The electrophysiology of glomerular mesangial cells

Glomerular mesangial cells (MC) are renal vascular cells that regulate the surface area of glomerular capillaries and thus, partly control glomerular filtration rate. Clarification of the signal transduction pathways and ionic mechanisms modulating MC tone are critical to understanding the physiology and pathophysiology of these cells, and the integrative role these cells play in fluid and electrolyte homeostasis. The patch clamp technique and an assay of cell concentration were used to electrophysiologically and pharmacologically analyze the ion channels of the plasmalemmal of human glomerular MC maintained in tissue culture. Moreover, the signal transduction pathways modulating channels involved in relaxation were investigated. Three distinct K$\sp+$-selective channels were identified: two low conductance channels (9 and 65pS) maintained MC at rest, while a larger conductance (206pS) K$\sp+$ channel was quiescent at rest. This latter channel was pharmacologically and biophysically similar to the large, Ca$\sp{2+}$-activated K$\sp+$ channel (BK$\rm\sb{Ca}$) identified in smooth muscle. BK$\rm\sb{Ca}$ played an essential role in relaxation of MC. In cell-attached patches, the open probability (P$\rm\sb{o}$) of BK$\rm\sb{Ca}$ increased from a basal level of $<$0.05 to 0.22 in response to AII (100nM)-induced mobilization of cytosolic Ca$\sp{2+}$. Activation in response to contractile signals (membrane depolarization and Ca$\sp{2+}$ mobilization) suggests that BK$\rm\sb{Ca}$ acts as a low gain feedback regulator of contraction. Atrial natriuretic factor (ANF; 1.0$\mu$M) and nitroprusside (NP; 0.1mM), via the second messenger, cGMP, increase the feedback gain of BK$\rm\sb{Ca}$. In cell-attached patches bathed with physiological saline, these agents transiently activated BK$\rm\sb{Ca}$ from a basal $\rm P\sb{o}<0.05$ to peak responses near 0.50. As membrane potential hyperpolarizes towards $\rm E\sb{K}$ (2-3 minutes), BK$\rm\sb{Ca}$ inactivates. Upon depolarizing V$\rm\sb{m}$ with 140 mM KCl, db-cGMP (10$\mu$M) activated BK$\rm\sb{Ca}$ to a sustained P$\rm\sb{o}$ = 0.51. Addition of AII in the presence of cGMP further increased P$\rm\sb{o}$ to 0.82. Activation of BK$\rm\sb{Ca}$ by cGMP occured via an endogenous cGMP-dependent protein kinase (PKG): in excised, inside-out patches, PKG in the presence of Mg-ATP (0.1mM) and cGMP increased P$\rm\sb{o}$ from 0.07 to 0.39. In contrast, neither PKC nor PKA influenced BK$\rm\sb{Ca}$. Endogenous okadaic acid-sensitive protein phosphatase suppressed BK$\rm\sb{Ca}$ activity. Binning the change in P$\rm\sb{o}\ (\Delta P\sb{o}$) of BK$\rm\sb{Ca}$ in response to PKG (n = 69) established two distinct populations of channels: one that responded ($\cong$67%, $\rm\Delta P\sb{o} = 0.45 \pm 0.03$) and one that was unresponsive ($\Delta\rm P\sb{o} = 0.00 \pm 0.01$) to PKG. Activation of BK$\rm\sb{Ca}$ by PKG resulted from a decrease in the Ca$\sp{2+}$- and voltage-activation thresholds independent of sensitivities. In conclusion, mesangial BK$\rm\sb{Ca}$ channels sense both electrical and chemical signals of contraction and act as feedback regulators by repolarizing the plasma membrane. ANF and NO, via cGMP, stimulate endogenous PKG, which subsequently decreases the activation threshold of BK$\rm\sb{Ca}$ to increase the gain of this feedback regulatory signal. ^

Review of lattice results concerning low-energy particle physics

We review lattice results related to pion, kaon, D- and B-meson physics with the aim of making them easily accessible to the particle-physics community. More specifically, we report on the determination of the lightquark masses, the form factor f+(0), arising in semileptonic K → π transition at zero momentum transfer, as well as the decay-constant ratio fK / fπ of decay constants and its consequences for the CKM matrix elements Vus and Vud. Furthermore, we describe the results obtained on the lattice for some of the low-energy constants of SU(2)L × SU(2)R and SU(3)L×SU(3)R Chiral Perturbation Theory and review the determination of the BK parameter of neutral kaon mixing. The inclusion of heavy-quark quantities significantly expands the FLAG scope with respect to the previous review. Therefore, we focus here on D- and B-meson decay constants, form factors, and mixing parameters, since these are most relevant for the determination of CKM matrix elements and the global CKM unitarity-triangle fit. In addition we review the status of lattice determinations of the strong coupling constant αs.

