Long-Term Follow-Up of Patients after Acute Kidney Injury: Patterns of Renal Functional Recovery

Background and Objectives: Patients who survive acute kidney injury (AKI), especially those with partial renal recovery, present a higher long-term mortality risk. However, there is no consensus on the best time to assess renal function after an episode of acute kidney injury or agreement on the definition of renal recovery. In addition, only limited data regarding predictors of recovery are available. Design, Setting, Participants, & Measurements: From 1984 to 2009, 84 adult survivors of acute kidney injury were followed by the same nephrologist (RCRMA) for a median time of 4.1 years. Patients were seen at least once each year after discharge until end stage renal disease (ESRD) or death. In each consultation serum creatinine was measured and glomerular filtration rate estimated. Renal recovery was defined as a glomerular filtration rate value >= 60 mL/min/1.73 m2. A multiple logistic regression was performed to evaluate factors independently associated with renal recovery. Results: The median length of follow-up was 50 months (30-90 months). All patients had stabilized their glomerular filtration rates by 18 months and 83% of them stabilized earlier: up to 12 months. Renal recovery occurred in 16 patients (19%) at discharge and in 54 (64%) by 18 months. Six patients died and four patients progressed to ESRD during the follow up period. Age (OR 1.09, p < 0.0001) and serum creatinine at hospital discharge (OR 2.48, p = 0.007) were independent factors associated with non renal recovery. The acute kidney injury severity, evaluated by peak serum creatinine and need for dialysis, was not associated with non renal recovery. Conclusions: Renal recovery must be evaluated no earlier than one year after an acute kidney injury episode. Nephrology referral should be considered mainly for older patients and those with elevated serum creatinine at hospital discharge.

Protein Disulfide Isomerase Is Required for Platelet-derived Growth Factor-induced Vascular Smooth Muscle Cell Migration, Nox1 NADPH Oxidase Expression, and RhoGTPase Activation

Vascular Smooth Muscle Cell (VSMC) migration into vessel neointima is a therapeutic target for atherosclerosis and postinjury restenosis. Nox1 NADPH oxidase-derived oxidants synergize with growth factors to support VSMC migration. We previously described the interaction between NADPH oxidases and the endoplasmic reticulum redox chaperone protein disulfide isomerase (PDI) in many cell types. However, physiological implications, as well as mechanisms of such association, are yet unclear. We show here that platelet-derived growth factor (PDGF) promoted subcellular redistribution of PDI concomitant to Nox1-dependent reactive oxygen species production and that siRNA-mediated PDI silencing inhibited such reactive oxygen species production, while nearly totally suppressing the increase in Nox1 expression, with no change in Nox4. Furthermore, PDI silencing inhibited PDGF-induced VSMC migration assessed by distinct methods, whereas PDI overexpression increased spontaneous basal VSMC migration. To address possible mechanisms of PDI effects, we searched for PDI interactome by systems biology analysis of physical protein-protein interaction networks, which indicated convergence with small GTPases and their regulator RhoGDI. PDI silencing decreased PDGF-induced Rac1 and RhoA activities, without changing their expression. PDI co-immunoprecipitated with RhoGDI at base line, whereas such association was decreased after PDGF. Also, PDI co-immunoprecipitated with Rac1 and RhoA in a PDGF-independent way and displayed detectable spots of perinuclear co-localization with Rac1 and RhoGDI. Moreover, PDI silencing promoted strong cytoskeletal changes: disorganization of stress fibers, decreased number of focal adhesions, and reduced number of RhoGDI-containing vesicular recycling adhesion structures. Overall, these data suggest that PDI is required to support Nox1/redox and GTPase-dependent VSMC migration.

Combining accelerator and reactor measurements of theta(13): the first result

The lepton mixing angle theta(13), the only unknown angle in the standard three-flavor neutrino mixing scheme, is finally measured by the recent reactor and accelerator neutrino experiments. We perform a combined analysis of the data coming from T2K, MINOS, Double Chooz, Daya Bay and RENO experiments and find sin(2)2 theta(13) = 0.096 +/- 0.013(+/- 0.040) at 1 sigma (3 sigma) CL and that the hypothesis theta(13) = 0 is now rejected at a significance level of 7.7 sigma. We also discuss the near future expectation on the precision of the theta(13) determination by using expected data from these ongoing experiments.

