidative stress independently of RIG-I helicases. We found that chemically generated oxidative stress stimulated the formation of MAVS oligomers, which led to mitochondrial hyperpolarization and decreased adenosine triphosphate production and spare respiratory capacity, responses that were not observed in similarly treated cells lacking MAVS. Peripheral blood lymphocytes of SLE patients also showed spontaneous MAVS oligomerization that correlated with the increased secretion of type I IFN and mitochondrial oxidative stress. Furthermore, inhibition of mitochondrial reactive oxygen species (ROS) by the mitochondria-targeted antioxidant MitoQ prevented MAVS oligomerization and type I IFN production. ROS-dependent MAVS oligomerization and type I IFN production were reduced in cells expressing the MAVS-C79F variant, which occurs in 30% of sub-Saharan Africans and is linked with reduced type I IFN secretion and milder disease in SLE patients. Patients expressing the MAVS-C79F variant also had reduced amounts of oligomerized MAVS in their plasma compared to healthy controls. Together, our findings suggest that oxidative stress–induced MAVS oligomerization in SLE patients may contribute to the type I IFN signature that is characteristic of this syndrome

Home Parenteral Nutrition: A Hospital‐Based Program with Commercial Logistic Support

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141442/1/jpen0585.pd

A Cross-Linguistic Pressure for Uniform Information Density in Word Order

While natural languages differ widely in both canonical word order and word order flexibility, their word orders still follow shared cross-linguistic statistical patterns, often attributed to functional pressures. In the effort to identify these pressures, prior work has compared real and counterfactual word orders. Yet one functional pressure has been overlooked in such investigations: the uniform information density (UID) hypothesis, which holds that information should be spread evenly throughout an utterance. Here, we ask whether a pressure for UID may have influenced word order patterns cross-linguistically. To this end, we use computational models to test whether real orders lead to greater information uniformity than counterfactual orders. In our empirical study of 10 typologically diverse languages, we find that: (i) among SVO languages, real word orders consistently have greater uniformity than reverse word orders, and (ii) only linguistically implausible counterfactual orders consistently exceed the uniformity of real orders. These findings are compatible with a pressure for information uniformity in the development and usage of natural languages

HK-2: An immortalized proximal tubule epithelial cell line from normal adult human kidney

HK-2: An immortalized proximal tubule epithelial cell line from normal adult human kidney. Studies assessing mechanisms of proximal tubular cell (PTC) physiology and pathophysiology increasingly utilize cell culture systems to avoid the complexity of whole organ/whole animal experiments. However, no well-differentiated PTC line derived from adult human kidney currently exists. Therefore, the goal of this research was to establish such a line by transduction with human papilloma virus (HPV 16) E6/E7 genes. A primary PTC culture from normal adult human renal cortex was exposed to a recombinant retrovirus containing the HPV 16 E6/E7 genes, resulting in a cell line designated HK-2 (human kidney-2) which has grown continuously in serum free media for more than one year. HK-2 cell growth is epidermal growth factor dependent and the cells retain a phenotype indicative of well-differentiated PTCs (positive for alkaline phosphatase, gamma glutamyltranspeptidase, leucine aminopeptidase, acid phosphatase, cytokeratin, α3β1 integrin, fibronectin; negative for factor VHI-related antigen, 6.19 antigen and CALLA endopeptidase). Furthermore, HK-2 cells retain functional characteristics of proximal tubular epithelium (Na+ dependent/phlorizin sensitive sugar transport; adenylate cyclase responsiveness to parathyroid, but not to antidiuretic, hormone). The E6/E7 genes are present in the HK-2 genome, as determined by PCR. To assess its potential usefulness as a tool for studying injury and repair, HK-2 cells were exposed to a toxic concentration of H2O2 ± iron chelation (deferoxamine) or hydroxyl radical scavenger (Na benzoate) therapy. Only the former blocked H2O2 cytotoxicity, reproducing results previously obtained with freshly isolated rat proximal tubular segments. In conclusion, an immortalized adult human PTC line has been established by transduction with HPV 16 E6/E7 genes. It appears to be well-differentiated on the basis of its histochemical, immune cytochemical, and functional characteristics, and it can reproduce experimental results obtained with freshly isolated PTCs. Thus, this new PTC line could have substantial research application