Institutions for sustainable governance of forests: Equity, robustness and cross-level interactions in Mawlyngbna, Meghalaya, India

This study adopts Ostrom’s Social-Ecological Systems (SES) framework in empirical fieldwork to explain how local forestry institutions affect forest ecosystems and social equity in the community of Mawlyngbna in North-East India. Data was collected through 26 semi-structured interviews, participatory timeline development, policy documents, direct observation, periodicals, transect walks, and a concurrent forest-ecological study in the village. Results show that Mawlyngbna's forests provide important sources of livelihood benefits for the villagers. However, ecological disturbance and diversity varies among the different forest ownership types and forest-based livelihood benefits are inequitably distributed. Based on a bounded rationality approach, our analysis proposes a set of causal mechanisms that trace these observed social-ecological outcomes to the attributes of the resource system, resource units, actors and governance system. We analyse opportunities and constraints of interactions between the village, regional, and state levels. We discuss how Ostrom’s design principles for community-based resource governance inform the explanation of robustness but have a blind spot in explaining social equity. We report experiences made using the SES framework in empirical fieldwork. We conclude that mapping cross-level interactions in the SES framework needs conceptual refinement and that explaining social equity of forest governance needs theoretical advances.

Monitoring the temporal development of natural hazard risks as a basis indicator for climate change adaptation.

The potential effects of climatic changes on natural risks are widely discussed. But the formulation of strategies for adapting risk management practice to climate changes requires knowledge of the related risks for people and economic values. The main goals of this work were (1) the development of a method for analysing and comparing risks induced by different natural hazard types, (2) highlighting the most relevant natural hazard processes and related damages, (3) the development of an information system for the monitoring of the temporal development of natural hazard risk and (4) the visualisation of the resulting information for the wider public. A comparative exposure analysis provides the basis for pointing out the hot spots of natural hazard risks in the province of Carinthia, Austria. An analysis of flood risks in all municipalities provides the basis for setting the priorities in the planning of flood protection measures. The methods form the basis for a monitoring system that periodically observes the temporal development of natural hazard risks. This makes it possible firstly to identify situations in which natural hazard risks are rising and secondly to differentiate between the most relevant factors responsible for the increasing risks. The factors that most influence the natural risks could be made evident.

Expanded Clinical Spectrum of Multiple Evanescent White Dot Syndrome with Multimodal Imaging

PURPOSE: To evaluate and characterize multiple evanescent white dot syndrome abnormalities with modern multimodal imaging modalities. METHODS: This retrospective cohort study evaluated fundus photography, fluorescein angiography, indocyanine green angiography, optical coherence tomography, enhanced depth imaging optical coherence tomography, short-wavelength autofluorescence, and near-infrared autofluorescence. RESULTS: Thirty-four multiple evanescent white dot syndrome patients with mean age of 28.7 years were studied (range, 14-49 years). Twenty-six patients were women, and eight were men. Initial mean visual acuity was 0.41 logMAR. Final mean visual acuity was 0.03 logMAR. Fluorescein angiography shows a variable number of mid retinal early fluorescent dots distributed in a wreathlike pattern, which correlate to fundus photography, fundus autofluorescence, and indocyanine green angiography. Indocyanine green angiography imaging shows the dots and also hypofluorescent, deeper, and larger spots, which are occasionally confluent, demonstrating a large plaque of deep retinal hypofluorescence. Optical coherence tomography imaging shows multifocal debris centered at and around the ellipsoid layer, corresponding to the location of spots seen with photography, indocyanine green angiography, and fluorescein angiography. Protrusions of the hyperreflectant material from the ellipsoid layer toward the outer nuclear layer correspond to the location of dots seen with photography, indocyanine green angiography, and fluorescein angiography. CONCLUSION: Multimodal imaging analysis of the retina in patients with multiple evanescent white dot syndrome shows additional features that may help in the diagnosis of the disease and in further understanding its etiology. Multiple evanescent white dot syndrome is predominantly a disease of the outer retina, centered at the ellipsoid zone, but also involving the interdigitation zone and the outer nuclear layer.