Changes in spatial and temporal gene expression during incompatible interaction between common bean and anthracnose pathogen

Common bean, one of the most important legumes for human consumption, may have drastic reduction in yield due to anthracnose, a disease caused by the fungus Colletotrichum lindemuthianum. Rapid induction of the plant defense mechanisms is essential to establish an incompatible interaction with this pathogenic fungus. In this study, we evaluated spatial (leaves, epicotyls and hypocotyls) and temporal (24, 48, 72 and 96 hours after inoculation [HAI]) relative expression (RE) of 12 defense-related transcripts selected from previously developed ESTs libraries, during incompatible interaction between the resistant common bean genotype SEL 1308 and the avirulent anthracnose pathogen race 73, using real time quantitative RT-PCR (RT-qPCR) analysis. All selected transcripts, including the ones coding for pathogenesis-related (PR) proteins (PR1a, PR1b, PR2, and PR16a and PR16b) were differentially regulated upon pathogen inoculation. The expression levels of these transcripts were dependent on the tissue and time post inoculation. This study contributes to a better understanding of the kinetics of induced defenses against a fungal pathogen of common bean and may be used as a base line to study defenses against a broad range of pathogens including bacteria as well as non-host resistance. (C) 2012 Elsevier GmbH. All rights reserved.

Bulk neutrinos as an alternative cause of the gallium and reactor anti-neutrino anomalies

We consider an alternative explanation for the deficit of nu(e) in Ga solar neutrino calibration experiments and of the (nu) over bar (e) in short-baseline reactor experiments by a model where neutrinos can oscillate into sterile Kaluza-Klein modes that can propagate in compactified submicrometer flat extra dimensions. We have analyzed the results of the gallium radioactive source experiments and 19 reactor experiments with baseline shorter than 100 m, and showed that these data can be fit into this scenario. The values of the lightest neutrino mass and of the size of the largest extra dimension that are compatible with these experiments are mostly not excluded by other neutrino oscillation experiments.

Vocal and territorial behavior in the Smith frog (Hypsiboas faber): Relationships with plasma levels of corticosterone and testosterone

The possible trade-off between the roles of glucocorticoids as facilitators of energy substrate mobilization and neural inhibitors of sexual behavior during breeding season is under debate. We studied the relationship between calling and territorial behavior with plasma levels of corticosterone (CORT) and plasma levels of testosterone (T) across the breeding season of Hypsiboas faber, a large and territorial Neotropical treefrog. We investigated these relationships through focal observations of males calling naturally, followed by blood sampling for hormonal radioimmunoassay. We additionally used an experimental approach, which consisted of broadcasting recorded advertisement calls for 10 min to simulate an invasion in the territory of the focal subjects, followed by behavioral observation and blood sampling for hormonal radioimmunoassay. Results showed a pattern of co-variation between CORT and T across the breeding season. Furthermore, individual variation in CORT and T was related to different aspects of behavior: individuals with higher CORT showed higher calling rates, and individuals with higher steroid levels, mainly T, showed higher responsivity to social stimulation by other males in the chorus. Experimental simulation of territorial intrusion by using playback of advertisement calls of this species did not elicit consistent changes in agonistic behavior and CORT, but decreased T in focal males. (C) 2012 Elsevier Inc. All rights reserved.

Two-degree-of-freedom vortex-induced vibration of circular cylinders with very low aspect ratio and small mass ratio

The investigation of vortex-induced vibration on very short cylinders with two degrees of freedom has drawn the attention of a large number of researchers. Some investigations on such a problem are carried out in order to have a better understanding of the physics involved in vortex-induced motions of floating bodies such as offshore platforms. In this paper, experiments were carried out in a recirculating water channel over the range of Reynolds number 6000responses, visibly identified in the plots of nondimensional frequency, as well as by the trajectories in the XY-plane, Lissajous figures, particularly in the case of m⁎=1.00 and L/D=2.0, when 8-shape trajectories were clearly observed. The case of m⁎=1.00 deserves more attention because of its smaller amplitude compared to the cases with the same aspect ratio and a larger mass ratio. This counter-intuitive behavior seems to be related to the energy transferring process from the steady stream to the oscillatory hydroelastic system. Finally, it is noteworthy that the characteristic of the “Strouhal-like” number decreases when the aspect ratio decreases, as also observed in previous works available in the literature, most of them for stationary cylinders.

