Renal protection in diabetes: lessons from ONTARGET®

Hypertension is an important independent risk factor for renal disease. If hypertension and chronic renal disease co-exist, as is common in patients with diabetes mellitus, the risk of cardiovascular disease is heightened. The importance of rigorous blood pressure control is recognized in current guidelines, with a recommended target of office blood pressure of < 130/80 mmHg; although ambulatory blood pressure may be more appropriate in order to identify the 24-hour hypertensive burden. Even lower blood pressure may further reduce the progression of chronic kidney disease, but the incidence of cardiovascular events may increase. Albuminuria not only indicates renal damage, but is also a powerful predictor of cardiovascular morbidity and mortality at least in patients with high cardiovascular risk and potentially pre-existing vascular damage. Management of the multiple factors for renal and cardiovascular disease is mandatory in the diabetic patient. The renin-angiotensin system (RAS) plays a pivotal role in the progression of renal disease, as well as in hypertension and target-organ damage. The use of agents that target the RAS confer renoprotection in addition to antihypertensive activity. There is extensive evidence of the renoprotective effect of angiotensin II receptor blockers (ARBs), and specifically telmisartan. In addition to providing 24-hour blood pressure control, clinical studies in patients with diabetes show that telmisartan improves renal endothelial function, prevents progression from microalbuminuria to macroalbuminuria, slows the decline in glomerular filtration rate and reduces proteinuria in overt nephropathy. These effects cannot be solely attributed to blood pressure control. In contrast to other members of the ARB class, the renoprotective effect of telmisartan is not confined to the management of diabetic nephropathy; slowing the progression of albuminuria has been demonstrated in the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET®), which included diabetic and non-diabetic patients at high risk of cardiovascular events

Factors Influencing Candidatesâ Choice of a Pediatric Dental Residency Program

The goal of this study was to identify the factors and program characteristics that influenced the program ranking decisions of applicants to pediatric dentistry residency programs. A questionnaire was sent to the firstâ year resident class in 2005 with a response rate of 69.2 percent (n=260). Approximately 55 percent were female (104/180) and 61 percent were nonâ Hisâ panic white (110/180). The respondents reported that they applied to an average of nine programs, of which five were ranked. Most applicants were interested in a program that had a hospital component with a duration of two years. A program’s ability to prepare the resident for an academic career was a minimal influence for 48.6 percent (87/179), and 57.5 percent (103/179) were not interested in a master’s or Ph.D. degree. Factors associated with program ranking included modern clinical facilities, high ratio of dental assistants and faculty to residents, availability of assistants for sedation and general anesthesia cases, availability of a salary or stipend, and amount of clinical experience. Important nonâ clinical factors included hospitality during the interview, geographic location, and perceived reputation of the program. Opportunity to speak with the current residents in private, observing the interaction between residents and faculty, and touring the facilities were also highly considered. These findings may help program directors tailor their interviews and programs to suit the needs of applicants.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153649/1/jddj002203372007719tb04384x.pd

Effects of erythropoietin therapy on the lipid profile in end-stage renal failure

Effects of erythropoietin therapy on the lipid profile in end-stage renal failure. To evaluate the effects of erythropoietin (EPO) therapy on the lipid profile in end-stage renal failure, we undertook a prospective study in patients on both hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). One hundred and twelve patients (81 HD, 31 CAPD) were enrolled into the study. Lipid parameters [that is, total cholesterol and the LDL and HDL subfractions, triglycerides, lipoprotein (a), apoproteins A and B], full blood count, iron studies, B12, folate, blood urea, aluminium and serum parathyroid hormone were measured prior to commencement of EPO therapy. Ninety-five patients were reassessed 5.2 ± 0.3 (mean ± SEM) months later and 53 patients underwent a further assessment 13.1 ± 0.6 months after the commencement of EPO, giving an overall follow-up of 10.0 ± 0.6 months in 95 patients. As expected, EPO treatment was associated with an increase in hemoglobin (7.7 ± 0.1 vs. 9.9 ± 0.2 g/dl; P < 0.001) and a decrease in ferritin (687 ± 99 vs. 399 ± 69 µg/liter; P < 0.01). A significant fall in total cholesterol occurred (5.8 ± 0.1 vs. 5.4 ± 0.2 mmol/liter; P < 0.05) in association with a fall in apoprotein B (1.15 ± 0.04 vs. 1.04 ± 0.06; P < 0.05) and serum triglycerides (2.26 ± 0.14 vs. 1.99 ± 0.21; P < 0.05) during the course of the study. Other lipid parameters did not change, although there was a trend towards improvement. These changes correlated with the increase in Hb (P < 0.001 in each case), and the reduction in ferritin for total cholesterol (P < 0.02), LDL cholesterol (P < 0.03), and to a lesser extent apoprotein B (P < 0.07). No difference was observed in patients using maintenance HD or CAPD, and similar trends were observed in male and female patients. Improvements in the lipid profile occurred independently of the time on dialysis prior to the commencement of EPO. We conclude that EPO treatment is associated with alterations in the lipid profile which may suggest a long-term improvement in the vascular morbidity of chronic renal failure. The causes of the improved lipids are not addressed by this study and may be equally due to a direct or secondary benefit of EPO therapy