Entwicklung und Implementierung von Modellen für ein Skills-Training-Parcours für internistische Assistenzärzte

„Entwicklung und Implementierung von Modellen für ein Skills-Training-Parcours für internistische Assistenzärzte “ V. Maier1 - K. Schnabel2 1 Universitätslinik für Allgemeine Innere Medizin, Inselspital, Bern 2 Berner interdisziplinäres Skills- und Schauspielpatientenzentrum (BiSS), Institut für Medizinische Lehre (IML), Abteilung für Unterricht und Medien (AUM) Einleitung: Im klinischen Alltag sind praktische Fertigkeiten gefordert, um Patienten sicher zu behandeln. Auch in der Schweizer Fachgesellschaft FMH kam es zu einer stärkeren Gewichtung der praktischen Fertigkeiten und müssen jetzt ein Logbuch über Art und Zeitpunkt der Intervention führen [1]. Am Inselspital Bern wurde dafür ein Skillsparcours etabliert, da in vielen Bereichen simulationsbasierte Ausbildungen traditionellen Methoden überlegen ist [2]. Der Skillsparcours besteht aus einem Nachmittag mit 4 nicht-invasiven Prozeduren und einem Nachmittag mit 5 invasiven Prozeduren. Eigens dafür wurden drei Modelle entwickelt und deren Tauglichkeit evaluiert. Fragestellung: Bilden die selbst gefertigten Modelle die Realität ausreichend ab? Material und Methoden: Innerhalb der 9 Posten (5 invasiv und 4 nichtinvasiv) wurden für die 5 invasiven Posten zwei Modelle aus dem Skillslab (BiSS) genutzt (Lumbalpunktion (LP) und Blasenkatheter (BK)) und drei Modelle neu entwickelt (Pleura-(PP), Aszites-(AP) und Knochenmarks-Punktion (KMP)). Die Modelle wurden mit Materialien aus dem Baumarkt entwickelt (Material ca. CHF 50/Stück). Der Aufbau der Modelle soll auf der Tagung demonstriert werden. Die Teilnehmer (N=12) und Dozenten (N=5) wurden zu der Qualität mittels Fragebogen befragt. Dabei wurde die individuelle Vorerfahrung und die Einschätzung der Teilnehmer erfragt. Die Frage zur Eignung des Modells war: „Das Modell war zum Üben geeignet“. Als Skala wurde eine Likert-Skala von 0 bis 5 (1=sehr ungeeignet, 5=sehr geeignet) benutzt. Ergebnisse: Die Assistenzärzte beurteilten die Modelleignung wie folgt (Median (Min;Max)): LP: 5 (4;5) KMP: 4.5 (3;5), PP: 4 (3;5), AP: 4.5 (2;5), BK-Einlage: 4.5 (4;6). Die Oberärzte, die jeweils nur das Modell bewerteten, an welchem sie den Kurs durchführten, beurteilten die Modelleignung wie folgt: LP 5.0, KMP: 5.0, PP 5.0, AP: 4.0, BK-Einlage: 3.0. Diskussion: Alle Modelle wurden sowohl von den Oberärzten als auch von den Assistenzärzten als zum Üben tauglich eingeschätzt. Zwischen den selbst hergestellten Low-Fidelity Modellen und den High-Fidelity Modellen gab es hierein keinen signifikanten Unterschied. Als am wenigsten tauglich wurde von den Oberärzten mit der Simulation der Blasenkatheter-Einlage ein High-Fidelity-Modell bewertet. Schlussfolgerungen: Alle Modelle für die Simulation der Punktionstechniken haben gut bis sehr gut funktioniert. Die selbst hergestellten Modelle bilden die Wirklich zum Üben der Techniken hinreichend gut und nicht schlechter als die High-Fidelity-Modelle ab. Selbst gebaute Modelle mit Materialien aus dem Baumarkt können das sonst sehr materialaufwändige Training mit Simulatoren genauso effektiv aber wesentlich effizienter durchführbar machen. Literatur bei den Autoren (1) Weiterbildungsordnung FMH 2014 (letzte Revision 4. September 2014). www.fmh.ch/files/pdf15/wbo_d.pdf (2) McGaghie WC, Issenberg SB, Cohen ER, Barsuk JH, Wayne DB (2011) Does simulation-based medical education with deliberate practice yield better results than traditional clinical education? A meta-analytic comparative review of the evidence. Acad Med. 2011 Jun;86(6):706-11

Évaluation: l’indépendance à l’épreuve de la relation entre mandants et mandataires

L’article suivant rend compte des résultats d’un atelier tenu à l’occasion du congrès 2015 de la SEVAL. L’atelier portait sur l’indépendance des évaluateurs et des évaluatrices du point de vue de leur relation avec les commanditaires de l’évaluation. Sur la base d’un exemple de mandat concret présenté par deux intervenants – l’évaluatrice ainsi que le conseiller d’État mandant de l’évaluation en question – les différents garde-fous contractuels, communicationnels et procéduraux aptes à garantir une pleine indépendance de l’évaluation ont été discutés. Il en est ressorti que quatre dimensions étaient cruciales pour le succès de la démarche : les conditions-cadres de l’évaluation, la récolte des données, les relations avec les évalués, ainsi que la phase de restitution des résultats.