Two-degree-of-freedom vortex-induced vibration of circular cylinders with very low aspect ratio and small mass ratio

The investigation of vortex-induced vibration on very short cylinders with two degrees of freedom has drawn the attention of a large number of researchers. Some investigations on such a problem are carried out in order to have a better understanding of the physics involved in vortex-induced motions of floating bodies such as offshore platforms. In this paper, experiments were carried out in a recirculating water channel over the range of Reynolds number 6000responses, visibly identified in the plots of nondimensional frequency, as well as by the trajectories in the XY-plane, Lissajous figures, particularly in the case of m⁎=1.00 and L/D=2.0, when 8-shape trajectories were clearly observed. The case of m⁎=1.00 deserves more attention because of its smaller amplitude compared to the cases with the same aspect ratio and a larger mass ratio. This counter-intuitive behavior seems to be related to the energy transferring process from the steady stream to the oscillatory hydroelastic system. Finally, it is noteworthy that the characteristic of the “Strouhal-like” number decreases when the aspect ratio decreases, as also observed in previous works available in the literature, most of them for stationary cylinders.

Studio di catalisi termoattivate per compositi poliuretanici

One of the key processing parameters in thermoset composites manufacturing is to have an optimum balance between open time and cure time. Long open times followed with a fast cure profile (also referred as snap cure or “hockey stick” shaped profiles) are required on applications like Pultrusion, Filament Winding, Resin Transfer Molding (RTM) and Infusion. In this work, several factors affecting the reactivity of a base line polyurethane formulation were studied. The addition of different components such as internal mold release agents, cross-linker, polyols having different molecular structure and isocyanates having different functionality were studied. A literature search was conducted to identify the main catalyst packages existing in the market. The reactivity of catalyst based on tertiary amines, orgamometallic salts, and co-catalyst of amine-organometallic complexes was characterized. Addition of quelants agents such as thioglycerol and acetyl acetone to delay the catalyst activity were also considered. As a consequence of this work a vast reactivity map was generated. This should guide the formulation designer in future product generations for the further development of the mentioned applications. Recommendations on measurements systems and further areas of exploration are also given.