Advance care planning in chronic kidney disease: a survey of current practice in Australia

Aim: Advance care planning (ACP) in nephrology is widely advocated but not always implemented. The aims of this study were to describe current ACP practice and identify barriers/facilitators and perceived need for health professional education and chronic kidney disease (CKD)-specific approaches. Methods: An anonymous cross-sectional survey was administered online. Nephrology health professionals in Australia and New Zealandwere recruited via professional societies, email lists and nephrology conferences. Multiple regression explored the influence of respondents’ attributes on extent of involvement in ACP and willingness to engage in future. Results: A total of 375 respondents included nephrologists (23%), nurses (65%), social workers (4%) and others (8%) with 54% indicated that ACP at their workplace was performed ad hoc and 61% poorly. Perceived barriers included patient/family discomfort (84%), difficulty engaging families (83%), lack of clinician expertise (83%) and time (82%), health professional discomfort (72%), cultural/language barriers (65%), lack of private space (61%) and lack of formal policy/procedures (60%). Respondents overwhelmingly endorsed the need for more dialysis-specific ACP programs (96%) and education (95%). Whilst 85% thought ACP would be optimally performed by specially trained staff, comments emphasized that all clinicians should have a working proficiency. Respondents who were more willing to engage in future ACP tended to be non-physicians (odds ratio (OR) 4.96, 95% confidence intervals (CI) 1.74–14.07) and reported a greater need for CKD-specific ACP materials (OR 10.88, 95% CI 2.38–49.79). Conclusion: Advance care planning in nephrology needs support through education and CKD-specific resources. Endorsement by nephrologists is important. A multidisciplinary approach with a gradient of ACP expertise is also recommended

Fascin 2b Is a Component of Stereocilia that Lengthens Actin-Based Protrusions

Stereocilia are actin-filled protrusions that permit mechanotransduction in the internal ear. To identify proteins that organize the cytoskeleton of stereocilia, we scrutinized the hair-cell transcriptome of zebrafish. One promising candidate encodes fascin 2b, a filamentous actin-bundling protein found in retinal photoreceptors. Immunolabeling of zebrafish hair cells and the use of transgenic zebrafish that expressed fascin 2b fused to green fluorescent protein demonstrated that fascin 2b localized to stereocilia specifically. When filamentous actin and recombinant fusion protein containing fascin 2b were combined in vitro to determine their dissociation constant, a Kd≈0.37 µM was observed. Electron microscopy showed that fascin 2b-actin filament complexes formed parallel actin bundles in vitro. We demonstrated that expression of fascin 2b or espin, another actin-bundling protein, in COS-7 cells induced the formation of long filopodia. Coexpression showed synergism between these proteins through the formation of extra-long protrusions. Using phosphomutant fascin 2b proteins, which mimicked either a phosphorylated or a nonphosphorylated state, in COS-7 cells and in transgenic hair cells, we showed that both formation of long filopodia and localization of fascin 2b to stereocilia were dependent on serine 38. Overexpression of wild-type fascin 2b in hair cells was correlated with increased stereociliary length relative to controls. These findings indicate that fascin 2b plays a key role in shaping stereocilia

Cofilin interacts with ClC-5 and regulates albumin uptake in proximal tubule cell lines