Prevalence and risk factors for polyomavirus reactivation in solid-organ transplantation

Background. Polyomavirus reactivation is common in solid-organ transplant recipients who are given immunosuppressive medications as standard treatment of care. Previous studies have shown that polyomavirus infection can lead to allograft failure in as many as 45% of the affected patients. Hypothesis. Ubiquitous polyomaviruses when reactivated by post-transplant immunosuppressive medications may lead to impaired renal function and possibly lower survival prospects. Study Overview. Secondary analysis of data was conducted on a prospective longitudinal study of subjects who were at least 18 years of age and were recipients of liver and/or kidney transplant at Mayo Clinic Scottsdale, Arizona. Methods. DNA extractions of blinded urine and blood specimens of transplant patients collected at Mayo Clinic during routine transplant patient visits were performed at Baylor College of Medicine using Qiagen kits. Virologic assays included testing DNA samples for specific polyomavirus sequences using QPCR technology. De-identified demographic and clinical patient data were merged with laboratory data and statistical analysis was performed using Stata10. Results. 76 patients enrolled in the study were followed for 3.9 years post transplantation. The prevalence of BK virus and JC virus urinary excretion was 30% and 28%. Significant association was observed between JC virus excretion and kidney as the transplanted organ (P = 0.039, Pearson Chi-square test). The median urinary JCV viral loads were two logs higher than those of BKV. Patients that excreted both BKV and JCV appeared to have the worst renal function with a mean creatinine clearance value of 71.6 millimeters per minute. A survival disadvantage was observed for dual shedders of BKV and JCV, log-rank statistics, p = 0.09; 2/5 dual-shedders expired during the study period. Liver transplant and male sex were determined to be potential risk factors for JC virus activation in renal and liver transplant recipients. All patients tested negative for SV40 and no association was observed between polyomavirus excretion and type of immunosuppressive medication (tacrolimus, mycophenolate mofetil, cyclosporine and sirolimus). Conclusions. Polyomavirus reactivation was common after solid-organ transplantation and may be associated with impaired renal function. Male sex and JCV infection may be potential risk factors for viral reactivation; findings should be confirmed in larger studies.^

Concentrations of metals and POPs in liver tissue of wild sea bird chicks from the Norwegian arctic region

Lysosomal membrane stability, lipofuscin (LF), malondialdehyde (MDA), neutral lipid (NL) levels, as well as halogenated organic compounds (HOCs), Cr, Cd, Pb and Fe concentrations were analyzed in liver of black-legged kittiwake (BK), herring gull (HG), and northern fulmar (NF) chicks. There were significant species differences in the levels of NL, LF and lysosomal membrane stability. These parameters were not associated with the respective HOC concentrations. LF accumulation was associated with increasing Cr, Cd and Pb concentrations. HG presented the lowest lysosomal membrane stability and the highest. LF and NL levels, which indicated impaired lysosomes in HG compared to NF and BK. Lipid peroxidation was associated with HOC and Fe2+ levels. Specific HOCs showed positive and significant correlations with MDA levels in HG. The study indicates that contaminant exposure can affect lysosomal and lipid associated parameters in seabird chicks even at low exposure levels. These parameters may be suitable markers of contaminant induced stress in arctic seabirds.

Chemical composition of Fe-Mn nodules and crusts from oceans and seas

Fluorine concentrations were determined ionometrically with an error of 0.02% in iron-manganese materials of the ocean. They were: 0.02-0.04% in ocean iron-manganese nodules, with the exception of two specimens (0.08% and 0.20% F); up to 0.02% in iron-manganese nodules of seas; 0.02-1.17% in ore crusts from ocean seamounts; and 0.02% in ore sediments of the Red Sea. Elevated fluorine content of ore crusts is associated with presence of calcium phosphate inclusions in them. Fluorine is not accumulated during iron-manganese nodule mineralization. Its average concentration in the nodules is half that in host deep-sea sediments.