Generierung eines BAC-transgenen Mausstamms zur Analyse von Melanomen

Da Tumorerkrankungen ein enormes Gesundheitsproblem in der westlichen Welt darstellen, wird eine Vielzahl neuer Behandlungsstrategien entwickelt. Neuartige Tumor-Therapeutika werden jedoch üblicherweise zunächst an Tiermodellen evaluiert, bevor sie am Menschen angewandt werden.rnIn der vorliegenden Arbeit wurde ein BAC-transgenes Mausmodell generiert, welches als autochthones Melanommodell zur Anwendung kommen sollte.rnZunächst wurde dafür ein DNA-Konstrukt erzeugt. Dieses enthält die Melanom-Onkogene BrafV600E, Cdk4R24C und Mitf deren Expression durch die Tamoxifen-induzierbare Rekombinase CreERT2 kontrollierbar sein sollte. Die Verwendung des Tyrosinasepromoters sollte die melanozytenspezifische Expression der eingebrachten Gene gewährleisten. Ein weiterer Bestandteil des Konstrukts ist ein Luziferase-Gen, welches die Lokalisierung Onkogen-exprimierender Zellen durch in vivo-Biolumineszenz-Imaging erlaubt, da die Onkogen- und Luziferase-Expression durch 2A-Sequenzen gekoppelt sind.rnVor der Generierung der transgenen Tiere sollten in vitro Analysen die Funktionalität des Konstruktteils, bestehend aus den Onkogenen und der Luziferase, klären. Zu diesem Zweck wurde die Zelllinie C22 mit einem Expressionsvektor transfiziert, welcher den genannten Konstruktteil enthielt. Es konnte ein Anstieg der Braf- und Cdk4-Expression auf Protein Ebene, das Vorhandensein von Luziferase-Aktivität und die Aktivierung des MAP-Kinase-Signalwegs nachgewiesen werden. Die Funktionalität des untersuchten Konstruktteils war damit nahegelegt und die Generierung der transgenen Tiere wurde fortgesetzt.rnDie Pronukeus-Injektion resultierte schließlich in 3 Founder-Tieren, die mittels PCR und Southern Blot identifiziert wurden und die Bezeichnung „B6 tg Tyr iOnkogene“ (TyriOn) erhielten. Durch Verkreuzen der Founder-Tiere mit C57BL/6 Mäusen wurden im weiteren Verlauf 3 Linien erzeugt. Bei in vivo Biolumineszenz-Messungen zeigten Tiere der Linie D einen gewissen Grad an Hintergrund-Luziferase-Aktivität, die jedoch durch Tamoxifen-Injektionen verstärkt werden konnte. In den Folgegenerationen ging diese Tamoxifen-induzierte Verstärkung der Luziferase-Aktivität teilweise verloren. Es wurde die Vermutung angestellt, dass funktionelle und nicht-funktionelle Varianten des Transgens an unterschiedlichen Stellen im Genom von Founder D integriert hatten, und sich in den folgenden Generationen auf die Nachkommen verteilten. Die mangelnde Induzierbarkeit betroffener Tiere konnte nicht auf fehlende Integrität der Sequenz „iOnkogene“ in diesen Tieren oder auf nicht-funktionelle loxP-Stellen im Konstrukt zurückgeführt werden.rnTamoxifen-Injektionen führten in TyriOn-D Tieren im Laufe von 15 Monaten nicht zur Entwicklung von Tumoren. Ebenso wenig konnten in TyriOn-D / Cre del Tieren, welche die eingebrachten Onkogene maximal exprimieren sollten, Tumoren detektiert werden. Um zu analysieren, ob die eingebrachten Onkogene die Bildung von Tumoren begünstigen, wurden TyriOn-D Tiere mit dem Melanom-anfälligen Stamm MT/ret verkreuzt. Hierzu konnte im Rahmen dieser Arbeit noch kein Ergebnis erzielt werden. Allerdings konnte in Melanomen von TyriOn-D / MT/ret Tieren Luziferase-Aktivität bei in vivo Biolumineszenz-Messungen und CreERT2 RNA durch RT-PCR detektiert werden.rnTyriOn-D / MT/ret Tiere werden im weiteren Verlauf dieses Projektes nicht nur der Analyse der Melanomentwicklung dienen. Deren Tumore ermöglichen außerdem weitere Untersuchungen bezüglich der Funktionalität des Konstrukts, die teilweise in TyriOn Tieren keine Resultate ergaben.

Atopic dermatitis - from new pathophysiologic insights to individualized therapy

Recently, important novel insights into the complex pathophysiology of atopic dermatitis (AD) have been gained. However, in most cases the therapy of AD is limited to base line therapy with emollients combined with symptomatic, rather general immunosuppressive treatment approaches of the flare-ups. Latest research findings together with experiences from daily clinical practice, which support the concept that a combination of general disease features together with specific trigger factors in the individual patients drive the disease, might be helpful for a subclassification of patients with AD based on the most relevant pathophysiologic modifications. Subclassification of patients with AD seems indispensable to introduce rationale-based, individualized treatment approaches of AD, which target specific modified pathways. In this review, we provide an overview about a selection of pathophysiologic pathways, which hold promise to represent targets of such therapeutic approaches in the near future.

Hydrologic and Water Quality Assessment of Miller Run: A Study of Bucknell University’s Impact

