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Elevated blood ketone levels (ketosis) in inpatients with diabetes can herald diabetic ketoacidosis (DKA). However, ketosis can also occur in individuals without diabetes in certain settings. It is unclear what proportion of inpatients with ketosis are in DKA and which patients are at the highest risk of DKA. This study determined that many ketone tests are performed in individuals at low risk of DKA, and a β‐hydroxybutyrate <1.0 mmol/L had a low incidence of DKA and less need for escalation in their management. [ABSTRACT FROM AUTHOR]

As interest mounts in nature‐based solutions (NBS) for flood mitigation as complementary options to civil‐engineering measures, possible flood‐protection strategies have become more diverse and hence complicated to assess. We offer a straightforward and educational protocol targeted for effectiveness analysis and decision making involving stakeholder participation. It is based on the concept of flood‐excess volume (FEV), the volume exceeding a threshold and generating flood damage, and explores what fraction of FEV is reduced, and at what cost, by particular flood‐mitigation measures. Quantification and interpretation of cost scenarios are facilitated using a graphical display that is easy to understand and encapsulates concepts of flood magnitude, FEV and protection‐measures efficacy. It is exemplified for two recent extreme‐flood events on the River Calder in Mytholmroyd (Yorkshire, United Kingdom) and the River Brague in Biot (Alpes‐Maritimes, France). Each case has different flood‐mitigation measures such as natural water‐retention measures, tree planting, river‐bed widening, or use of reservoirs and floods walls. Our straightforward protocol enables fast, quantifiable and easy‐to‐understand exploration of protection strategies using multiple measures, and in doing so highlights the issue of NBS scalability. [ABSTRACT FROM AUTHOR]

Abstract: Interactions of amyloid‐β (Aβ) peptides and cellular membranes are proposed to be closely related with Aβ neurotoxicity in Alzheimer's disease. In this study, we systematically investigated the effect of the N‐terminal hydrophilic region of Aβ40 on its amyloidogenesis and interaction with supported phospholipid bilayer. Our results show that modulation of the charge properties of the dynamic N‐terminal region dramatically influences the aggregation properties of Aβ. Furthermore, our results demonstrate that the N‐terminal charged residues play a crucial role in driving the early adsorption and latter remobilization of the peptide on membrane bilayer, and mediating the rigidity and viscoelasticity properties of the bound Aβ40 at the membrane interface. The results provide new mechanistic insight into the early Aβ‐membrane interactions and binding, which may be critical for elucidating membrane‐mediated Aβ amyloidogenesis in a physiological environment and unravelling the origin of Aβ neurotoxicity. [ABSTRACT FROM AUTHOR]

Abstract: Elucidating local dynamics of protein aggregation is crucial for understanding the mechanistic details of protein amyloidogenesis. Herein, we studied the residue‐specific dynamics and local environmental changes of Aβ40 along the course of aggregation by using para‐cyanophenylalanine (PheCN) as a fluorescent and vibrational probe. Our results show that the PheCN residues introduced at various positions all exhibited an immediate decay of fluorescence intensity, indicating a relatively synergistic process in early oligomer formation. The fast decreases in the fluorescence intensities of residues 19 and 20 in the central hydrophobic core region and residue 10 in the N‐terminal region suggest that they play crucial roles in the formation of the oligomeric core. The PheCN4 residue exhibits a remarkably slower decrease in fluorescence intensity, implicating its dynamic conformational characteristics in oligomer and fibril formation. Our results also suggest that the N‐terminal residues in fibrils are surrounded by a relatively hydrophobic local environment, as opposed to being solvated. [ABSTRACT FROM AUTHOR]