Receptor-mediated endocytosis is a constitutive high capacity pathway for the reabsorption of proteins from the glomerular filtrate by the renal proximal tubule. ClC-5 is a voltage-gated chloride channel found in the proximal tubule where it has been shown to be essential for protein uptake, based on evidence from patients with Dent's disease and studies in ClC-5 knockout mice. To further delineate the role of ClC-5 in albumin uptake, we performed a yeast two-hybrid screen with the C-terminal tail of ClC-5 to identify any interactions of the channel with proteins involved in endocytosis. We found that the C-terminal tail of ClC-5 bound the actin depolymerizing protein, cofilin, a result that was confirmed by GST-fusion pulldown assays. In cultured proximal tubule cells, cofilin was distributed in nuclear, cytoplasmic, and microsomal fractions and co-localized with ClC-5. Phosphorylation of cofilin by overexpressing LIM kinase 1 resulted in a stabilization of the actin cytoskeleton. Phosphorylation of cofilin in two proximal tubule cell models (porcine renal proximal tubule and opossum kidney) was also accompanied by a pronounced inhibition of albumin uptake. This study identifies a novel interaction between the C-terminal tail of ClC-5 and cofilin, an actin-associated protein that is crucial in the regulation of albumin uptake by the proximal tubule

Geological Field Trips

This field trip guide organized in the framework of the Goldschmidt Conference 2013, held in Florence from August 25 to 30, 2013, is here presented. The two-days field trip, shows some of the many geological, naturalistic and cultural features in the Fiorano area (Modena), in which history, geology and passion for Ferrari come together in a perfect marriage. The first excursion day is dedicated to visit the Natural Reserve of Salse di Nirano, where the mud volcanoes, produced by the cold mud, salt water and hydrocarbons - mainly methane- can be observed. The second day is devoted to visit the Ferrari Museum and goes on at the Spezzano Castle, hosting the Ceramics Museum. Clays are, in fact, abundant in the hilly margin, where they form badlands, characteristic narrow crests washed out by running waters. In the Castle there is also a Balsamic Vinegar producing Consortium, it’s a peculiar and typical product of Modena province. The itinerary ends with the tour to Enzo Ferrari’s Birthplace at Modena

Exploration of the altar painting “Sacra Conversazione” by Bernardino Licinio from the church of St. Francis in Krk

Slika Sacra Conversazione Bernardina Licinija iz crkve Sv. Franje Asiškog u Krku izrađena je tehnikom masne tempere na dasci. Velike dimenzije slike u kombinaciji sa smještajem na visini uz teška oštećenja nosioca i slikanih slojeva, zahtijevala su izvođenje konzervatorsko-restauratorskih istraživanja in situ. Tom je prilikom prvi put u Hrvatskoj izvan radionice, na terenu, primijenjena vizualizacija oltarne pale velikog formata računalnom radiografjom. Omogućila je uvid u stanje nosioca i slikanih slojeva, smanjila rizik demontaže i transporta te usmjerila daljnje konzervatorsko-restauratorske radove.The altar pala Sacra Conversazione, by Bernardino Licinio (Venice, 1485/1489–c. 1550), is located on the main altar of the Church of St. Francis in the town of Krk. It was painted in 1531 in tempera grassa on board. In contrast to the later Venetian Sacra Conversazione by the same artist, painted in 1535, the Krk pala is almost completely unknown in professional literature; it is mentioned only in some older literature, with a short iconographic description. Due to the painting’s large dimensions (280x195 cm) and weight, its location high on the main altar, and the significant damage to the painted layers, its wooden base and the support system, the conservation-restoration explorations were carried out in situ, at the church altar. This significantly reduced the possibility of additional damage being incurred during dismantling and transport. The artefact was filmed in the visible, UV and IR parts of the spectrum, and under slanted light. Samples of pigment and binding material were analysed in a laboratory, and the order of layers was established. A particularly interesting phase of the conservation-restoration exploration was the visualization of the artefact by computer radiography. This method, created and developed for medical purposes, is being applied ever more often in restoration for exploring and documenting artefacts. Prior to this occasion, it had not been used in Croatia for in situ explorations. The visualization of the Krk pala by computer radiography made it possible to assess the condition of the original painted layer, wooden base and support system, which is normally hidden by the large wall at the back of the altar. The computer radiography uncovered grave and extensive damage to the painting base and the painted layers, but which can be remedied and reconstructed. Exploratory attempts to remove the “secondary” coats from the surface of the original painted layer suggested that several interventions had already been made on the artefact, two of them rather substantial, and they included reduction of the altar painting’s format. The explorations carried out thus far have provided the basic information on this artefact, which will be supplemented by further restoration procedures, and archival and art-historical research