Human development causes degradation of stream ecosystems due to impacts on channel morphology, hydrology, and water quality. Urbanization, the second leading cause of stream impairment, increases the amount of impervious surface cover, thus reducing infiltration and increasing surface runoff of precipitation, which ultimately affects stream hydrologic process and aquatic biodiversity. The main objective of this study was to assess the overall health of Miller Run, a small tributary of the Bull Run and Susquehanna River watersheds, through an integrative hydrologic and water quality approach in order to determine the degree of Bucknell University’s impact on the stream. Hydrologic conditions, including stage and discharge, and water quality conditions, including total suspended solids, ion, nutrient, and dissolved metal concentrations, specific conductivity, pH, and temperature, were measured and evaluated at two sampling sites (upstream and downstream of Bucknell’s main campus) during various rain events from September 2007 to March 2008. The primary focus of the stream analysis was based on one main rain event on 26 February 2008. The results provided evidence that Miller Run is impacted by Bucknell’s campus. From a hydrologic perspective, the stream’s hydrograph showed the exact opposite pattern of what would be expected from a ‘normal’ stream. Miller run had a flashier downstream hydrograph and a broader upstream hydrograph, which was more than likely due to the increased amount of impervious surface cover throughout the downstream half of the watershed. From a water quality perspective, sediment loads increased at a faster rate and were significantly higher downstream compared to upstream. These elevated sediment concentrations were probably the combined result of sediment runoff from upstream and downstream construction sites that were being developed over the course of the study. Sodium, chloride, and potassium concentrations, in addition to specific conductivity, also significantly increased downstream of Bucknell’s campus due to the runoff of road salts. Calcium and magnesium concentrations did not appear to be impacted by urbanization, although they did demonstrate a significant dilution effect downstream. The downstream site was not directly affected by elevated nitrate concentrations; however, soluble reactive phosphorus concentrations tended to increase downstream and ammonium concentrations significantly peaked partway through the rain event downstream. These patterns suggest that Miller Run may be impacted by nutrient runoff from the golf course, athletic fields, and/or fertilizers applications on the main campus. Dissolved manganese and iron concentrations also appeared to slightly increase downstream, demonstrating the affect of urban runoff from roads and parking lots. pH and temperature both decreased farther downstream, but neither showed a significant impact of urbanization. More studies are necessary to determine how Miller Run responds to changes in season, climate, precipitation intensity, and land-use. This study represents the base-line analysis of Miller Run’s current hydrologic and water quality conditions; based on these initial findings, Bucknell should strongly consider modifications to improve storm water management practices and to reduce the campus’s overall impact on the stream in order to enhance and preserve the integrity of its natural water resources.

Translocation and potential neurological effects of fine and ultrafine particles a critical update

ABSTRACT: Particulate air pollution has been associated with respiratory and cardiovascular disease. Evidence for cardiovascular and neurodegenerative effects of ambient particles was reviewed as part of a workshop. The purpose of this critical update is to summarize the evidence presented for the mechanisms involved in the translocation of particles from the lung to other organs and to highlight the potential of particles to cause neurodegenerative effects.Fine and ultrafine particles, after deposition on the surfactant film at the air-liquid interface, are displaced by surface forces exerted on them by surfactant film and may then interact with primary target cells upon this displacement. Ultrafine and fine particles can then penetrate through the different tissue compartments of the lungs and eventually reach the capillaries and circulating cells or constituents, e.g. erythrocytes. These particles are then translocated by the circulation to other organs including the liver, the spleen, the kidneys, the heart and the brain, where they may be deposited. It remains to be shown by which mechanisms ultrafine particles penetrate through pulmonary tissue and enter capillaries. In addition to translocation of ultrafine particles through the tissue, fine and coarse particles may be phagocytized by macrophages and dendritic cells which may carry the particles to lymph nodes in the lung or to those closely associated with the lungs. There is the potential for neurodegenerative consequence of particle entry to the brain. Histological evidence of neurodegeneration has been reported in both canine and human brains exposed to high ambient PM levels, suggesting the potential for neurotoxic consequences of PM-CNS entry. PM mediated damage may be caused by the oxidative stress pathway. Thus, oxidative stress due to nutrition, age, genetics among others may increase the susceptibility for neurodegenerative diseases. The relationship between PM exposure and CNS degeneration can also be detected under controlled experimental conditions. Transgenic mice (Apo E -/-), known to have high base line levels of oxidative stress, were exposed by inhalation to well characterized, concentrated ambient air pollution. Morphometric analysis of the CNS indicated unequivocally that the brain is a critical target for PM exposure and implicated oxidative stress as a predisposing factor that links PM exposure and susceptibility to neurodegeneration.Together, these data present evidence for potential translocation of ambient particles on organs distant from the lung and the neurodegenerative consequences of exposure to air pollutants.