Objective: Disability or death occurs more frequently in patients with hemorrhagic transformation (HT) after ischemic stroke. In rat models of stroke, sulfonylurea (SU) drugs such as glibenclamide (adopted US name, glyburide) confer protection against swelling and HT through actions on the novel SUR1-regulated NCCa-ATP channel. Here, we sought to determine whether the use of SU drugs in patients with diabetes mellitus (DM) presenting with acute ischemic stroke might influence the incidence of HT. Methods: We retrospectively analyzed data on 220 patients with DM who presented with acute ischemic stroke, 43 of whom were managed with and continued to receive SU drugs, and 177 of whom were managed without (controls). Results: During a median length of stay in hospital of 11 days, 20 control patients (11%) experienced symptomatic HT (sHT), whereas no patient in the SU group experienced sHT ( p = 0.016). No patient in the SU group died, compared to 18 (10%) in the control group ( p = 0.027). Similarly favorable outcomes were observed after matching for baseline imbalances and excluding outliers. In support of the proposed mechanism, we present a case of sHT in which an analysis of brain tissues obtained intraoperatively showed prominent upregulation of SUR1, the target of SU drugs, in microvessels and neurons. Interpretation: We conclude that, in diabetic patients with acute ischemic stroke, prior and continued use of SU drugs is associated with reduced sHT compared to those whose treatment regimen does not include SU drugs. ANN NEUROL 2012;72:799-806 [ABSTRACT FROM AUTHOR]

The current study examined the frequency and correlates of coercive sexual behaviors by male Iraq, Afghanistan, and/or Vietnam veterans recruited from a Veterans Affairs trauma recovery clinic (n = 92) toward their female partners. Men who reported sexual aggression in the past year (n = 37) compared to men who did not report sexual aggression in the past year (n = 55) more frequently reported impulsive aggression, dominating/isolating, and physically assaulting their partner, and were more likely to have a substance abuse diagnosis. Sexually aggressive men were significantly less likely than nonsexually aggressive men to have a diagnosis of depression. Posttraumatic stress disorder, an established risk factor for nonsexual partner aggression among veterans, was not associated with sexual aggression. [ABSTRACT FROM AUTHOR]

Our long term interest is to develop a developmental model of impulsive aggression based on a confluence of social, psychological and biological features. This approach incorporates neurobiological research, which has identified language processing deficits as a unique characteristic of impulsive aggressors and extends it to include emotional deficits. As an initial test of this hypothesis, we examined whether empathy and alexithymia were associated with impulsive aggression. Regressions were performed to explore the associations among impaired empathy, alexithymia, impulsive aggression, verbal and physical general aggression. Among impulsive aggressive veterans (n = 38) recruited from a VA trauma clinic, alexithymia predicted impulsive aggression and empathic deficits predicted verbal aggression. Neither emotional awareness deficit predicted general physical aggression in this middle-aged sample. Results suggested that empathic deficits were associated with general verbal aggression, but alexithymia was uniquely associated with impulsive aggression. Consideration of alexithymia in impulsive aggression has implications for its etiology, prevention and treatment. Published in 2008 by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abnormalities of cerebral blood flow during and following hypoxia and ischemia contribute to the progression of tissue injury. Oxidative stress during and following hypoxia is known to markedly increase superoxide anion concentration. There is conflicting evidence that the concentration of superoxide anion regulates cerebral blood flow through its effect on vascular tone, although difficulties in measurement of superoxide anion complicate these studies. In order to test the hypothesis that changes in cerebral blood flow during and following hypoxia are due to changes in extracellular superoxide anion levels, we examined tissue oxygen levels by fiberoptic oximetry and superoxide anion levels using a previously validated cytochrome c coated electrode on the cortical surface and correlated these measurements to cerebral blood flow measured by laser Doppler in rats subjected to 20 min of hypoxia followed by hyperoxic reoxygenation recovery. The results showed a burst of superoxide anion with the onset of reoxygenation that temporally correlated with a transient peak in tissue oxygen tension lasting 10 min. and was eliminated by pretreatment with Cu–Zn superoxide dismutase conjugated to polyethylene glycol. Cerebral blood flow did not differ during hypoxia or recovery in the polyethylene glycol conjugated superoxide dismutase and control treatment groups. This study demonstrated no effect of increased superoxide anion concentration on cerebral blood flow during hyperoxic recovery following hypoxia. [Copyright &y& Elsevier]