The PRO-AGE study: an international randomised controlled study of health risk appraisal for older persons based in general practice

BACKGROUND: This paper describes the study protocol, the recruitment, and base-line data for evaluating the success of randomisation of the PRO-AGE (PRevention in Older people-Assessment in GEneralists' practices) project. METHODS/DESIGN: A group of general practitioners (GPs) in London (U.K.), Hamburg (Germany) and Solothurn (Switzerland) were trained in risk identification, health promotion, and prevention in older people. Their non-disabled older patients were invited to participate in a randomised controlled study. Participants allocated to the intervention group were offered the Health Risk Appraisal for Older Persons (HRA-O) instrument with a site-specific method for reinforcement (London: physician reminders in electronic medical record; Hamburg: one group session or two preventive home visits; Solothurn: six-monthly preventive home visits over a two-year period). Participants allocated to the control group received usual care. At each site, an additional group of GPs did not receive the training, and their eligible patients were invited to participate in a concurrent comparison group. Primary outcomes are self-reported health behaviour and preventative care use at one-year follow-up. In Solothurn, an additional follow-up was conducted at two years. The number of older persons agreeing to participate (% of eligible persons) in the randomised controlled study was 2503 (66.0%) in London, 2580 (53.6%) in Hamburg, and 2284 (67.5%) in Solothurn. Base-line findings confirm that randomisation of participants was successful, with comparable characteristics between intervention and control groups. The number of persons (% of eligible) enrolled in the concurrent comparison group was 636 (48.8%) in London, 746 (35.7%) in Hamburg, and 1171 (63.0%) in Solothurn. DISCUSSION: PRO-AGE is the first large-scale randomised controlled trial of health risk appraisal for older people in Europe. Its results will inform about the effects of implementing HRA-O with different methods of reinforcement.

[Fixed-combination of losartan/hydrochlorothiazide 100 mg/25 mg. Tolerability and efficacy on blood pressure measured in the practice and for 24 hours]

BACKGROUND: A high proportion of patients with essential hypertension need a combination therapy to reach the therapeutic goal. In the present study, the tolerability and efficacy of a fixed, once daily combination of the AT1 blocker Losartan (100 mg) and the diuretic hydrochlorothiazide (HCTZ) (25 mg) for patients in the real-life situation was investigated. Special consideration was given to the results of ambulatory 24-hourblood pressure (ABP) measurements. METHODS: The open label, prospective non-interventional surveillance study took place from October 2005 to June 2006. A total of 1139 patients over 18 years in age were included whose blood pressures could not be adequately treated with HCTZ alone and for whom an individual dose titration for Losartan and HCTZ had already been performed. RESULTS: The average age (+/- standard deviation) of the patients was 61.2 +/- 11.6 years; 55.8% were men. Comorbidities were common. Specifically, left ventricular hypertrophy was present in 3.1% of the patients, coronary heart disease in 30.1%, chronic heart failure in 11.8% and status post myocardial infarction in 10.5%, respectively. In addition to the Losartan/HCTZ treatment, 61.0% of the patients received a second antihypertensive medicine. After an average treatment duration of 50.4 +/- 17.2 days, the base line systolic blood pressure of 160.8 +/- 16.3 mmHg decreased by 24.0 +/- 17.0 mmHg (-14.4%) and the diastolic blood pressure of 94.4 +/- 9.9 mmHg decreased by 11.8 +/- 10.2 mmHg (-11.8%). For the ABP measurements, the overall average systolic and diastolic blood pressures fell by 16.9 +/- 14.2 mmHg and 8.8 +/-10.3 mmHg, the day average by 17.3 +/- 14.8 mmHg and 9.0 +/- 10.2 mmHg and the night average by 15.1 +/- 17.6 mmHg and 7.8 +/- 11.7 mmHg, respectively. In twelve of the 1139 patients (1.1%), a total of 15 adverse events occurred. A causal connection with the medication was suspected in only in one case (one patient with three). CONCLUSION: The combination of Losartan/HCTZ 100/25 mg, as the exclusive therapy or in addition to other antihypertensive medicines, was for patients, many of whom who had comorbidities, in the real-life situation well tolerated and effective. The efficacy was demonstrated also during the night through ABP.